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US20120283117A1 - Determination of eosinophilic esophagitis - Google Patents

Determination of eosinophilic esophagitis Download PDF

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US20120283117A1
US20120283117A1 US13/412,469 US201213412469A US2012283117A1 US 20120283117 A1 US20120283117 A1 US 20120283117A1 US 201213412469 A US201213412469 A US 201213412469A US 2012283117 A1 US2012283117 A1 US 2012283117A1
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eotaxin
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Definitions

  • Eosinophilic esophagitis is an emerging worldwide disease, as documented by recent case series from Switzerland, Australia, Canada, Japan, England, and the U.S. Of concern, EE appears to be a growing health problem with an annual incidence of at least 1:10,000 children.
  • the primary symptoms of EE (chest and abdominal pain, dysphagia, heartburn, vomiting, and food impaction) are also observed in patients with chronic esophagitis (CE) including gastroesophageal reflux disease (GERD).
  • CE chronic esophagitis
  • GERD gastroesophageal reflux disease
  • EE poses considerable diagnostic and therapeutic challenges especially because esophageal eosinophilia has been associated with several other medical condition including GERD, parasitic infection, and hypereosinophilic syndromes.
  • EE In contrast to GERD, EE is more likely in males (80%), appears to have a not uncommon familial form, has a high rate of associated atopic disease (70%), and is typically not associated with abnormal pH probing of the esophagus. Distinguishing EE from GERD is important since EE patients typically do not respond to anti-GERD therapy, but rather respond to anti-inflammatory therapy and/or allergen elimination.
  • EE can be triggered by both food and aeroallergens, particularly when the esophageal disease is co-induced with respiratory inflammation.
  • nearly 25% of patients with EE are non-atopic individuals with no identifiable allergic sensitization.
  • a question is to understand the relationship between the atopic and non-atopic variants of EE; whether atopic and non-atopic esophagitis involves similar effector pathways has implications for therapeutic strategies.
  • Murine modeling has established that EE is a Th2 associated disease.
  • IL-5 is required for disease pathogenesis; a humanized anti-IL-5 appears to be effective in an early clinical study.
  • Human EE is associated with over-production of the Th2 cytokines IL-4 and IL-13.
  • Th2 cytokine have been implicated, the mechanism by which they lead to esophageal eosinophilia is unclear.
  • IL-4 and IL-13 are known to induce the eosinophil specific eotaxin chemokines (e.g. eotaxin-1, eotaxin-2, eotaxin-3), their role has remained elusive since they have yet been demonstrated to be over-produced in EE and eotaxin-1 deficient mice only develop a modest attenuation of experimental EE.
  • the inflamed esophagus may also involve a myriad of chemokines, with no dominance of a single chemokine.
  • Eosinophilic Esophagitis gene expression profiles and distinctions from chronic esophagitis (CE) are disclosed.
  • Whole genome wide expression analysis demonstrated an EE transcript signature that was similar across gender and patient age, but distinct from CE.
  • Atopic and non-atopic variants of EE had a conserved esophageal transciptome indicating overlapping effector pathways in the diseased tissue of these patients.
  • the most induced transcript in EE was eotaxin-3; levels of eotaxin-3 strongly correlated with disease severity and a single nucleotide polymorphism (SNP) in the eotaxin-3 gene conferred disease susceptibility. Protection from experimental EE was observed in mice harboring a genetic deletion in the eotaxin-3 receptor (CCR3).
  • CCR3 eotaxin-3 receptor
  • FIG. 1 shows the hierarchical cluster analysis of the transcripts expressed in normal (NL), chronic esophagitis (CE), and eosinophilic esophagitis (EE) esophageal biopsies.
  • RNA from each patient was subjected to chip analysis using Affymetrix Human Genome U133 GeneChip plus 2.
  • the NL group was composed of six individuals (1 to 6)
  • the CE group was composed of five individuals (7 to 11)
  • the EE group was composed of 13 individuals (12 to 24) (Table 2). 574 genes significantly expressed differently (p ⁇ 0.01) in EE compared to NL groups (Table 1).
  • FIG. 2 shows the EE transcript signature as a function of the allergic status and gender of EE individuals.
  • FIG. 3 shows the number of modified genes and their fold-change in EE and CE.
  • the average gene expression levels in EE and CE groups were compared to the average gene expression in the NL group.
  • the number of genes that changed 2-10-fold or more is shown.
  • the list of the 42 transcripts that was modified a ⁇ 10-fold in EE compared with NL groups, and their GeneBank accession number is shown.
  • FIG. 4 shows the correlation between eosinophil count and number of genes modified.
  • the numbers of genes expressed differently are presented as a function of eosinophil count (A).
  • A The number of genes that changed a ⁇ 5-fold (grey dot) or a ⁇ 10-fold (white dot) was plotted as a function of the maximum number of eosinophils in the biopsies.
  • a trendline black line
  • the histogram of the 1943 genes that most correlated (P ⁇ 0.005) to the number of eosinophils is presented (B).
  • Cluster analysis based on standard correlation tree ordered identified 4 groups (cluster A, B, C and D). The genes upregulated were represented in red and the downregulated genes were in blue. The magnitude of the gene changes was proportional to the darkness of the color.
  • FIG. 5 shows the quantitative analysis of eotaxin-1, -2 and -3 mRNA levels in NL, CE and EE groups using real-time PCR analysis.
  • the level of eotaxin-3 (A), eotaxin-1 (B) and eotaxin-2 (C) mRNA is shown.
  • Each mRNA value was normalized to GAPDH mRNA and expressed as fold change.
  • the black dash represented the average of fold change in each group.
  • the P value was calculated using the ANOVA test. The number of individuals was 6, 11 and 19 for NL, CE and EE groups respectively.
  • FIG. 6 shows the correlation between eotaxin-3 mRNA expression and esophageal eosinophil count.
  • FIG. 7 shows eotaxin-3 expression in the esophagus of EE individuals. Esophageal sections were subjected to in situ hybridization using the eotaxin-3 anti-sense probe.
  • the hybridization signal of the eotaxin-3 anti-sense (AS) and sense (S) probe are shown in an esophageal EE patient biopsy (a, b, c, d, e, f and g).
  • Brightfield (a, c, d, e and f) and darkfield images (b and g) are shown at 40 ⁇ (a, b, f and g) and 100 ⁇ (c, d and e) magnification.
  • the darkfield signal is white/pink and the brightfield signal is black.
  • arrows show the epithelial eotaxin-3 expression.
  • the hybridization of the S probe to the same biopsies is shown in f and g.
  • FIG. 8 shows blood eotaxin-3 protein levels. Eotaxin-3 level in plasma was assessed by ELISA. Each data point represented the eotaxin-3 level in one individual. The NL and EE groups are each composed of 9 individuals. P value was calculated using ANOVA.
  • FIG. 9 shows the role of CCR3 in allergen-induced eosinophil recruitment to the esophagus of wild type (WT) and CCR3 deficient (knockout (KO)) mice.
  • FIG. 10 shows a schematic representation of EE transcript signature in an EE esophageal biopsy.
  • 574 genes defined the EE transcript signature, including cytokines, mast cell genes, arachidonic acid metabolism genes, and others.
  • a proposed model to explain eotaxin-3-associated eosinophil recruitment in EE is shown.
  • Hyperplasic epithelial cells of the esophagus overexpress eotaxin-3.
  • Eotaxin-3 overexpression allows eosinophil chemoattraction of due to the CCR3 receptor.
  • Eotaxin-3 protein leaks in the blood and may be used as a biomarker of EE.
  • SNPs in eotaxin-3 may contribute to modify expression, or of the eotaxin-3 RNA or the affinity of eotaxin-3 protein for its receptor.
  • Other SNPs e.g., CCR3 receptor
  • Mast cells are also recruited in the esophagus and mast cell genes (tryptase and carboxypeptidase) are overrepresented in the EE transcript signatures. Mast cells and eosinophils degranulations lead to tissue damage.
  • Esophageal eosinophilia with dysphagia A distinct clinicopathologic syndrome. Dig Dis Sci 38:109; Fox et al., 2002, Eosinophilic esophagitis: it's not just kid's stuff. Gastrointest Endosc 56:26, each of which is expressly incorporated by reference herein in its entirety.
  • Normal individuals served as a control and were defined as having 0 eosinophils/hpf and no basal layer expansion.
  • Individuals with chronic esophagitis (CE) were defined as having mild expansion of the basal layer (about ⁇ 1 ⁇ 3 of epithelium) and/or 23 eosinophils/hpf.
  • Individuals with eosinophilic esophagitis (EE) were defined by >24 eosinophils/hpf and extensive basal layer hyperplasia (expansion to about >1 ⁇ 3 of epithelium).
  • RNAlater RNA Stabilization reagent Qiagen, Germany
  • Total RNA was extracted using RNAeasy mini Kit (Qiagen) according to the manufacturer's recommendations.
  • Hybridization to DNA microarrays was performed by the Gene Chip Core at Children's Hospital Medical Center, Cincinnati Ohio.
  • RNA quality was first assessed using the Agilent bioanalyzer (Agilent Technologies, Palo Alto, Calif.) (verifying high quality spectophometric characteristics), converted to cDNA with Superscript and subsequently converted to biotinylated cRNA with Enzo high yield RNA transcript labeling.
  • microarrays After hybridization to the genome wide human Affymetrix U133A plus 2.0 genechips, the microarrays were stained with streptavidin-phycoerythrin using a Fluidics Station (Affymetix). The microarrays were scanned with a Hewlett Packard GeneArray Scanner, and gene transcript levels were determined using algorithms in the Microarray Analysis Suite and GeneSpring software (Silicon Genetics, Redwood City Calif.).
  • Differentially expressed transcripts were subjected to gene ontology analysis using DAVID (database for annotation, visualization and integrated discovery) and EASE (expression analysis systematic explorer), which is a web-based (http://david.niaid.nih.qov/david/upload.asp) client/server application that allowed users to access a relational database of functional annotation.
  • DAVID database for annotation, visualization and integrated discovery
  • EASE expression analysis systematic explorer
  • esophageal biopsy samples were fixed in 4% paraformaldehyde/PBS and stored overnight at 4° C. and subsequently emerged in 30% sucrose before in situ hybridization was performed.
  • eotaxin-3 cDNA was generated using the primers acctgagaagggcctgattt and gtaactctgggaggaaacaccctctc and cloned into PCR2.2 vector (Invitrogen).
  • the resulting plasmid was linearized by BamHI or XhoI digestion, and sense and antisense RNA probes, respectively, were generated by T7 and sp6 RNA polymerase (Riboprobe Gemini Core System II transcription kit; Invitrogen.
  • the radiolabeled ( ⁇ 35SthioUTP) probes were hybridized and the slides were washed under high stringency conditions. The slides were washed at 65° C.
  • RNA samples 500 ng were subjected to reverse transcription analysis using Bioscript reverse transcriptase (BioRad) according to manufacturer's instructions.
  • Eotaxin-1, -2 and -3 were quantified by real-time PCR using the LightCycler instrument and LightCycler FastStart.
  • DNA master SYBR green 1 as a ready-to use reaction mix (Roche, Indianapolis, Ind.) according to manufacturer's instructions. Results were normalized to GAPDH amplified from the same cDNA mix time and expressed as fold induction compared to controls.
  • cDNA were amplified using following primers: hEotaxin-3(151 bp): aactccgaaacaattgtactcagctg and gtaactctgggaggaaacaccctctcc; hEotaxin-2(251 bp): ccatagtaaccagccttc and caggttcttcatgtacctc; hEotaxin-1(425 bp):tgaagcttgggccagcttctgtcccaacc and ggtcgactggagttggagatttttggtc; GAPDH(400 bp): tggaaatcccatcaccatct and gtcttctgggtggcagtgat.
  • Plasma from heparinized blood was extracted and eotaxin-3 in 100 ⁇ l of plasma was quantified using Quantikine kit CCL26 (R&D Systems, Minneapolis) according to manufacturer's instructions. Results were expressed as pg of eotaxin-3 per ml plasma. The detection of the ELISA was 7 pg/ml.
  • Primers were designed using commercial software (Roche) and PCR was performed using LightCyler FastStart DNA master Hybridization Probes (Roche) according to manufacturer's protocol using the eotaxin-3 specific primers: aaggaaaaatgggtgca and tgaacaacctttattaaagtaactct.
  • the anchor probe was labeled with LCred fluorophore linked to agccaagagcggggtcc.
  • the sensor probe gcgtcctcggatgacaattca
  • Primers were designed using Primer Design Software (Roche).
  • mice National Cancer Institute, Frederick Md.
  • CCR3-deficient mice BALB/c background; a gift of Drs. Alison Humbles and Craig Gerard, Harvard Medical School
  • Experimental EE was induced by exposing mice to Aspergillus fumigatus antigen intranasally three times a week for 3 weeks. Mice were sacrificed 48 h following the last challenge, and the esophagus was harvested and fixed in formalin.
  • Eosinophil levels were determined by immunostaining for mouse eosinophil major basic protein (anti-MBP), as disclosed in Mishra et al., 2001, An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest 107:83, which is expressly incorporated by reference herein in its entirety. Briefly, endogenous peroxidases in the tissues were quenched with 0.3% hydrogen peroxide in methanol followed by pepsin digestion for 5 min and by nonspecific protein blocking with normal goat serum for 30 min at room temperature. Tissue sections were then incubated with rabbit anti-MBP (a gift of Dr.
  • anti-MBP mouse eosinophil major basic protein
  • Genes listed on microarray were obtained by studying differences in genes expression level between groups using Welch T-Test and Student T test (with or without false rate discovery (FDR) correction). EE transcripts were obtained using Welch T test with FDR (p ⁇ 0.01). CE transcript signature was composed of the addition of the gene lists from Welch T test without FDR and genes from Student T-test without FDR (p ⁇ 0.01). Ordered tree clustering was performed using standard correlation and distance. Correlation of gene expression with numeric clinical parameters or eosinophil levels was assessed using Pearson Correlation Test with p value. Tests used to generate the gene lists and number of genes in these lists are shown in Table 5. These lists were filtered based on p value and/or fold changes. Statistical significance between two groups of data was determined using T test or ANOVA, and correlations of data with number of eosinophils in the biopsies were determined using Pearson Correlation Test with p value.
  • the association between the SNP 2497T>G and EE susceptibility was first examined by family-based transmission disequilibrium test (TDT) to determine whether the affected child received the disease-associated allele more frequently than the alternative allele.
  • TDT/S-TDT 1.1 http://qenomics.med.upenn.edu/spielman/TDT.htm
  • Statistical significance was evaluated by exact test using shuffling method, generated by 10 4 random permutations of the data.
  • Hardy-Weinberg equilibrium test was also conducted in cases and controls, respectively.
  • the software HWE http://linkage.rockefeller.edu/ott/linkutil.htm) was used to compute chi-square test for deviations from Hardy-Weinberg equilibrium.
  • EE transcript signatures were determined. Esophageal biopsy samples derived from individual patients were subjected to whole genome wide transcript expression profile analysis using oligonucleotide-based DNA microarray chips (Affymetrix Human Genome U133 GeneChip plus 2). Of the 54,681 transcripts represented on these microarrays, 574 transcripts (Table 1) were differently expressed (p ⁇ 0.01) in the EE versus NL biopsy samples; thus, about 1% of the whole human genome transcripts defined the EE transcript signature, also referred to as the EE transcriptome, the complete collection of transcribed elements in the genome. For the EE and/or CE transcriptomes, this includes all transcribed elements related to these diseases. Besides mRNAs, it includes non-coding structural and regulatory RNAs.
  • RNAs or translated proteins can contribute to pathogeneisis.
  • Hierarchical clustering of the signal intensities of the individual transcripts in each group showed a high similarity of transcript expression patterns between EE patients ( FIG. 1A ). Of these, 344 transcripts were expressed more abundantly and 230 were expressed less abundantly in EE compared to NL individuals ( FIG. 1A ).
  • Gene ontology analysis of the EE transcript signature revealed that the over-expressed genes were frequently involved in cell communication (25%), signal transduction (21%), response to external stimulus (20%), immune response (16%), and response to stress (11%). In contrast, the down-regulated genes were composed of a distinct family of functional groups (Table 4).
  • mast cell genes While there were numerous related families of dysregulated genes, five mast cell genes were highly induced, including carboxypeptidase A3, high affinity IgE receptor (Fc ⁇ RI), and mast cell tryptase alpha (Table 9). Arachadonic acid metabolism genes were also represented; there were several dysregulated genes including the upregulated 15-lipoxygenase, prostaglandin D2 synthetase, leukotriene A4 hydrolase, and the down regulated 12-lipoxygenase, prostaglandin F synthase, leukotriene B4 12-hydroxydehydrogenase (Table 8). Regulators of cell growth and maintenance (periostin, fibroblast growth factor 11, Gro1 alpha) were over-represented (Tables 3 and 4).
  • Cluster analysis was performed to stratify dynamic genes into related subgroups ( FIG. 1B ). Clusters 4 and 5 represented downregulated and upreglated genes, respectively, compared with NL and CE individuals. Cluster analysis identified that CE also had a unique transcript signature compared with NL individuals; cluster 1 represented genes upregulated in CE compared to NL individuals.
  • the identification of an EE transcript signature provided insight into disease pathogenesis. It was determined whether the allergic and non-allergic EE variants had different transcript profiles. When the full EE transcript profile was compared between allergic and non-allergic EE patients, there was near complete overlap in the transcripts ( FIG. 2A ) of the EE signature genome defined in Table 1. Only two genes were differently expressed (Lymphocyte Antigen 75 (2-fold increase in atopic) and Secreted Frizzled-related protein-1 (1.8-fold increase in non-atopic). The human LY75 molecule has previously been shown to have effect on IL-4 signaling. It was determined if EE patients had age dependent variable gene expression. Of the 574 dysregulated transcripts, no gene correlated with patient age within the EE transcript profile.
  • Transcript expression profiles were compared in patients who presented with symptoms of EE but were found to have CE.
  • Esophageal samples from CE patients contained only 216 dynamic transcripts (Table 5), about 0.4% of the tested genome, compared with NL (p ⁇ 0.01).
  • FIG. 1B the CE transcripts are seen in clusters 1, 2 and 3. These 216 transcripts (108 over expressed shown in combined clusters 1 and 2 and 108 down regulated in cluster 3) were rich in genes involved in intracellular cascades (10%) and biosynthesis (10%) (both in cluster 1) and cell growth and maintenance (22%) (in cluster 2).
  • No transcript was modified by z 5-fold in CE compared to NL ( FIG. 3 ).
  • 124 genes were modified by 5-fold in EE compared with NL ( FIG.
  • FIG. 3 including 42 transcripts that were modified 10-fold in EE; the most dysregulated genes are shown in FIG. 3 .
  • EE and CE transcriptomes were directly compared. There was an overlap of only 40 genes between EE and CE (mainly in cluster 2) ( FIG. 1B and Table 6) and only 5 of these overlapped with the EE transcript signature. All genes shared between EE and CE were modified by ⁇ 2-fold compared to NL samples. Taken together, EE and CE did not appear to represent a continuum, but rather two distinct disease processes. Identification of strongly induced genes that distinguished EE from CE ( FIG. 3 ) defined potential diagnostic criteria to distinguish these forms of esophagitis.
  • the EE transcriptome was analyzed as a function of disease severity, because that the number and magnitude of modified genes might be directly related to disease severity. Correlation of eosinophil levels with the number of altered genes was determined. Individuals with EE had eosinophil levels that varied between 24 to 218 eosinophils/hpf. The number of dysregulated genes increased between eosinophils levels of 0 and 56 and reached a plateau at eosinophil levels of 77 ( FIGS. 1 & 4A ). Similarly, the magnitude of genes changes (e.g. their degree of change) directly correlated with eosinophil levels ( FIG. 4 ).
  • Cluster B included genes that correlated with eosinophil level that were overexpressed in patients with 24 eosinophils/hpf and were frequently involved in cell communication (25%) and immune response (13%) functions.
  • Cluster A contained genes that correlated with higher eosinophil levels 40 eosinophils/hpf). Cluster A was particularly rich in genes involved in cell growth and maintenance (24%). The mast cell gene signature was located in cluster B, which suggested that mast cells infiltration occurred as soon as 24 eosinophils/hpf were present in the esophagus.
  • eotaxin-3 protein level in the plasma was quantified in NL and EE patients.
  • a 2-fold increase in eotaxin-3 protein levels was observed between NL and EE plasma samples ( FIG. 8 ).
  • Eotaxin-3 protein levels were 65 ⁇ 17 and 30 ⁇ 13 pg/ml in EE and NL plasma samples, respectively (P ⁇ 0.002).
  • No significant difference was observed in the eotaxin-3 level in the blood between allergic and non-allergic patients (64 ⁇ 19 and 61 ⁇ 26 pg/ml respectively).
  • Eotaxin-3 was implicated in the disease pathogenesis of EE, so that single nucleotide polymorphisms (SNP) in the eotaxin-3 gene might be associated with disease risk.
  • SNP single nucleotide polymorphisms
  • the presence of eotaxin-3 +2496 (G/T) SNP in EE patients compared with control individuals was examined.
  • the wild type allele is T having a frequency of 78.81% in control individuals.
  • the G allele was over-represented in EE patients compared with NL (Table 7).
  • the GG was strongly associated with EE (GG frequency was 13.54% and 2.26% in EE and NL, respectively).
  • the relative risk of EE in patients with the GG allele was about 7-fold.
  • the G and T alleles were inherited based on Hardy-Weinberg equilibrium (Table 7).
  • CCR3 gene target mice were protected from experimental EE.
  • a murine system was used to evaluate the eotaxin pathway directly in vivo.
  • An experimental model of EE had been developed, but an exact homolog of human eotaxin-3 had not yet been characterized in mice, therefore induction of experimental asthma in mice deficient in the eotaxin receptor CCR3 was examined.
  • Cohorts of wild type and CCR3 deficient mice were exposed to repeated doses of intranasal allergen under conditions that induce experimental EE.
  • large numbers of eosinophils accumulated in the esophagus.
  • CCR3 deficient mice were nearly completely protected from developing esophageal eosinophilia ( FIG. 9 ).
  • EE transcript signature involving about 1% of the human genome. This transcriptome was conserved between individuals despite their age, gender, atopic status, and the patchiness of their disease. Despite the presence of apparent atopic and nonatopic EE variants of, the downstream effector phase of the disease was conserved between these disease variants rather than a large variability in gene transcript levels between patients due to their divergent clinical presentations (including age and gender). Thus, despite millions of SNPs in the human genome, EE and perhaps others polygenic disorders may have largely conserved disease mechanisms.
  • results are consistent with analysis of atopic and non-atopic variants of eosinophilic lung disease (asthma); while these only examined a limited set of cytokine mRNA levels, atopic and non-atopic patients had the same cytokine mRNA expression in lung tissue.
  • the present data evidenced that atopic and non-atopic variants of eosinophilic disorders have a common underlying pathogenesis.
  • a method of examining the etiology of atopic and disease variants is presented.
  • Eotaxin-3 which regulates eosinophil responses in vitro, was the top gene induced in EE. Levels of eotaxin-3 strongly correlated with disease severity and served as a disease biomarker. Mice with genetic deletion of the CCR3 eotaxin-3 receptor were protected from developing experimental EE. The specific overexpression of eotaxin-3, and not eotaxin-1 or eotaxin-2, was consistent with prior studies showing only modest protection from experimental EE in eotaxin-1 deficient mice, and the absence of eotaxin-1 overexpression in EE patients.
  • Eotaxin-2 and -3 mRNA levels both contain Th2-associated STATE binding sites in their promoters. While all eotaxins bind to CCR3, they each have a different affinity for recombinant CCR3; EE patients may also have preferential responses to individual eotaxins. Without being bound by a specific theory, this may be due to specific SNPs in CCR3. A specific genetic variation in the eotaxin-3 gene was a strong risk factor for EE.
  • SNP While this SNP was in a non-coding region of the eotaxin-3 gene, it might be in linkage disequilibrium with a functional SNP; this SNP is 6 kp from SNP-4097 (rs7787623) in the promoter region, these two SNP appear to be in total linkage disequilibrium.
  • the SNP+2496 has been associated with atopy in the Korean population. However, in the Caucasian population, this SNP was at a higher frequency (21% vs 5% allele frequency in Caucasians and Koreans, respectively). This genetic finding may be used alone or in combination with other markers, including eotaxin-3 protein levels, to establish non-invasive ways of assessing disease risk and/or phenotype.
  • CE also had its own unique transcript signature.
  • the CE pathology was typical of GERD and was likely applicable to GERD. Identified transcript changes should be correlated with esophageal pH monitoring. GERD has not yet been analyzed by DNA microarray analysis. While there was a degree of overlap in CE and EE genes, there was a difference in the number of genes modified, the type of dysregulated genes, and the magnitude of the gene changes. Taken together, the data demonstrated that EE and CE were separate diseases, and were unlikely to represent a continuum of esophagitis. The results provide diagnostic criteria for distinguishing EE from other types of esophagitis. Levels of the genes listed in FIG. 3 may be disease determinants.
  • Mast cells were involved in EE based on the dominant mast cell gene signature in microarray analysis. Mast cell genes were upregulated when eosinophil levels were 24 eosinophils/hpf suggesting that mast cells correlated with eosinophils. Mast cells have been reported to be elevated in the esophagus of EE patients, although no assessment of their genetic content or phenotype was made. The finding of tryptase expression without chymase suggested the involvement of T cell dependent mucosal mast cells. Anti-mast cell therapy may be used for reducing, amelorating, or treating EE.
  • CLC Charcot Leyden Crystal
  • CLC protein often crystallizes in the lung, yet such crystals have not yet been seen in EE.
  • Other genes were involved in the EE transcript signature ( FIG. 10 ).
  • periostin a gene that is strongly over-expressed (47-fold) in EE patients, has been associated with epithelial cell growth, angiogenesis, and cellular adhesion.
  • Cadherin-26 (over-expressed by 23-fold in EE patients) is a member of the cadherin family that has been associated with a variety of inflammatory and epithelial proliferation diseases.
  • the most down-regulated gene, CRISP-3 cyste-rich secretory protein-3) is an androgen-dependent transcript, perhaps linking the male gender association with EE.
  • EE may be an eotaxin-3 dominant disease involving a conserved genetic transcript signature ( FIG. 10 ).
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Abstract

Eosinophilic esophagitis (EE), an emerging disorder with poorly understood pathogenesis, was examined. Esophageal tissue was analyzed by a genome wide microarray expression analysis. EE patients had a transcript signature involving 1% of the genome that was conserved across gender, age, and atopic status, and was distinct from that associated with chronic esophagitis (CE). The eosinophil specific chemokine eotaxin-3 was the top induced gene compared with normal controls. Levels C of eotaxin-3 mRNA and protein correlated with disease severity. A single nucleotide polymorphism in the human eotaxin-3 gene conferred susceptibility to disease. Mice deficient in the eotaxin-3 receptor (CCR-3) were protected from experimental EE. Eotaxin-3 was identified as a specific effector molecule, biomarker, and genetic risk factor for EE, and distinguished EE from CE.

Description

    RELATED APPLICATION
  • This application claims priority from U.S. Provisional Application Ser. No. 60/633,909 filed Dec. 7, 2004, which is expressly incorporated by reference herein.
  • The U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of Grant Nos. RO1 A145898 and R24 DK0064403 awarded by the National Institutes of Health.
    • BACKGROUND
  • Eosinophilic esophagitis (EE) is an emerging worldwide disease, as documented by recent case series from Switzerland, Australia, Canada, Japan, England, and the U.S. Of concern, EE appears to be a growing health problem with an annual incidence of at least 1:10,000 children. The primary symptoms of EE (chest and abdominal pain, dysphagia, heartburn, vomiting, and food impaction) are also observed in patients with chronic esophagitis (CE) including gastroesophageal reflux disease (GERD). EE poses considerable diagnostic and therapeutic challenges especially because esophageal eosinophilia has been associated with several other medical condition including GERD, parasitic infection, and hypereosinophilic syndromes. In contrast to GERD, EE is more likely in males (80%), appears to have a not uncommon familial form, has a high rate of associated atopic disease (70%), and is typically not associated with abnormal pH probing of the esophagus. Distinguishing EE from GERD is important since EE patients typically do not respond to anti-GERD therapy, but rather respond to anti-inflammatory therapy and/or allergen elimination. Whereas both GERD and EE are associated with esophageal eosinophils, the level of eosinophils in EE is much higher; it has been proposed that the diagnosis of EE requires greater than 24 eosinophils per high-powered field (×40) from an esophageal tissue biopsy since these levels have been associated with non-responsiveness to anti-GERD therapy. However, whether GERD and EE representative a continuum, with EE being a more severe manifestation has not been addressed. A more clear differentiation between these various esophagitis states is needed.
  • Experimental dissection of experimental EE models in mice have revealed that EE can be triggered by both food and aeroallergens, particularly when the esophageal disease is co-induced with respiratory inflammation. However, nearly 25% of patients with EE are non-atopic individuals with no identifiable allergic sensitization. A question is to understand the relationship between the atopic and non-atopic variants of EE; whether atopic and non-atopic esophagitis involves similar effector pathways has implications for therapeutic strategies. Murine modeling has established that EE is a Th2 associated disease. IL-5 is required for disease pathogenesis; a humanized anti-IL-5 appears to be effective in an early clinical study. Human EE is associated with over-production of the Th2 cytokines IL-4 and IL-13. However, although these Th2 cytokine have been implicated, the mechanism by which they lead to esophageal eosinophilia is unclear. While IL-4 and IL-13 are known to induce the eosinophil specific eotaxin chemokines (e.g. eotaxin-1, eotaxin-2, eotaxin-3), their role has remained elusive since they have yet been demonstrated to be over-produced in EE and eotaxin-1 deficient mice only develop a modest attenuation of experimental EE. Based on homology with allergic inflammation in the lung, which involves the interplay of at least 17 chemokines including all three eotaxins, the inflamed esophagus may also involve a myriad of chemokines, with no dominance of a single chemokine.
    • SUMMARY OF THE INVENTION
  • Eosinophilic Esophagitis (EE) gene expression profiles and distinctions from chronic esophagitis (CE) are disclosed. Expression profiling of esophageal biopsy tissue from patients with EE compared to patients with CE, as well as healthy controls was performed. Whole genome wide expression analysis demonstrated an EE transcript signature that was similar across gender and patient age, but distinct from CE. Atopic and non-atopic variants of EE had a conserved esophageal transciptome indicating overlapping effector pathways in the diseased tissue of these patients. The most induced transcript in EE was eotaxin-3; levels of eotaxin-3 strongly correlated with disease severity and a single nucleotide polymorphism (SNP) in the eotaxin-3 gene conferred disease susceptibility. Protection from experimental EE was observed in mice harboring a genetic deletion in the eotaxin-3 receptor (CCR3).
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 shows the hierarchical cluster analysis of the transcripts expressed in normal (NL), chronic esophagitis (CE), and eosinophilic esophagitis (EE) esophageal biopsies. RNA from each patient was subjected to chip analysis using Affymetrix Human Genome U133 GeneChip plus 2. The NL group was composed of six individuals (1 to 6), the CE group was composed of five individuals (7 to 11), and the EE group was composed of 13 individuals (12 to 24) (Table 2). 574 genes significantly expressed differently (p<0.01) in EE compared to NL groups (Table 1). 574 genes significantly expressed differently (p<0.01) in EE compared to NL groups, and 228 genes significantly expressed differently (p<0.01) in CE compared to NL group. The data were analyzed by cluster analysis and ordered (standard correlation (A) and distance (B)) using Genespring software. Cluster 1, 2 and 3 highlight the CE transcripts and cluster 4 and 5 highlight the EE transcripts. The down regulated genes were depicted in blue and up-regulated genes were in red. The magnitude of the gene change was proportional to the darkness of the color. Each column represented a separate individual and each line a gene.
  • FIG. 2 shows the EE transcript signature as a function of the allergic status and gender of EE individuals. The 574 genes of the EE signature were subjected to cluster analysis and ordered (standard correlation) using Genespring software. Average expression of the transcripts of the EE signature was depicted in the non-allergic (n=4) and allergic EE (n=9) (A), and in the female (n=5) and male EE individuals (n=8) (B).
  • FIG. 3 shows the number of modified genes and their fold-change in EE and CE. The average gene expression levels in EE and CE groups were compared to the average gene expression in the NL group. The number of genes that changed 2-10-fold or more is shown. The list of the 42 transcripts that was modified a ≧10-fold in EE compared with NL groups, and their GeneBank accession number is shown.
  • FIG. 4 shows the correlation between eosinophil count and number of genes modified. The numbers of genes expressed differently are presented as a function of eosinophil count (A). The number of genes that changed a ≧5-fold (grey dot) or a ≧10-fold (white dot) was plotted as a function of the maximum number of eosinophils in the biopsies. A trendline (black line) has been inserted to show the genes that change a ≧10-fold. The histogram of the 1943 genes that most correlated (P≦0.005) to the number of eosinophils is presented (B). Cluster analysis based on standard correlation tree ordered identified 4 groups (cluster A, B, C and D). The genes upregulated were represented in red and the downregulated genes were in blue. The magnitude of the gene changes was proportional to the darkness of the color.
  • FIG. 5 shows the quantitative analysis of eotaxin-1, -2 and -3 mRNA levels in NL, CE and EE groups using real-time PCR analysis. The level of eotaxin-3 (A), eotaxin-1 (B) and eotaxin-2 (C) mRNA is shown. Each mRNA value was normalized to GAPDH mRNA and expressed as fold change. The black dash represented the average of fold change in each group. The P value was calculated using the ANOVA test. The number of individuals was 6, 11 and 19 for NL, CE and EE groups respectively.
  • FIG. 6 shows the correlation between eotaxin-3 mRNA expression and esophageal eosinophil count. The eotaxin-3 expression measured using LightCycler (black dots and black line) and microarray analysis (open squares and dash line) was plotted as a function of the maximum eosinophil number (cells/hpf) present in the biopsies of NL, CE and EE individuals.
  • FIG. 7 shows eotaxin-3 expression in the esophagus of EE individuals. Esophageal sections were subjected to in situ hybridization using the eotaxin-3 anti-sense probe. The hybridization signal of the eotaxin-3 anti-sense (AS) and sense (S) probe are shown in an esophageal EE patient biopsy (a, b, c, d, e, f and g). Brightfield (a, c, d, e and f) and darkfield images (b and g) are shown at 40× (a, b, f and g) and 100× (c, d and e) magnification. The darkfield signal is white/pink and the brightfield signal is black. In the paired dark and bright field photomicrographs arrows show the epithelial eotaxin-3 expression. The hybridization of the S probe to the same biopsies is shown in f and g.
  • FIG. 8 shows blood eotaxin-3 protein levels. Eotaxin-3 level in plasma was assessed by ELISA. Each data point represented the eotaxin-3 level in one individual. The NL and EE groups are each composed of 9 individuals. P value was calculated using ANOVA.
  • FIG. 9 shows the role of CCR3 in allergen-induced eosinophil recruitment to the esophagus of wild type (WT) and CCR3 deficient (knockout (KO)) mice. Mice were challenged with saline or Aspergillus intranasally three times a week for three weeks. The esophagus was harvested 24 h after the last intranasal treatment and esophageal sections were stained with anti-MBP. Results represent the number of eosinophils (mean±SD) (n=3) present in the esophagus per mm2 of two representative experiments. *P<0.05 versus saline group, §P<0.05 versus WT group.
  • FIG. 10 shows a schematic representation of EE transcript signature in an EE esophageal biopsy. 574 genes defined the EE transcript signature, including cytokines, mast cell genes, arachidonic acid metabolism genes, and others. Without being limited to a specific mechanism, a proposed model to explain eotaxin-3-associated eosinophil recruitment in EE is shown. Hyperplasic epithelial cells of the esophagus overexpress eotaxin-3. Eotaxin-3 overexpression allows eosinophil chemoattraction of due to the CCR3 receptor. Eotaxin-3 protein leaks in the blood and may be used as a biomarker of EE. SNPs in eotaxin-3 may contribute to modify expression, or of the eotaxin-3 RNA or the affinity of eotaxin-3 protein for its receptor. Other SNPs (e.g., CCR3 receptor) may be involved. Mast cells are also recruited in the esophagus and mast cell genes (tryptase and carboxypeptidase) are overrepresented in the EE transcript signatures. Mast cells and eosinophils degranulations lead to tissue damage.
    •  DETAILED DESCRIPTION
  • Individual characteristics are provided in Table 2. None of the patients were taking glucocorticoids (topical or oral) at the time of the endoscopy. Patient biopsies, collected from the distal esophagus during routine endoscopy following informed consent, were submerged in formalin for routine pathological analysis with hematoxylin and eosin staining. Diagnosis was established based on the maximum eosinophil count per high power field (hpf) and basal layer expansion according to established criteria. (eg. Rothenberg et al., 2001, Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin Immunol 108:891; Attwood et al., 1993. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 38:109; Fox et al., 2002, Eosinophilic esophagitis: it's not just kid's stuff. Gastrointest Endosc 56:26, each of which is expressly incorporated by reference herein in its entirety. Normal individuals (NL) served as a control and were defined as having 0 eosinophils/hpf and no basal layer expansion. Individuals with chronic esophagitis (CE) were defined as having mild expansion of the basal layer (about <⅓ of epithelium) and/or 23 eosinophils/hpf. Individuals with eosinophilic esophagitis (EE) were defined by >24 eosinophils/hpf and extensive basal layer hyperplasia (expansion to about >⅓ of epithelium).
  • To assess allergen sensitization. skin prick testing was performed to a panel of 11 aeroallergens and 63 food antigens and assessed based on a 0-4 scale by comparison to the histamine control response. The total number of positive reactions to allergens (food allergen and aeroallergen) were counted and re-scored on a 0-4 scale. A score of 0-3 corresponded to 0, 1, 2, and 3 positive prick reactions, respectively; a score of 4 corresponded to z 4 positive prick responses. Patients with a score of 1 were considered atopic.
  • For DNA microarray analysis, for each patient, one distal biopsy sample was emerged in RNAlater RNA Stabilization reagent (Qiagen, Germany) and stored at 4° C. for <15 days. Total RNA was extracted using RNAeasy mini Kit (Qiagen) according to the manufacturer's recommendations. Hybridization to DNA microarrays was performed by the Gene Chip Core at Children's Hospital Medical Center, Cincinnati Ohio. In brief, after RNA extraction, RNA quality was first assessed using the Agilent bioanalyzer (Agilent Technologies, Palo Alto, Calif.) (verifying high quality spectophometric characteristics), converted to cDNA with Superscript and subsequently converted to biotinylated cRNA with Enzo high yield RNA transcript labeling. After hybridization to the genome wide human Affymetrix U133A plus 2.0 genechips, the microarrays were stained with streptavidin-phycoerythrin using a Fluidics Station (Affymetix). The microarrays were scanned with a Hewlett Packard GeneArray Scanner, and gene transcript levels were determined using algorithms in the Microarray Analysis Suite and GeneSpring software (Silicon Genetics, Redwood City Calif.).
  • Differentially expressed transcripts were subjected to gene ontology analysis using DAVID (database for annotation, visualization and integrated discovery) and EASE (expression analysis systematic explorer), which is a web-based (http://david.niaid.nih.qov/david/upload.asp) client/server application that allowed users to access a relational database of functional annotation.
  • For in situ hybridization, esophageal biopsy samples were fixed in 4% paraformaldehyde/PBS and stored overnight at 4° C. and subsequently emerged in 30% sucrose before in situ hybridization was performed. In brief, eotaxin-3 cDNA was generated using the primers acctgagaagggcctgattt and gtaactctgggaggaaacaccctctcc and cloned into PCR2.2 vector (Invitrogen). The resulting plasmid was linearized by BamHI or XhoI digestion, and sense and antisense RNA probes, respectively, were generated by T7 and sp6 RNA polymerase (Riboprobe Gemini Core System II transcription kit; Invitrogen. The radiolabeled (α35SthioUTP) probes were hybridized and the slides were washed under high stringency conditions. The slides were washed at 65° C. for 30 min in 50% formamide/1×SSC (150 mM NaCl/15 mM sodium citrate)/10 mM DTT; rinsed three times in 500 mM NaCl/10 mM Tris HCI, pH 7.5/5 mM EDTA; digested with RNase A for 30 min at 37° C.; and rinsed in fresh buffer. The high-stringency wash was repeated and then followed by two 15-min washes at room temperature, one in 1×SSC and one in 0.1×SSC/1 mM DTT. Autoradiography was performed for 2-4 weeks at 4° C. Hybridization specificity was established by using the eotaxin-3 sense riboprobe. Sections from NL, EE and CE individuals were hybridized and underwent autoradiography under identical conditions.
  • For real-time polymerase chain reaction (PCR) analysis, RNA samples (500 ng) were subjected to reverse transcription analysis using Bioscript reverse transcriptase (BioRad) according to manufacturer's instructions. Eotaxin-1, -2 and -3 were quantified by real-time PCR using the LightCycler instrument and LightCycler FastStart. DNA master SYBR green 1 as a ready-to use reaction mix (Roche, Indianapolis, Ind.) according to manufacturer's instructions. Results were normalized to GAPDH amplified from the same cDNA mix time and expressed as fold induction compared to controls. cDNA were amplified using following primers: hEotaxin-3(151 bp): aactccgaaacaattgtactcagctg and gtaactctgggaggaaacaccctctcc; hEotaxin-2(251 bp): ccatagtaaccagccttc and caggttcttcatgtacctc; hEotaxin-1(425 bp):tgaagcttgggccagcttctgtcccaacc and ggtcgactggagttggagatttttggtc; GAPDH(400 bp): tggaaatcccatcaccatct and gtcttctgggtggcagtgat.
  • Plasma from heparinized blood was extracted and eotaxin-3 in 100 μl of plasma was quantified using Quantikine kit CCL26 (R&D Systems, Minneapolis) according to manufacturer's instructions. Results were expressed as pg of eotaxin-3 per ml plasma. The detection of the ELISA was 7 pg/ml.
  • Buccal swab DNA was collected from EE individuals (n=96) and their immediate relatives and from non-EE individuals (n=177) following informed consent. DNA was isolated by alkaline extraction. SNP detection was accessed using LightCycler'instrument (Roche, Indianapolis). Briefly, LightCycler melting curves analysis was based on discriminating the temperature-dependant hybridization of sequence-specific hybridization probes to single-stranded DNA. Primers were designed using commercial software (Roche) and PCR was performed using LightCyler FastStart DNA master Hybridization Probes (Roche) according to manufacturer's protocol using the eotaxin-3 specific primers: aaggaaaaaatgggtgca and tgaacaacctttattaaagtaactct. For eotaxin-3 SNP analysis, the anchor probe was labeled with LCred fluorophore linked to agccaagagcggggtcc. The sensor probe (gcgtcctcggatgacaattca) was labeled with a second fluorophore (fluorescein) and designed to span the G/T mutation. Primers were designed using Primer Design Software (Roche).
  • BALB/c mice (National Cancer Institute, Frederick Md.) and CCR3-deficient mice (BALB/c background; a gift of Drs. Alison Humbles and Craig Gerard, Harvard Medical School) were housed under specific pathogen-free conditions. Experimental EE was induced by exposing mice to Aspergillus fumigatus antigen intranasally three times a week for 3 weeks. Mice were sacrificed 48 h following the last challenge, and the esophagus was harvested and fixed in formalin. Eosinophil levels were determined by immunostaining for mouse eosinophil major basic protein (anti-MBP), as disclosed in Mishra et al., 2001, An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest 107:83, which is expressly incorporated by reference herein in its entirety. Briefly, endogenous peroxidases in the tissues were quenched with 0.3% hydrogen peroxide in methanol followed by pepsin digestion for 5 min and by nonspecific protein blocking with normal goat serum for 30 min at room temperature. Tissue sections were then incubated with rabbit anti-MBP (a gift of Dr. James Lee, Mayo Clinic, Scottsdale Ariz.) (1:10,000) for 1 h at 4° C., followed by a 1:1000 dilution of biotinylated goat anti-rabbit IgG secondary antibody for 30 min at room temperature. Negative controls were assessed by replacing the primary antibody with normal rabbit serum to check endogenous biotin and peroxidase activity. Then avidin-peroxidase complex (Vector Laboratories, Burlingame Calif.) was used for 30 minutes. Immunoreactive cells quantification was carried out by a video-assistant integrated computer software program (Image Pro Plus 4.1; Media Cytometrics, Silver Spring Md.). Eosinophil levels were expressed as cells/mm2.
  • Genes listed on microarray were obtained by studying differences in genes expression level between groups using Welch T-Test and Student T test (with or without false rate discovery (FDR) correction). EE transcripts were obtained using Welch T test with FDR (p≦0.01). CE transcript signature was composed of the addition of the gene lists from Welch T test without FDR and genes from Student T-test without FDR (p≦0.01). Ordered tree clustering was performed using standard correlation and distance. Correlation of gene expression with numeric clinical parameters or eosinophil levels was assessed using Pearson Correlation Test with p value. Tests used to generate the gene lists and number of genes in these lists are shown in Table 5. These lists were filtered based on p value and/or fold changes. Statistical significance between two groups of data was determined using T test or ANOVA, and correlations of data with number of eosinophils in the biopsies were determined using Pearson Correlation Test with p value.
  • The association between the SNP 2497T>G and EE susceptibility was first examined by family-based transmission disequilibrium test (TDT) to determine whether the affected child received the disease-associated allele more frequently than the alternative allele. The software TDT/S-TDT 1.1 (http://qenomics.med.upenn.edu/spielman/TDT.htm) was used for analysis. Next, a case-control comparison was conducted at both genotype and allele frequency levels, where the cases are from the proband of each family, a set of race/ethnicity matched unrelated normal individuals were collected as controls. Statistical significance was evaluated by exact test using shuffling method, generated by 104 random permutations of the data. Hardy-Weinberg equilibrium test was also conducted in cases and controls, respectively. The software HWE (http://linkage.rockefeller.edu/ott/linkutil.htm) was used to compute chi-square test for deviations from Hardy-Weinberg equilibrium.
  • EE transcript signatures were determined. Esophageal biopsy samples derived from individual patients were subjected to whole genome wide transcript expression profile analysis using oligonucleotide-based DNA microarray chips (Affymetrix Human Genome U133 GeneChip plus 2). Of the 54,681 transcripts represented on these microarrays, 574 transcripts (Table 1) were differently expressed (p<0.01) in the EE versus NL biopsy samples; thus, about 1% of the whole human genome transcripts defined the EE transcript signature, also referred to as the EE transcriptome, the complete collection of transcribed elements in the genome. For the EE and/or CE transcriptomes, this includes all transcribed elements related to these diseases. Besides mRNAs, it includes non-coding structural and regulatory RNAs. Alterations in the structure or expression levels of any one of these RNAs or translated proteins can contribute to pathogeneisis. Hierarchical clustering of the signal intensities of the individual transcripts in each group showed a high similarity of transcript expression patterns between EE patients (FIG. 1A). Of these, 344 transcripts were expressed more abundantly and 230 were expressed less abundantly in EE compared to NL individuals (FIG. 1A). Gene ontology analysis of the EE transcript signature (Table 3) revealed that the over-expressed genes were frequently involved in cell communication (25%), signal transduction (21%), response to external stimulus (20%), immune response (16%), and response to stress (11%). In contrast, the down-regulated genes were composed of a distinct family of functional groups (Table 4).
  • While there were numerous related families of dysregulated genes, five mast cell genes were highly induced, including carboxypeptidase A3, high affinity IgE receptor (Fc□RI), and mast cell tryptase alpha (Table 9). Arachadonic acid metabolism genes were also represented; there were several dysregulated genes including the upregulated 15-lipoxygenase, prostaglandin D2 synthetase, leukotriene A4 hydrolase, and the down regulated 12-lipoxygenase, prostaglandin F synthase, leukotriene B4 12-hydroxydehydrogenase (Table 8). Regulators of cell growth and maintenance (periostin, fibroblast growth factor 11, Gro1 alpha) were over-represented (Tables 3 and 4).
  • To further analyze the EE transcript signature, cluster analysis was performed to stratify dynamic genes into related subgroups (FIG. 1B). Clusters 4 and 5 represented downregulated and upreglated genes, respectively, compared with NL and CE individuals. Cluster analysis identified that CE also had a unique transcript signature compared with NL individuals; cluster 1 represented genes upregulated in CE compared to NL individuals.
  • The identification of an EE transcript signature provided insight into disease pathogenesis. It was determined whether the allergic and non-allergic EE variants had different transcript profiles. When the full EE transcript profile was compared between allergic and non-allergic EE patients, there was near complete overlap in the transcripts (FIG. 2A) of the EE signature genome defined in Table 1. Only two genes were differently expressed (Lymphocyte Antigen 75 (2-fold increase in atopic) and Secreted Frizzled-related protein-1 (1.8-fold increase in non-atopic). The human LY75 molecule has previously been shown to have effect on IL-4 signaling. It was determined if EE patients had age dependent variable gene expression. Of the 574 dysregulated transcripts, no gene correlated with patient age within the EE transcript profile. As a control, outside of the EE transcript signature, there were 334 genes that correlated to patient age (Pearson correlation test with p<0.01). It was determined if the EE transcript profile was different between males and females. Only one gene (tyrosine kinase receptor B (3-fold increase in females) of the EE transcript signature depended upon gender (FIG. 2B). Outside of the EE transcript signature, there were 434 different genes between male and female EE. These results demonstrated that the EE transcript profile was conserved between individuals despite differences in gender, age, and atopic status.
  • Transcript expression profiles were compared in patients who presented with symptoms of EE but were found to have CE. Esophageal samples from CE patients contained only 216 dynamic transcripts (Table 5), about 0.4% of the tested genome, compared with NL (p<0.01). In FIG. 1B, the CE transcripts are seen in clusters 1, 2 and 3. These 216 transcripts (108 over expressed shown in combined clusters 1 and 2 and 108 down regulated in cluster 3) were rich in genes involved in intracellular cascades (10%) and biosynthesis (10%) (both in cluster 1) and cell growth and maintenance (22%) (in cluster 2). No transcript was modified by z 5-fold in CE compared to NL (FIG. 3). In contrast, 124 genes were modified by 5-fold in EE compared with NL (FIG. 3), including 42 transcripts that were modified 10-fold in EE; the most dysregulated genes are shown in FIG. 3. To define genes that could distinguish EE and CE, EE and CE transcriptomes were directly compared. There was an overlap of only 40 genes between EE and CE (mainly in cluster 2) (FIG. 1B and Table 6) and only 5 of these overlapped with the EE transcript signature. All genes shared between EE and CE were modified by <2-fold compared to NL samples. Taken together, EE and CE did not appear to represent a continuum, but rather two distinct disease processes. Identification of strongly induced genes that distinguished EE from CE (FIG. 3) defined potential diagnostic criteria to distinguish these forms of esophagitis.
  • The EE transcriptome was analyzed as a function of disease severity, because that the number and magnitude of modified genes might be directly related to disease severity. Correlation of eosinophil levels with the number of altered genes was determined. Individuals with EE had eosinophil levels that varied between 24 to 218 eosinophils/hpf. The number of dysregulated genes increased between eosinophils levels of 0 and 56 and reached a plateau at eosinophil levels of 77 (FIGS. 1 & 4A). Similarly, the magnitude of genes changes (e.g. their degree of change) directly correlated with eosinophil levels (FIG. 4). The genes that most correlated (P<0.005) with eosinophil levels are presented in an ordered tree histogram and stratified into cluster A, B and C (FIG. 4B). Cluster B included genes that correlated with eosinophil level that were overexpressed in patients with 24 eosinophils/hpf and were frequently involved in cell communication (25%) and immune response (13%) functions. Cluster A contained genes that correlated with higher eosinophil levels 40 eosinophils/hpf). Cluster A was particularly rich in genes involved in cell growth and maintenance (24%). The mast cell gene signature was located in cluster B, which suggested that mast cells infiltration occurred as soon as 24 eosinophils/hpf were present in the esophagus. Within the EE transcript signature, the gene with greatest change was eotaxin-3, which was induced 53-fold. Other relevant eosinophil chemokines, such as eotaxin-1 and eotaxin-2, were induced <2-fold in EE samples. Using real time PCR analysis (Lightcycler), a mean 53-fold increase in eotaxin-3 mRNA compared with NL was observed (FIG. 5A). Modest changes in eotaxin-1 (FIG. 5B) and eotaxin-2 (FIG. 5C) were observed in EE patients, although there was some variability between patients. Elevated levels of eotaxin-2 and eotaxin-3 correlated with each other (P<0.05). Correlation between the level of eotaxin-3 and eosinophil levels in esophageal samples was determined. Two methods (Lightcycler quantification and microarray analysis) revealed a strong correlation between eotaxin-3 and eosinophil counts (P<0.01) (FIG. 6).
  • To localize eotaxin-3 production in the esophagus, in situ hybridization was performed on esophageal biopsies with eotaxin-3 sense and anti-sense cRNA probes. In EE patients, eotaxin-3 anti-sense probe strongly stained the epithelial cell layer (FIG. 7). Brightfield microscopy revealed that eotaxin-3 positive cells were confined to a population of mononuclear cells within the epithelial layer most consistent with epithelial cells. Infiltrative eosinophils were eotaxin-3 negative. Hybridization of eotaxin-3 anti-sense probes to NL and CE samples and the eotaxin-3 sense probe to EE samples revealed no significant staining (data not shown).
  • To determine whether eotaxin-3 could be used as a non-invasive biomarker, eotaxin-3 protein level in the plasma was quantified in NL and EE patients. A 2-fold increase in eotaxin-3 protein levels was observed between NL and EE plasma samples (FIG. 8). Eotaxin-3 protein levels were 65±17 and 30±13 pg/ml in EE and NL plasma samples, respectively (P<0.002). No significant difference was observed in the eotaxin-3 level in the blood between allergic and non-allergic patients (64±19 and 61±26 pg/ml respectively).
  • Eotaxin-3 was implicated in the disease pathogenesis of EE, so that single nucleotide polymorphisms (SNP) in the eotaxin-3 gene might be associated with disease risk. The presence of eotaxin-3 +2496 (G/T) SNP in EE patients compared with control individuals was examined. The wild type allele is T having a frequency of 78.81% in control individuals. The G allele was over-represented in EE patients compared with NL (Table 7). The GG was strongly associated with EE (GG frequency was 13.54% and 2.26% in EE and NL, respectively). The relative risk of EE in patients with the GG allele was about 7-fold. In both EE and NL individuals, the G and T alleles were inherited based on Hardy-Weinberg equilibrium (Table 7).
  • CCR3 gene target mice were protected from experimental EE. A murine system was used to evaluate the eotaxin pathway directly in vivo. An experimental model of EE had been developed, but an exact homolog of human eotaxin-3 had not yet been characterized in mice, therefore induction of experimental asthma in mice deficient in the eotaxin receptor CCR3 was examined. Cohorts of wild type and CCR3 deficient mice were exposed to repeated doses of intranasal allergen under conditions that induce experimental EE. In wild type mice, large numbers of eosinophils accumulated in the esophagus. While, CCR3 deficient mice were nearly completely protected from developing esophageal eosinophilia (FIG. 9).
  • The data reported above identified an EE transcript signature involving about 1% of the human genome. This transcriptome was conserved between individuals despite their age, gender, atopic status, and the patchiness of their disease. Despite the presence of apparent atopic and nonatopic EE variants of, the downstream effector phase of the disease was conserved between these disease variants rather than a large variability in gene transcript levels between patients due to their divergent clinical presentations (including age and gender). Thus, despite millions of SNPs in the human genome, EE and perhaps others polygenic disorders may have largely conserved disease mechanisms. The results are consistent with analysis of atopic and non-atopic variants of eosinophilic lung disease (asthma); while these only examined a limited set of cytokine mRNA levels, atopic and non-atopic patients had the same cytokine mRNA expression in lung tissue. The present data evidenced that atopic and non-atopic variants of eosinophilic disorders have a common underlying pathogenesis. A method of examining the etiology of atopic and disease variants is presented.
  • Eotaxin-3, which regulates eosinophil responses in vitro, was the top gene induced in EE. Levels of eotaxin-3 strongly correlated with disease severity and served as a disease biomarker. Mice with genetic deletion of the CCR3 eotaxin-3 receptor were protected from developing experimental EE. The specific overexpression of eotaxin-3, and not eotaxin-1 or eotaxin-2, was consistent with prior studies showing only modest protection from experimental EE in eotaxin-1 deficient mice, and the absence of eotaxin-1 overexpression in EE patients. Correlation of eotaxin-2 and -3 mRNA levels with each other was consistent with their common chromosomal location (7q11.23), suggesting co-regulation and co-involvement in EE. Eotaxin-2 and eotaxin-3 both contain Th2-associated STATE binding sites in their promoters. While all eotaxins bind to CCR3, they each have a different affinity for recombinant CCR3; EE patients may also have preferential responses to individual eotaxins. Without being bound by a specific theory, this may be due to specific SNPs in CCR3. A specific genetic variation in the eotaxin-3 gene was a strong risk factor for EE. While this SNP was in a non-coding region of the eotaxin-3 gene, it might be in linkage disequilibrium with a functional SNP; this SNP is 6 kp from SNP-4097 (rs7787623) in the promoter region, these two SNP appear to be in total linkage disequilibrium. The SNP+2496 has been associated with atopy in the Korean population. However, in the Caucasian population, this SNP was at a higher frequency (21% vs 5% allele frequency in Caucasians and Koreans, respectively). This genetic finding may be used alone or in combination with other markers, including eotaxin-3 protein levels, to establish non-invasive ways of assessing disease risk and/or phenotype.
  • CE also had its own unique transcript signature. The CE pathology was typical of GERD and was likely applicable to GERD. Identified transcript changes should be correlated with esophageal pH monitoring. GERD has not yet been analyzed by DNA microarray analysis. While there was a degree of overlap in CE and EE genes, there was a difference in the number of genes modified, the type of dysregulated genes, and the magnitude of the gene changes. Taken together, the data demonstrated that EE and CE were separate diseases, and were unlikely to represent a continuum of esophagitis. The results provide diagnostic criteria for distinguishing EE from other types of esophagitis. Levels of the genes listed in FIG. 3 may be disease determinants.
  • Mast cells were involved in EE based on the dominant mast cell gene signature in microarray analysis. Mast cell genes were upregulated when eosinophil levels were 24 eosinophils/hpf suggesting that mast cells correlated with eosinophils. Mast cells have been reported to be elevated in the esophagus of EE patients, although no assessment of their genetic content or phenotype was made. The finding of tryptase expression without chymase suggested the involvement of T cell dependent mucosal mast cells. Anti-mast cell therapy may be used for reducing, amelorating, or treating EE.
  • Few eosinophil-derived molecules were present in the EE transcript signature. For example, CCR3 and MBP were not in the EE transcript signature despite the eosinophil infiltration. This may be due to the dilution of eosinophil transcripts with transcripts from relative RNA-rich cells such as epithelial cells, fibroblasts and mast cells. However, Charcot Leyden Crystal (CLC) mRNA, an eosinophil specific transcript, was overexpressed in EE. CLC protein was initially reported to possess weak lysophospholipase activity. It showed no sequence similarities to any known lysophospholipases, but was a potent epithelial cell cytotoxin. CLC protein often crystallizes in the lung, yet such crystals have not yet been seen in EE. Other genes were involved in the EE transcript signature (FIG. 10). For example, periostin, a gene that is strongly over-expressed (47-fold) in EE patients, has been associated with epithelial cell growth, angiogenesis, and cellular adhesion. Cadherin-26 (over-expressed by 23-fold in EE patients) is a member of the cadherin family that has been associated with a variety of inflammatory and epithelial proliferation diseases. The most down-regulated gene, CRISP-3 (cysteine-rich secretory protein-3) is an androgen-dependent transcript, perhaps linking the male gender association with EE. In EE patient biopsies, there was a dysregulation in genes involved in arachadonic acid metabolism (e.g. upregulation of cyclooxygenase-2 and 15-lipoxygenase and downregulation of cyclooxygenase-1 and 12-lipoxygenase). Cox1 deficient mice developed increased levels of Th2 cytokines (IL-4, IL-13, and 5) and had higher recruitment of eosinophils following allergen challenge. In the gastrointestinal tract, cycloxygenase-2 had a role in epithelial cell growth.
  • Without being limited by a specific theory, EE may be an eotaxin-3 dominant disease involving a conserved genetic transcript signature (FIG. 10). The modulation of esophageal genes, compared with CE, supports that EE was a primary esophageal disease. Based on these results, eotaxin-3 and/or CCR3 blockers may be beneficial for the treatment of EE.
  • TABLE 1
    EE Transcriptome
    Genbank
    Fold Accession SEQ
    Common Name Description Change number ID NO
    CCL26 ||MIP-4alpha||CCL26||TSC- 53.17 NM_006072 1
    1||SCYA26, FORMERLY||eotaxin-3
    precursor||EOTAXIN 3||CC
    chemokine IMAC||thymic stroma
    chemokine-1||macrophage
    inflammatory protein 4-alpha||small
    inducible cytokine
    A26||CHEMOKINE, CC MOTIF,
    LIGAND 26||chemokine (C-C motif)
    ligand 26||SMALL INDUCIBLE
    CYTOKINE SUBFAMILY A, MEMBER
    26, FORMERLY||small inducible
    cytokine subfamily A (Cys-Cys),
    member 26||
    POSTN ||OSF-2||POSTN||PN||periostin, 46.29 NM_006475 2
    osteoblast specific factor||osteoblast
    specific factor 2 (fasciclin I-like)||
    TNFAIP6 ||TSG6||TNFAIP6||hyaluronate- 23.59 NM_007115 3
    binding protein||tumor necrosis
    factor-stimulated gene-6
    protein||TUMOR NECROSIS
    FACTOR-ALPHA-INDUCED PROTEIN
    6||tumor necrosis factor-inducible
    protein 6||tumor necrosis factor,
    alpha-induced protein 6||tumor
    necrosis factor alpha-inducible
    protein 6||tumor necrosis factor,
    alpha-induced protein 6 precursor||
    CDH26 ||CDH26||cadherin-like 26|| 23.42 NM_177980 4
    CDH26 ||CDH26||cadherin-like 26|| 21 NM_177980 5
    ALOX15 ||1.13.11.33||ALOX15||arachidonate 20.89 NM_001140 6
    15-lipoxygenase||15-
    @LIPOXYGENASE, RETICULOCYTE
    ARACHIDONATE||
    PMCH ||PMCH||pro-melanin-concentrating 19.01 NM_002674 7
    hormone||
    CXCL1 ||MGSA-a||NAP- 18.79 NM_001511 8
    3||CXCL1||SCYB1||GROa||GRO1,
    FORMERLY||GRO PROTEIN,
    ALPHA||GRO1 ONCOGENE,
    FORMERLY||MELANOMA GROWTH
    STIMULATORY ACTIVITY,
    ALPHA||GRO1 oncogene (melanoma
    growth-stimulating
    activity)||CHEMOKINE, CXC MOTIF,
    LIGAND 1||GRO1 oncogene
    (melanoma growth stimulating
    activity, alpha)||SMALL INDUCIBLE
    CYTOKINE SUBFAMILY B, MEMBER
    1||chemokine (C—X—C motif) ligand 1
    (melanoma growth stimulating
    activity, alpha)||
    IGLV@ ||IGLJ3||immunoglobulin lambda 17.57 AK057174 9
    joining 3||
    IGHD ||IGHM||immunoglobulin 16.42 AK090461 10
    mu||IMMUNOGLOBULIN HEAVY MU
    CHAIN||immunoglobulin heavy
    constant mu||constant region of
    heavy chain of IgM||
    FLJ16025 FLJ16025 15 XM_293626 11
    UBD ||UBD||FAT10||diubiquitin||ubiquitin 14.85 NM_006398 12
    D||
    IGJ ||IGCJ||JCH||IGJ||immunoglobulin J 14.61 NM_144646 13
    chain||immunoglobulin J
    polypeptide, linker protein for
    immunoglobulin alpha and mu
    polypeptides||
    FLJ33069 ||FLJ33069||hypothetical protein 14.01 NM_144649 14
    FLJ33069||
    CPA3 ||CPA3||3.4.17.1||carboxypeptidase 13.13 NM_001870 15
    A3 (mast cell)||CARBOXYPEPTIDASE
    A3, MAST CELL||mast cell
    carboxypeptidase A3 precursor||
    CLC ||LPPL_HUMAN||CLC||galactin- 12.69 NM_001828 16
    10||3.1.1.5||LGALS10||GALECTIN
    10||lysolecithin
    acylhydrolase||eosinophil
    lysophospholipase||LYSOPHOSPHOLIPASE
    OF EOSINOPHIL||Charot-
    Leyden crystal protein||Charcot-
    Leyden crystal protein||
    TCF12; HEB; IGKC 12.64 BX647333 17
    HTF4; HsT17266
    IGL@ IGL 12.4 NG_000002 18
    PHLDB2 ||PHLDB2||pleckstrin homology-like 12.05 NM_145753 19
    domain, family B, member 2||
    POSTN ||OSF-2||POSTN||PN||periostin, 11.84 NM_006475 20
    osteoblast specific factor||osteoblast
    specific factor 2 (fasciclin I-like)||
    TCF12; HEB; IGKC 10.97 BX647333 21
    HTF4; HsT17266
    FLJ23259 ||FLJ23259||hypothetical protein 10.94 NM_024727 22
    FLJ23259||
    TCF12; HEB; IGKC 10.2 BX647333 23
    HTF4; HsT17266
    EPPK1 ||EPIPL1||EPPK1||epiplakin 1||450 kDa 10.12 NM_031308 24
    epidermal antigen||
    na ||||Hypothetical LOC148280 9.701 XM_097433 25
    (LOC148280), mRNA||
    SLC26A4 ||SLC26A4||pendrin||PDS||DFNB4|| 9.548 NM_000441 26
    solute carrier family 26, member 4||
    EPPK1 ||EPIPL1||EPPK1||epiplakin 1||450 kDa 9.334 NM_031308 27
    epidermal antigen||
    CTSC ||HMS||CPPI||3.4.14.1||DPPI||PALS 9.008 NM_001814 28
    ||DPP1||CTSC||PLS||dipeptidyl
    transferase||cathepsin C||dipeptidyl-
    peptidase I||cathepsin J||Papillon-
    Lefevre syndrome||DIPEPTIDYL
    PEPTIDASE I||cathepsin C isoform b
    precursor||cathepsin C isoform a
    preproprotein||
    SAMSN1 ||HACS1||SAMSN1||HEMATOPOIETIC 8.687 NM_022136 29
    ADAPTOR CONTAINING SH3 AND
    SAM DOMAINS 1||SAM domain, SH3
    domain and nuclear localisation
    signals, 1||SAM DOMAIN, SH3
    DOMAIN, AND NUCLEAR
    LOCALIZATION SIGNALS 1||
    TRPM6 ||CHAK2||TRPM6||CHANNEL KINASE 8.519 NM_017662 30
    2||transient receptor potential
    cation channel, subfamily M,
    member 6||
    IGLV@ IGL 8.317 AK057174 31
    SEC6L1 ||||SEC6L1||SEC6-like 1 (S. cerevisiae) 8.068 NM_007277 32
    ||
    GPR160 ||GPCR150||GPR160||putative G 8.008 NM_014373 33
    protein-coupled receptor||G protein-
    coupled receptor 160||
    SUSD2 ||SUSD2||sushi domain containing 8.003 NM_019601 34
    2||
    KIAA0495 ||KIAA0495|| 7.996 AB007964 35
    NTRK2 ||TRKB||NTRK2||TYROSINE KINASE 7.355 NM_006180 36
    RECEPTOR B||neurotrophic tyrosine
    kinase, receptor, type 2||
    CTSC ||HMS||CPPI||3.4.14.1||DPPI||PALS 7.326 NM_001814 37
    ||DPP1||CTSC||PLS||dipeptidyl
    transferase||cathepsin C||dipeptidyl-
    peptidase I||cathepsin J||Papillon-
    Lefevre syndrome||DIPEPTIDYL
    PEPTIDASE I||cathepsin C isoform b
    precursor||cathepsin C isoform a
    preproprotein||
    IGLV@ ||IGL73||immunoglobulin lambda 7.045 AK057174 38
    joining 3||
    OR2I6 ||||Similar to Olfactory receptor 2I2 6.874 XM_294092 39
    (LOC346170), mRNA||
    KCNJ2 ||HHBIRK1||HHIRK1||LQT7||KCNJ2|| 6.696 NM_000891 40
    potassium inwardly-rectifying
    channel J2||inward rectifier K+
    channel KIR2.1||cardiac inward
    rectifier potassium channel||inward
    rectifier potassium channel
    2||potassium inwardly-rectifying
    channel, subfamily J, member
    2||POTASSIUM CHANNEL,
    INWARDLY RECTIFYING, SUBFAMILY
    J, MEMBER 2||
    NTRK2 ||TRKB||NTRK2||TYROSINE KINASE 6.56 NM_006180 41
    RECEPTOR B||neurotrophic tyrosine
    kinase, receptor, type 2||
    TPSB2 ||||TPS1||tryptase, alpha|| 6.429 NM_003294 42
    CTSC ||HMS||CPPI||3.4.14.1||DPPI||PALS 6.299 NM_001814 43
    ||DPP1||CTSC||PLS||dipeptidyl
    transferase||cathepsin C||dipeptidyl-
    peptidase I||cathepsin J||Papillon-
    Lefevre syndrome||DIPEPTIDYL
    PEPTIDASE I||cathepsin C isoform b
    precursor||cathepsin C isoform a
    preproprotein||
    IFRG28 ||IFRG28||28 kD interferon 6.278 NM_022147 44
    responsive protein||
    HRH1 ||HRH1||H1-R||hisH1||histamine 6.191 NM_000861 45
    receptor H1||BPHS, MOUSE,
    HOMOLOG OF||histamine receptor,
    subclass H1||
    SCUBE2 ||SCUBE2||signal peptide, CUB 6.166 NM_020974 46
    domain, EGF-like 2||
    IGKC ||Km||HCAK1||IGKC||Immunoglobulin 6.073 BM993907 47
    kappa
    constant||IMMUNOGLOBULIN InV
    KAPPA-CHAIN
    DEFICIENCY||IMMUNOGLOBULIN
    KAPPA LIGHT
    CHAIN||immunoglobulin kappa
    constant region||kappa 1
    immunoglobulin light chain||Ig
    kappa chain C region||
    TPSB2 ||||TPS1||tryptase, alpha|| 6.028 NM_003294 48
    CHL1 ||L1CAM2||CHL1||CALL||neural cell 5.928 NM_006614 49
    adhesion molecule||cell adhesion
    molecule L1-like||CHL1, MOUSE,
    HOMOLOG OF||L1 cell adhesion
    molecule 2||cell adhesion molecule
    with homology to L1CAM
    precursor||cell adhesion molecule
    with homology to L1CAM (close
    homolog of L1)||
    IF ||3.4.21.45||IF||FACTOR I||FACTOR 5.687 NM_000204 50
    ‘EYE’||COMPLEMENT COMPONENT
    I||I factor (complement)||C3
    INACTIVATOR, DEFICIENCY OF||C3b
    INACTIVATOR COMPLEMENT
    COMPONENT 3 INACTIVATOR,
    DEFICIENCY OF||
    GLDC ||GLDC||HYGN1||GCSP||GCE||NKH|| 5.608 NM_000170 51
    1.4.4.2||GLYCINE CLEAVAGE
    SYSTEM P PROTEIN||glycine
    dehydrogenase (decarboxylating;
    glycine decarboxylase, glycine
    cleavage system protein P)||
    SEC6L1 ||||SEC6L1||SEC6-like 1 (S. cerevisiae) 5.608 NM_007277 52
    ||
    TPSB2 ||||TPS1||tryptase, alpha|| 5.573 NM_003294 53
    PKP2 ||PKP2||plakophilin 2|| 5.342 NM_004572 54
    PGDS ||PGDS||5.3.99.2||prostaglandin-D 5.265 NM_014485 55
    synthase||prostaglandin D2
    synthase,
    hematopoietic||hematopoietic
    prostaglandin D2 synthase||
    TFPI ||LACI||TFPI||EPI||EXTRINSIC 5.108 NM_006287 56
    PATHWAY INHIBITOR||tissue factor
    pathway inhibitor (lipoprotein-
    associated coagulation inhibitor)||
    ||Homo sapiens transcribed 5.094 BQ004901 57
    sequence with weak similarity to
    protein NP_060312.1
    BF ||GBG||BF||CFAB||PBF2||3.4.21.47|| 5.073 NM_001710 58
    C3 proaccelerator||glycine-rich
    beta-glycoprotein||B-factor,
    properdin||C3/C5 convertase||C3
    proactivator||PROPERDIN FACTOR
    B||FACTOR B,
    PROPERDIN||complement factor B
    preproprotein||
    TPK1 ||HTPK1||TPK1||THIAMINE 5.033 NM_022445 59
    KINASE||thiamine
    pyrophosphokinase||thiamin
    pyrophosphokinase 1||mouse
    thiamin pyrophosphokinase
    homolog||
    SLC16A1 ||SLC16A1||MCT1||monocarboxylate 4.941 NM_003051 60
    transporter 1||solute carrier family
    16, member 1||SOLUTE CARRIER
    FAMILY 16 (MONOCARBOXYLIC
    ACID TRANSPORTER), MEMBER
    1||solute carrier family 16
    (monocarboxylic acid transporters),
    member 1||
    PRRX1 ||PMX1||PRRX1||PRX1||homeobox 4.819 NM_006902 61
    protein PHOX1||PAIRED-RELATED
    HOMEOBOX GENE 1||paired related
    homeobox 1||paired mesoderm
    homeo box 1||paired mesoderm
    homeobox 1 isoform pmx-1a||paired
    mesoderm homeobox 1 isoform
    pmx-1b||
    CH25H ||CH25H||C25H||cholesterol 25- 4.732 NM_003956 62
    hydroxylase||
    LOC129607 ||LOC129607||hypothetical protein 4.61 XM_059368 63
    LOC129607||
    LOC340061 ||LOC340061||hypothetical protein 4.603 NM_198282 64
    LOC340061||
    IGKC ||Km||HCAK1||IGKC||Immunoglobulin 4.578 BM993907 65
    kappa
    constant||IMMUNOGLOBULIN InV
    KAPPA-CHAIN
    DEFICIENCY||IMMUNOGLOBULIN
    KAPPA LIGHT
    CHAIN||immunoglobulin kappa
    constant region||kappa 1
    immunoglobulin light chain||Ig
    kappa chain C region||
    4.542 CA314541 66
    FOXE1 ||TTF- 4.438 NM_004473 67
    2||FOXE1||TITF2||TTF2||FKHL15||forkhead
    (Drosophila)-like 15||thyroid
    transcription factor-2||Forkhead,
    drosophila, homolog-like
    15||forkhead box E1 (thyroid
    transcription factor 2)||
    SYNPO ||KIAA1029||synaptopodin||SYNPO|| 4.415 NM_007286 68
    ADRBK2 ||GRK3||BARK2||2.7.1.126||ADRBK2 4.385 NM_005160 69
    ||BETA-ADRENERGIC RECEPTOR
    KINASE 2||adrenergic, beta,
    receptor kinase 2||beta adrenergic
    receptor kinase 2||
    SLC28A3 ||SLC28A3||CNT3||CONCENTRATIVE 4.349 NM_022127 70
    NUCLEOSIDE TRANSPORTER
    3||solute carrier family 28 (sodium-
    coupled nucleoside transporter),
    member 3||
    CYP7B1 ||1.14.13.— 4.323 NM_004820 71
    ||CP7B||CYP7B1||oxysterol 7alpha-
    hydroxylase||OXYSTEROL 7-ALPHA-
    HYDROXYLASE 1||cytochrome P450,
    family 7, subfamily B, polypeptide
    1||cytochrome P450, subfamily VIIB
    (oxysterol 7 alpha-hydroxylase),
    polypeptide 1||
    APOL1 ||APOL1||APO-L||APOL- 4.259 NM_145343 72
    I||apolipoprotein L-I||apolipoprotein
    L, 1||apolipoprotein L1 isoform b
    precursor||apolipoprotein L1 isoform
    a precursor||
    MSLN ||CAK1||SMR||MSLN||mesothelin||MEGAKARYOCYTE- 4.254 NM_013404 73
    POTENTIATING
    FACTOR||SOLUBLE
    MPF/MESOTHELIN-RELATED
    PROTEIN||mesothelin isoform 2
    precursor||mesothelin isoform 1
    precursor||megakaryocyte
    potentiating factor
    precursor||ANTIGEN RECOGNIZED
    BY MONOCLONAL ANTIBODY K1||
    SFRP1 ||SFRP1||FRP- 4.239 NM_003012 74
    1||FrzA||SARP2||secreted
    apoptosis-related protein
    2||secreted frizzled-related protein
    1||
    GRK5 ||2.7.1.—||GRK5||GPRK5||G protein- 4.212 NM_005308 75
    coupled receptor kinase 5||
    MS4A2 ||FCERI||MS4A1||MS4A2||FCER1B 4.192 NM_000139 76
    ||Fc epsilon receptor I beta-
    chain||Fc IgE RECEPTOR, BETA
    CHAIN||MEMBRANE-SPANNING
    4 DOMAINS, SUBFAMILY A,
    MEMBER 2||immunoglobulin E
    receptor, high affinity, beta
    polypeptide||Fc FRAGMENT OF
    IgE, HIGH AFFINITY I,
    RECEPTOR FOR, BETA
    SUBUNIT||membrane-spanning
    4-domains, subfamily A, member
    2 (Fc fragment of IgE, high
    affinity I, receptor for; beta
    polypeptide)||
    PGBD5 ||PGBD5||piggyBac transposable 4.133 NM_024554 77
    element derived 5||
    GALNT4 ||||TUWD12|| 4.097 NM_003774 78
    HAS3 ||||HAS3||hyaluronan synthase 3|| 4.096 NM_005329 79
    CXCR4 CXCR4 4.092 AJ224869 80
    CDH3 ||CDHP||HJMD||PCAD||CDH3||placental 4.065 NM_001793 81
    cadherin||CADHERIN,
    PLACENTAL||cadherin 3, P-cadherin
    (placental)||calcium-dependent
    adhesion protein,
    placental||cadherin 3, type 1
    preproprotein||cadherin 3, type 1,
    P-cadherin (placental)||
    TPSB2 ||||TPS1||tryptase, alpha|| 4.033 NM_003294 82
    TPSB2 ||||TPS1||tryptase, alpha|| 3.98 NM_003294 83
    3.944 BM988338 84
    KITLG 3.939 AK055903 85
    FETUB ||FETUB||Gugu||16G2||IRL685||fetuin- 3.894 NM_014375 86
    like protein||fetuin B||
    SLC16A1 ||SLC16A1||MCT1||monocarboxylate 3.883 NM_003051 87
    transporter 1||solute carrier family
    16, member 1||SOLUTE CARRIER
    FAMILY 16 (MONOCARBOXYLIC
    ACID TRANSPORTER), MEMBER
    1||solute carrier family 16
    (monocarboxylic acid transporters),
    member 1||
    SGK ||2.7.1.— 3.879 NM_005627 88
    ||SGK||SGK1||SERUM/GLUCOCORTICOID-
    REGULATED
    KINASE||serum/glucocorticoid
    regulated kinase||serine/threonine
    protein kinase SGK||
    SIGLEC6 ||SIGLEC6||CD33L1||SIGLEC- 3.827 NM_001245 89
    6||OB-BINDING PROTEIN
    1||CD33 ANTIGEN-LIKE,
    MEMBRANE-BOUND||CD33
    antigen-like 1||CD33 ANTIGEN-
    LIKE, SOLUBLE||SIALIC ACID-
    BINDING IMMUNOGLOBULIN-
    LIKE LECTIN 6, SOLUBLE||sialic
    acid binding Ig-like lectin
    6||OBBP1 SIALIC ACID-
    BINDING IMMUNOGLOBULIN-
    LIKE LECTIN 6, MEMBRANE-
    BOUND||sialic acid binding Ig-
    like lectin 6 isoform b||sialic
    acid binding Ig-like lectin 6
    isoform a||sialic acid binding Ig-
    like lectin 6 isoform c||
    HTR2B ||5-HT(2B)||5- 3.818 NM_000867 90
    HT2B||HTR2B||SEROTONIN 5-HT-2B
    RECEPTOR||5-
    @HYDROXYTRYPTAMINE RECEPTOR
    2B||5-hydroxytryptamine
    (serotonin) receptor 2B||
    GPRC5B ||RAIG2||GPRC5B||RETINOIC ACID- 3.762 NM_016235 91
    INDUCIBLE GENE 2||G protein-
    coupled receptor, family C, group 5,
    member B||
    CTSC ||HMS||CPPI||3.4.14.1||DPPI||PALS 3.759 NM_001814 92
    ||DPP1||CTSC||PLS||dipeptidyl
    transferase||cathepsin C||dipeptidyl-
    peptidase I||cathepsin J||Papillon-
    Lefevre syndrome||DIPEPTIDYL
    PEPTIDASE I||cathepsin C isoform b
    precursor||cathepsin C isoform a
    preproprotein||
    3.721 AW978130 93
    SERPINE2 ||PN1||GDN||PNI||SERPINE2||PI7|| 3.69 NM_006216 94
    glial-derived nexin 1||glial-derived
    neurite promoting factor||protease
    inhibitor 7 (protease nexin
    I)||plasminogen activator inhibitor
    type 1, member 2||serine (or
    cysteine) proteinase inhibitor, clade
    E (nexin, plasminogen activator
    inhibitor type 1), member 2||
    CTSG ||MGC23078||CTSG||3.4.21.20||CG 3.626 NM_001911 95
    ||cathepsin G||cathepsin G
    preproprotein||
    LITAF ||LITAF||PIG7||TP53I7||FLJ38636|| 3.601 NM_004862 96
    CMT1C||SIMPLE||lipopolysaccharide-
    induced TNF factor||LPS-induced
    TNF-alpha
    factor||LIPOPOLYSACCHARIDE-
    INDUCED TUMOR NECROSIS
    FACTOR-ALPHA FACTOR||tumor
    protein p53 inducible protein
    7||small integral membrane protein
    of lysosome/late endosome||
    SLC2A3 ||GLUT3P1||SLC2A3P||SLC2A3||GLUCOSE 3.549 NM_006931 97
    TRANSPORTER 3
    PSEUDOGENE 1||GLUCOSE
    TRANSPORTER TYPE 3,
    BRAIN||solute carrier family 2
    (facilitated glucose transporter),
    member 3||GLUCOSE
    TRANSPORTER, FETAL SKELETAL
    MUSCLE SOLUTE CARRIER FAMILY
    2, MEMBER 3 PSEUDOGENE||
    IFI35 ||IFI35||IFP35||interferon-induced 3.545 NM_005533 98
    protein 35||INTERFERON INDUCIBLE
    PROTEIN, 35-KD||
    TPK1 ||HTPK1||TPK1||THIAMINE 3.491 NM_022445 99
    KINASE||thiamine
    pyrophosphokinase||thiamin
    pyrophosphokinase 1||mouse
    thiamin pyrophosphokinase
    homolog||
    MGC48998 ||MGC48998||hypothetical protein 3.481 NM_178550 100
    MGC48998||
    ITGA9 ||ALPHA- 3.453 NM_002207 101
    RLC||ITGA4L||ITGA9||INTEGRIN,
    ALPHA-9||integin, alpha 9||integrin,
    alpha 9||integrin, alpha 4-
    like||ALPHA RELATED TO THE
    DEVELOPMENT OF LUNG CANCER||
    IL17RB ||IL17RB||IL17RH1||IL17BR||INTERLEUKIN 3.446 NM_172234 102
    17B RECEPTOR||interleukin
    17 receptor B||INTERLEUKIN 17
    RECEPTOR HOMOLOG 1||
    PRG1 ||MGC9289||PPG||serglycin||PRG1|| 3.441 NM_002727 103
    hematopoetic proteoglycan core
    peptide||platelet proteoglycan
    protein core||proteoglycan 1,
    secretory granule||secretory granule
    proteoglycan core
    peptide||proteoglycan 1, secretory
    granule precursor||proteoglycan
    protein core for mast cell secretory
    granule||
    MRC1 ||MRC1||mannose receptor 3.394 NM_002438 104
    precursor||macrophage mannose
    receptor||mannose receptor, C type
    1||mannose receptor C type 1
    precursor||
    RARRES3 ||RIG1||TIG3||RARRES3||TAZAROTENE- 3.38 NM_004585 105
    INDUCED GENE 3||RETINOIC
    ACID RECEPTOR RESPONDER
    3||retinoic acid receptor responder
    (tazarotene induced) 3||
    DPYD ||1.3.1.2||DPYD||DIHYDROPYRIMIDINURIA 3.363 NM_000110 106
    ||dihydropyrimidine
    dehydrogenase||PYRIMIDINEMIA,
    FAMILIAL||5-@FLUOROURACIL
    TOXICITY||DPD
    DEFICIENCY||DIHYDROPYRIMIDINE
    DEHYDROGENASE
    DEFICIENCY||DHP THYMINE-
    URACILURIA, HEREDITARY||
    MFHAS1 ||MFHAS1||MASL1||MALIGNANT 3.356 NM_004225 107
    FIBROUS HISTIOCYTOMA-
    AMPLIFIED SEQUENCE 1||malignant
    fibrous histiocytoma amplified
    sequence 1||MFH-amplified
    sequences with leucine-rich tandem
    repeats 1||MALIGNANT FIBROUS
    HISTIOCYTOMA-AMPLIFIED
    SEQUENCES WITH LEUCINE-RICH
    TANDEM REPEATS 1||
    BCL2A1 ||HBPA1||BCL2A1||BCL2L5||GRS||BCL2- 3.355 NM_004049 108
    RELATED GENE BFL1||BCL2-
    related protein A1||hematopoietic
    BCL2-related protein A1||
    CFHL1 ||||HFL1||H factor (complement)- 3.347 NM_002113 109
    like 1||
    FGG ||FGG||fibrinogen, gamma 3.275 NM_021870 110
    polypeptide||FIBRINOGEN--GAMMA
    POLYPEPTIDE CHAIN||FIBRINOGEN,
    G GAMMA POLYPEPTIDE||fibrinogen,
    gamma chain isoform gamma-B
    precursor||fibrinogen, gamma chain
    isoform gamma-A precursor||
    IL27RA ||TCCR||IL27RA||CRL1||WSX1||zcytor1 3.27 NM_004843 111
    ||T-cell cytokine receptor||class I
    cytokine receptor||interleukin 27
    receptor, alpha||
    LOC130576 ||LOC130576||hypothetical protein 3.256 NM_177964 112
    LOC130576||
    LHFPL2 ||LHFPL2||KIAA0206||lipoma HMGIC 3.241 NM_005779 113
    fusion partner-like 2||
    RGS2 ||RGS2||BASIC HELIX-LOOP-HELIX 3.237 NM_002923 114
    PHOSPHOPROTEIN
    G0S8||REGULATOR OF G PROTEIN
    SIGNALING 2||regulator of G-
    protein signalling 2, 24 kDa||G0 to
    G1 switch regulatory 8, 24 kD||
    ENO1 ||4.2.1.11||ENO1L1||MPB1||MBP- 3.202 NM_001428 115
    1||tau-crystallin||ENO1||ENOLASE,
    ALPHA||non-neural enolase||2-
    phospho-D-glycerate hydrolyase
    ||ENOLASE,
    NONNEURONAL||phosphopyruvate
    hydratase||PPH CRYSTALLIN,
    TAU||enolase 1, (alpha)||MYC
    promoter-binding protein 1||
    MFHAS1 ||MFHAS1||MASL1||MALIGNANT 3.193 NM_004225 116
    FIBROUS HISTIOCYTOMA-
    AMPLIFIED SEQUENCE 1||malignant
    fibrous histiocytoma amplified
    sequence 1||MFH-amplified
    sequences with leucine-rich tandem
    repeats 1||MALIGNANT FIBROUS
    HISTIOCYTOMA-AMPLIFIED
    SEQUENCES WITH LEUCINE-RICH
    TANDEM REPEATS 1||
    TPSB2 ||||TPS1||tryptase, alpha|| 3.188 NM_003294 117
    SH3RF2 ||SH3RF2||SH3 domain containing 3.187 NM_152550 118
    ring finger 2||
    CISH ||CIS- 3.179 NM_013324 119
    1||SOCS||G18||CISH||cytokine
    inducible SH2-containing
    protein||suppressor of cytokine
    signaling||cytokine-inducible SH2-
    containing protein isoform
    1||cytokine-inducible SH2-
    containing protein isoform
    2||cytokine-inducible inhibitor of
    signaling type 1B||
    COL8A2 ||FECD||PPCD2||COL8A2||FLJ00201 3.148 NM_005202 120
    ||COLLAGEN, TYPE VIII, ALPHA-
    2||collagen VIII, alpha-2
    polypeptide||collagen, type VIII,
    alpha 2||
    LBH ||LBH||likely ortholog of mouse 3.147 NM_030915 121
    limb-bud and heart gene||
    SAMSN1 ||HACS1||SAMSN1||HEMATOPOIETIC 3.147 NM_022136 122
    ADAPTOR CONTAINING SH3 AND
    SAM DOMAINS 1||SAM domain, SH3
    domain and nuclear localisation
    signals, 1||SAM DOMAIN, SH3
    DOMAIN, AND NUCLEAR
    LOCALIZATION SIGNALS 1||
    SLC18A2 ||VAT2||SLC18A2||SVAT||VMAT2||SVMT 3.144 NM_003054 123
    ||VESICULAR AMINE
    TRANSPORTER 2||VESICULAR
    MONOAMINE TRANSPORTER
    2||SYNAPTIC VESICLE MONOAMINE
    TRANSPORTER, BRAIN||SYNAPTIC
    VESICLE AMINE TRANSPORTER,
    BRAIN||solute carrier family 18
    (vesicular monoamine), member
    2||SOLUTE CARRIER FAMILY 18
    (VESICULAR MONOAMINE
    TRANSPORTER), MEMBER 2||
    F13A1 ||FIBRINOLIGASE||TGase||F13A1||2.3.2.13 3.134 NM_000129 124
    ||FIBRINASE
    DEFICIENCY||FSF, A
    SUBUNIT||FACTOR XIII, A1
    SUBUNIT||FIBRIN STABILIZING
    FACTOR, A SUBUNIT||coagulation
    factor XIII, A1
    polypeptide||Coagulation factor XIII,
    A polypeptide||coagulation factor
    XIII A1 subunit
    precursor||TRANSGLUTAMINASE,
    PLASMA FACTOR XIII, A SUBUNIT,
    DEFICIENCY OF||
    3.131 AK095590 125
    ACSL5 ||ACSL5||FACL5||ACS5||ACYL-CoA 3.127 NM_016234 126
    SYNTHETASE 5||acyl-CoA
    synthetase long-chain family
    member 5||FATTY ACID CoA
    LIGASE, LONG-CHAIN 5||
    TNFSF13 ||TWE-PRIL||TALL2||TNFSF13||TNF- 3.116 NM_003808 127
    related death ligand-1||proliferation
    inducing ligand APRIl||tumor
    necrosis factor-related death ligand-
    1||tumor necrosis factor (ligand)
    superfamily, member 13||TNF- and
    APOL-related leukocyte expressed
    ligand 2||tumor necrosis factor
    ligand superfamily, member 13
    isoform delta||tumor necrosis factor
    ligand superfamily, member 13
    isoform gamma||tumor necrosis
    factor ligand superfamily, member
    13 isoform beta||tumor necrosis
    factor ligand superfamily, member
    13 isoform alpha precursor||
    STOM ||BND7||STOM||stomatin||EPB72||stomatin 3.104 NM_004099 128
    isoform a||stomatin isoform
    b||ERYTHROCYTE SURFACE
    PROTEIN BAND 7.2||ERYTHROCYTE
    BAND 7 INTEGRAL MEMBRANE
    PROTEIN||erythrocyte membrane
    protein band 7.2 (stomatin)||
    HDC ||HDC||4.1.1.22||histidine 3.073 NM_002112 129
    decarboxylase||
    KIAA1126 ||KIAA1126||KIAA1126 protein|| 3.071 AB032952 130
    PSMB9 ||3.4.25.1||RING12||LMP2||PSMB9|| 3.019 NM_002800 131
    macropain chain 7||proteasome-
    related gene 2||proteasome chain
    7||PROTEASOME SUBUNIT, BETA-
    TYPE, 9||proteasome subunit beta
    6i||proteasome catalytic subunit
    1i||low molecular mass protein
    2||proteasome subunit, beta type,
    9||multicatalytic endopeptidase
    complex chain 7||proteasome beta 9
    subunit isoform 1
    proprotein||proteasome beta 9
    subunit isoform 2
    proprotein||proteasome (prosome,
    macropain) subunit, beta type, 9
    (large multifunctional protease 2)||
    LRRC5 ||LRRC5||leucine rich repeat 3.014 NM_018103 132
    containing 5||
    GALNT5 ||GALNT5||UDP-N-acetyl-alpha-D- 2.991 NM_014568 133
    galactosamine:polypeptide N-
    acetylgalactosaminyltransferase 5
    (GalNAc-T5)||
    LOC340061 ||LOC340061||hypothetical protein 2.986 NM_198282 134
    LOC340061||
    SCIN ||scinderin||SCIN|| 2.985 NM_033128 135
    LR8 ||LR8||LR8 protein|| 2.941 NM_014020 136
    LOC126917 ||LOC126917||hypothetical protein 2.94 XM_375695 137
    LOC126917||
    HLF ||HLF||hepatic leukemia factor||HLF 2.932 NM_002126 138
    HLF/E2A FUSION GENE||
    TRIM22 ||GPSTAF50||RNF94||TRIM22||tripartite 2.931 NM_006074 139
    motif-containing 22||tripartite
    motif protein TRIM22||TRIPARTITE
    MOTIF-CONTAINING PROTEIN
    22||STIMULATED TRANS-ACTING
    FACTOR, 50-kD||stimulated trans-
    acting factor (50 kDa)||
    2.93 AW195474 140
    2.919 AA806368 141
    GCNT2 ||GCNT5||NAGCT1||BIGnT||ULG3||bA360O19.2 2.898 NM_001491 142
    ||CIGnT||bA421M1.1||GCNT2
    ||NACGT1||AIGnT||2.4.1.150||
    N-acetyllactosaminide beta-1,6-N-
    acetylglucosaminyltransferase||BETA-
    1,6-N-
    ACETYLGLUCOSAMINYLTRANSFERASE
    2||I beta-1,6-N-
    acetylglucosaminyltransferase||blood
    group Ii||Ii blood
    group||DEVELOPMENTAL I
    ANTIGEN||glucosaminyl (N-acetyl)
    transferase 5||glucosaminyl (N-
    acetyl) transferase 2 isoform
    A||glucosaminyl (N-acetyl)
    transferase 2 isoform
    B||glucosaminyl (N-acetyl)
    transferase 2 isoform
    C||glucosaminyl (N-acetyl)
    transferase 2, I-branching enzyme||
    LILRB2 ||||LILRB2||leukocyte 2.884 NM_005874 143
    immunoglobulin-like receptor,
    subfamily B (with TM and ITIM
    domains), member 2||
    IL15 ||IL- 2.879 NM_172174 144
    15||IL15||MGC9721||interleukin
    15||interleukin 15 isoform 2
    precursor||interleukin 15 isoform 1
    precursor||
    NFE2L3 ||NFE2L3||NRF3||NF-E2-related 2.867 NM_004289 145
    factor 3||NFE2-RELATED FACTOR
    3||NUCLEAR FACTOR ERYTHROID 2-
    LIKE 3||nuclear factor (erythroid-
    derived 2)-like 3||
    SH3RF2 ||SH3RF2||SH3 domain containing 2.826 NM_152550 146
    ring finger 2||
    KIAA1145 ||KIAA1145||KIAA1145 protein|| 2.82 NM_020698 147
    IL17RB ||IL17RB||IL17RH1||IL17BR||INTERLEUKIN 2.819 NM_172234 148
    17B RECEPTOR||interleukin
    17 receptor B||INTERLEUKIN 17
    RECEPTOR HOMOLOG 1||
    GPR110 ||GPR110||G protein-coupled 2.809 NM_153840 149
    receptor 110||
    TFPI ||LACI||TFPI||EPI||EXTRINSIC 2.808 NM_006287 150
    PATHWAY INHIBITOR||tissue factor
    pathway inhibitor (lipoprotein-
    associated coagulation inhibitor)||
    TNFSF13 ||TWE-PRIL||TALL2||TNFSF13||TNF- 2.79 NM_003808 151
    related death ligand-1||proliferation
    inducing ligand APRIl||tumor
    necrosis factor-related death ligand-
    1||tumor necrosis factor (ligand)
    superfamily, member 13||TNF- and
    APOL-related leukocyte expressed
    ligand 2||tumor necrosis factor
    ligand superfamily, member 13
    isoform delta||tumor necrosis factor
    ligand superfamily, member 13
    isoform gamma||tumor necrosis
    factor ligand superfamily, member
    13 isoform beta||tumor necrosis
    factor ligand superfamily, member
    13 isoform alpha precursor||
    LOH11CR2A ||BCSC-1||LOH11CR2A||loss of 2.772 NM_014622 152
    heterozygosity, 11, chromosomal
    region 2, gene A||
    TPPP ||p25||brain-specific protein p25 2.767 NM_007030 153
    alpha||glycogen synthase kinase 3
    (GSK3) inhibitor p24||
    Cep72 ||FLJ10565||hypothetical protein 2.758 NM_018140 154
    FLJ10565||
    CISH ||CIS- 2.74 NM_013324 155
    1||SOCS||G18||CISH||cytokine
    inducible SH2-containing
    protein||suppressor of cytokine
    signaling||cytokine-inducible SH2-
    containing protein isoform
    1||cytokine-inducible SH2-
    containing protein isoform
    2||cytokine-inducible inhibitor of
    signaling type 1B||
    MGC35033 ||MGC35033||hypothetical protein 2.739 NM_152319 156
    MGC35033||
    CNTN4 ||CNTN4||contactin 4||BIG2, RAT, 2.706 NM_175607 157
    HOMOLOG OF||
    NFE2L3 ||NFE2L3||NRF3||NF-E2-related 2.682 NM_004289 158
    factor 3||NFE2-RELATED FACTOR
    3||NUCLEAR FACTOR ERYTHROID 2-
    LIKE 3||nuclear factor (erythroid-
    derived 2)-like 3||
    CFH ||FHL1||CFH||HF1||HUS||complement 2.673 NM_000186 159
    factor H||H factor-1
    (complement)||H factor 1
    (complement)||HF FACTOR H-LIKE
    1||FACTOR H AND FACTOR H-LIKE
    1, COMBINED DEFICIENCY OF||
    PSMB8 ||MGC1491||RING10||LMP7||D6S216E 2.65 NM_004159 160
    ||PSMB8||3.4.25.1||large
    multifunctional protease-
    7||macropain subunit
    C13||proteasome subunit
    Y2||protease component
    C13||proteasome-related gene
    7||PROTEASOME SUBUNIT, BETA-
    TYPE, 8||proteasome subunit beta
    5i||proteasome catalytic subunit
    3i||multicatalytic endopeptidase
    complex subunit C13||proteasome
    subunit, beta type, 8||low molecular
    weight protein 7||proteasome beta 8
    subunit isoform E1
    proprotein||proteasome beta 8
    subunit isoform E2
    proprotein||proteasome (prosome,
    macropain) subunit, beta type, 8
    (large multifunctional protease 7)||
    LOXL4 ||LOXL4||LOXC||lysyl oxidase-like 2.647 NM_032211 161
    4||
    TRAF5 ||RNF84||MGC: 39780||TRAF5||TNF 2.613 NM_004619 162
    receptor-associated factor 5||
    CLN6 ||CLN6||CLN6 GENE||ceroid- 2.592 NM_017882 163
    lipofuscinosis, neuronal 6, late
    infantile, variant||
    HLF ||HLF||hepatic leukemia factor||HLF 2.587 NM_002126 164
    HLF/E2A FUSION GENE||
    SCUBE1 ||SCUBE1||signal peptide, CUB 2.577 NM_173050 165
    domain, EGF-like 1||
    CASP7 ||MCH3||CASP7||CMH-1||ICE- 2.573 NM_033339 166
    LAP3||Lice2
    alpha/beta/gamma||apoptotic
    protease MCH-3||ICE-like apoptotic
    protease 3||caspase 7 isoform
    beta||caspase 7 isoform alpha
    precursor||caspase 7, apoptosis-
    related cysteine protease||caspase 7
    isoform alpha, large
    subunit||caspase 7 isoform delta,
    large subunit||
    CLDN23 ||CLDN23||claudin 23|| 2.567 NM_194284 167
    SH3RF2 ||SH3RF2||SH3 domain containing 2.536 NM_152550 168
    ring finger 2||
    APOL3 ||APOL3||APOL- 2.535 NM_145641 169
    III||APOLIPOPROTEIN L-
    III||apolipoprotein L, 3||
    SEPX1 ||SEPX1||SELR||SELX||SELENOPROTEIN 2.519 NM_016332 170
    R||selenoprotein X, 1||
    FA2H ||FA2H||fatty acid 2-hydroxylase|| 2.516 NM_024306 171
    NEK6 ||NEK6||SID6-1512||NIMA-RELATED 2.498 NM_014397 172
    KINASE 6||putative serine-threonine
    protein kinase||NEVER IN MITOSIS
    GENE A-RELATED KINASE 6||NIMA
    (never in mitosis gene a)-related
    kinase 6||
    CLN6 ||CLN6||CLN6 GENE||ceroid- 2.493 NM_017882 173
    lipofuscinosis, neuronal 6, late
    infantile, variant||
    TM4SF8 ||TM4SF8||TSPAN-3 2.487 NM_005724 174
    1700055K04Rik||tetraspanin TM4-
    A||tetraspan TM4SF||tetraspanin
    3||tetraspan 3||transmembrane 4
    superfamily member
    8||transmembrane 4 superfamily,
    member 8||transmembrane 4
    superfamily member 8 isoform
    2||transmembrane 4 superfamily
    member 8 isoform 1||
    CLDN23 ||CLDN23||claudin 23|| 2.478 NM_194284 175
    EDAR ||ED5||ED3||EDAR||EDA- 2.473 NM_022336 176
    A1R||DL||EDA3||ED1R||ECTODYSPLASIN
    RECEPTOR||EDA-A1
    RECEPTOR||downless (mouse)
    homolog||ectodysplasin 1,
    anhidrotic
    receptor||ECTODYSPLASIN A1
    ISOFORM RECEPTOR||downless,
    mouse, homolog of||
    KLHL5 ||KLHL5||ketch-like 5 (Drosophila)|| 2.472 NM_199039 177
    VDR ||VDR||NR1I1||VITAMIN D 2.468 NM_000376 178
    RECEPTOR||1,25-
    @DIHYDROXYVITAMIN D3
    RECEPTOR||VITAMIN D HORMONE
    RECEPTOR||vitamin D (1,25-
    dihydroxyvitamin D3) receptor||
    SLC15A1 ||SLC15A1||HPECT1||peptide 2.463 NM_005073 179
    transporter HPEPT1||HYDROGEN
    ION/PEPTIDE COTRANSPORTER,
    INTESTINAL||solute carrier family
    15 (oligopeptide transporter),
    member 1||
    IFI30 ||IFI- 2.454 NM_006332 180
    30||IP30||IFI30||GILT||MGC32056||
    INTERFERON-GAMMA-INDUCIBLE
    PROTEIN 30||LYSOSOMAL THIOL
    REDUCTASE, GAMMA-INTERFERON-
    INDUCIBLE||interferon, gamma-
    inducible protein 30||gamma-
    interferon-inducible lysosomal thiol
    reductase||interferon, gamma-
    inducible protein 30 preproprotein||
    SLCO3A1 ||SLC21A11||OATP- 2.452 NM_013272 181
    D||SLCO3A1||OATP3A1||solute
    carrier organic anion transporter
    family, member 3A1||solute carrier
    family 21 (organic anion
    transporter), member 11||
    2.439 AK023647 182
    GALNT5 ||GALNT5||UDP-N-acetyl-alpha-D- 2.438 NM_014568 183
    galactosamine:polypeptide N-
    acetylgalactosaminyltransferase 5
    (GalNAc-T5)||
    LY75 ||GP200-MR6||DEC- 2.437 NM_002349 184
    205||LY75||DEC205||lymphocyte
    antigen 75||
    OR2A20P ||HSDJ0798C17||OR2A9P||olfactory 2.435 BC016940 185
    receptor, family 2, subfamily A,
    member 9 pseudogene||
    IGSF4 ||ST17||IGSF4||BL2||NECL2||SYNCAM 2.409 NM_014333 186
    ||TSLC1||nectin-like protein
    2||SYNAPTIC CELL ADHESION
    MOLECULE||immunoglobulin
    superfamily, member 4||tumor
    suppressor in lung cancer 1||
    NTRK3 ||NTRK3||TRKC||NEUROTROPHIN 3 2.382 NM_002530 187
    RECEPTOR||TYROSINE KINASE
    RECEPTOR C||neurotrophic tyrosine
    kinase, receptor, type 3||
    KIAA1337 ||KIAA1337||KIAA1337 protein|| 2.379 XM_052561 188
    GGH ||3.4.19.9||GGH||gamma-glutamyl 2.376 NM_003878 189
    hydrolase precursor||gamma-
    glutamyl hydrolase (conjugase,
    folylpolygammaglutamyl
    hydrolase)||
    P2RY1 ||P2RY1||ATP 2.363 NM_002563 190
    receptor||PURINOCEPTOR
    P2Y1||platelet ADP receptor||P2Y
    purinoceptor 1||purinergic receptor
    P2Y1||P2 purinoceptor subtype
    Y1||purinergic receptor P2Y, G-
    protein coupled, 1||PURINERGIC
    RECEPTOR P2Y, G PROTEIN-
    COUPLED, 1||
    APOL2 ||APOL2||APOL-II||apolipoprotein L- 2.347 NM_145637 191
    II||apolipoprotein L2||apolipoprotein
    L, 2||
    TAP1 ||RING4||ABC17||D6S114E||ABCB2 2.332 NM_000593 192
    ||TAP1||APT1||PEPTIDE
    TRANSPORTER
    PSF1||TRANSPORTER, ABC, MHC,
    1||ABC transporter, MHC 1||antigen
    peptide transporter 1||peptide
    supply factor 1||ABC TRANSPORTER,
    MHC, 1||ATP-BINDING CASSETTE,
    SUBFAMILY B, MEMBER
    2||TRANSPORTER ASSOCIATED
    WITH ANTIGEN PROCESSING
    1||ATP-binding cassette, sub-family
    B, member 2||ATP-binding cassette,
    sub-family B (MDR/TAP), member
    2||ATP-BINDING CASSETTE
    TRANSPORTER, MAJOR
    HISTOCOMPATIBILITY COMPLEX,
    1||transporter 1, ATP-binding
    cassette, sub-family B
    (MDR/TAP)||transporter, ATP-
    binding cassette, major
    histocompatibility complex, 1||
    SMILE ||FLJ90492||hypothetical protein 2.303 NM_181783 193
    FLJ90492||
    RRM2 ||1.17.4.1||RRM2||RIBONUCLEOTIDE 2.297 NM_001034 194
    REDUCTASE, R2
    SUBUNIT||RIBONUCLEOTIDE
    REDUCTASE, SMALL
    SUBUNIT||ribonucleotide reductase
    M2 polypeptide||RIBONUCLEOTIDE
    REDUCTASE, M2 SUBUNIT||
    PARP14 ||KIAA1268||KIAA1268 protein|| 2.276 BX648758 195
    PRICKLE2 ||PRICKLE2||prickle-like 2 2.272 NM_198859 196
    (Drosophila)||PRICKLE,
    DROSOPHILA, HOMOLOG OF, 2||
    NAV1 ||NAV1||neuron navigator 1|| 2.265 NM_020443 197
    RARB ||||RARB||retinoic acid receptor, 2.241 NM_000965 198
    beta||
    NDFIP2 ||NDFIP2||Nedd4 family interacting 2.233 XM_041162 199
    protein 2||
    LOC152485 ||LOC152485||hypothetical protein 2.231 NM_178835 200
    LOC152485||
    BAZ2A ||BAZ2A||KIAA0314||TIP5||TTF-I 2.228 NM_013449 201
    interacting peptide 5||bromodomain
    adjacent to zinc finger domain, 2A||
    ETV7 ||TELB||ETV7||ETS TRANSCRIPTION 2.212 NM_016135 202
    FACTOR TEL2||ets variant gene 7
    (TEL2 oncogene)||
    LTA4H ||3.3.2.6||LTA4H||leukotriene A4 2.205 NM_000895 203
    hydrolase||
    SLC16A1 ||SLC16A1||MCT1||monocarboxylate 2.194 NM_003051 204
    transporter 1||solute carrier family
    16, member 1||SOLUTE CARRIER
    FAMILY 16 (MONOCARBOXYLIC
    ACID TRANSPORTER), MEMBER
    1||solute carrier family 16
    (monocarboxylic acid transporters),
    member 1||
    ARMCX3 ||ALEX3||ALEX3 protein||ARM 2.192 NM_016607 205
    PROTEIN LOST IN EPITHELIAL
    CANCERS, X CHROMOSOME, 3||
    C10orf128 ||LOC170371||hypothetical protein 2.187 BC047724 206
    LOC170371||
    ARHGAP8 ||FLJ20185||ARHGAP8||PP610||BPGAP1 2.185 NM_017701 207
    ||BCH domain-containing
    Cdc42GAP-like protein||Rho GTPase
    activating protein 8||Rho GTPase
    activating protein 8 isoform 4||Rho
    GTPase activating protein 8 isoform
    1||Rho GTPase activating protein 8
    isoform 2||Rho GTPase activating
    protein 8 isoform 3||Rho GTPase
    activating protein 8 isoform 5||
    TMPRSS4 ||TMPRSS4||transmembrane 2.156 NM_019894 208
    protease, serine 4||
    CTSS ||CTSS||3.4.22.27||MGC3886||cathepsin 2.152 NM_004079 209
    S||cathepsin S preproprotein||
    LOC158402 2.144 AK095652 210
    TAPBP ||TAPBP||TPSN||TPN||NGS17||TAP- 2.131 NM_003190 211
    associated protein||TAP-binding
    protein||TAP binding protein
    (tapasin)||tapasin isoform 2
    precursor||tapasin isoform 1
    precursor||tapasin isoform 3
    precursor||
    CTEN ||CTEN||C-terminal tensin-like||C- 2.127 NM_032865 212
    TERMINAL TENSIN-LIKE PROTEIN||
    T3JAM ||T3JAM||TRAF3-INTERACTING JNK- 2.107 NM_025228 213
    ACTIVATING MODULATOR||TRAF3-
    interacting Jun N-terminal kinase
    (JNK)-activating modulator||
    CD44 ||CD44R||MDU2||INLU||MDU3||Pgp1 2.106 NM_000610 214
    ||MIC4||MC56||CD44||HERMES
    ANTIGEN||Lutheran inhibitor,
    dominant (monoclonal antibody
    A3D8)||CD44 antigen (homing
    function and Indian blood group
    system)||
    FLJ21103 ||FLJ21103||hypothetical protein 2.104 NM_024556 215
    FLJ21103||
    SLC16A2 ||SLC16A2||MCT8||XPCT||X-linked 2.09 NM_006517 216
    PEST-containing
    transporter||DXS128E
    MONOCARBOXYLATE TRANSPORTER
    8 DEFICIENCY||solute carrier family
    16, member 2||SOLUTE CARRIER
    FAMILY 16 (MONOCARBOXYLIC
    ACID TRANSPORTER), MEMBER
    2||solute carrier family 16
    (monocarboxylic acid transporters),
    member 2 (putative transporter)||
    GALNAC4S-6ST ||GalNAc4S- 2.083 NM_015892 217
    6ST||BRAG||KIAA0598||B-CELL
    RAG-ASSOCIATED GENE||N-
    ACETYLGALACTOSAMINE 4-SULFATE
    6-O-SULFOTRANSFERASE||B cell
    RAG associated protein||
    MAP3K14 ||FTDCR1B||MAP3K14||HSNIK||NF- 2.074 NM_003954 218
    KAPPA-B-INDUCING
    KINASE||serine/threonine protein-
    kinase||SERINE/THREONINE
    PROTEIN KINASE NIK||mitogen-
    activated protein kinase kinase
    kinase 14||
    ATP8B1 ||PFIC1||ATPIC||ATP8B1||BRIC||benign 2.064 NM_005603 219
    recurrent intrahepatic
    cholestasis||FAMILIAL
    INTRAHEPATIC CHOLESTASIS GENE
    1||ATPase, CLASS I, TYPE 8B,
    MEMBER 1||ATPase, Class I, type
    8B, member 1||progressive familial
    intrahepatic cholestasis 1, Byler
    disease||familial intrahepatic
    cholestasis 1, (progressive, Byler
    disease and benign recurrent)||
    RAB40B ||RAB40B||SEC4L||RAR||RAB40B, 2.063 NM_006822 220
    member RAS oncogene family||GTP-
    binding protein homologous to
    Saccharomyces cerevisiae SEC4||
    2.061 BQ717725 221
    NFKBIE ||NFKBIE||IKBE||INHIBITOR OF 2.06 NM_004556 222
    KAPPA LIGHT CHAIN GENE
    ENHANCER IN B CELLS,
    EPSILON||nuclear factor of kappa
    light polypeptide gene enhancer in
    B-cells inhibitor, epsilon||NUCLEAR
    FACTOR OF KAPPA LIGHT CHAIN
    GENE ENHANCER IN B CELLS
    INHIBITOR, EPSILON||
    2.058 AK026659 223
    ELOVL5 ||ELOVL5||ELOVL family member 5, 2.052 NM_021814 224
    elongation of long chain fatty acids
    (FEN1/Elo2, SUR4/Elo3-like,
    yeast)||
    LOC132430 2.047 XR_000195 225
    GPX4 ||snGPx||1.11.1.9||GPX4||sperm 2.045 NM_002085 226
    nucleus glutathione
    peroxidase||glutathione peroxidase
    4 (phospholipid hydroperoxidase)||
    CBX6 ||CBX6||chromobox homolog 6|| 2.041 NM_014292 227
    NCF1 ||p47- 2.031 NM_000265 228
    PHOX||NOXO2||NCF1||p47phox||Neutrophil
    cytosolic factor-1
    (47 kD)||neutrophil cytosolic factor 1
    (47 kDa, chronic granulomatous
    disease, autosomal 1)||neutrophil
    cytosolic factor 1 (47 kD, chronic
    granulomatous disease, autosomal
    1)||
    GLIPR1 ||RTVP1||GLIPR1||glioma 2.027 NM_006851 229
    pathogenesis-related protein||GLI
    pathogenesis-related 1
    (glioma)||related to testis-specific,
    vespid, and pathogenesis proteins
    1||
    CD44 ||CD44R||MDU2||INLU||MDU3||Pgp1 2.007 NM_000610 230
    ||MIC4||MC56||CD44||HERMES
    ANTIGEN||Lutheran inhibitor,
    dominant (monoclonal antibody
    A3D8)||CD44 antigen (homing
    function and Indian blood group
    system)||
    2.002 AK127315 231
    SLCO3A1 ||SLC21A11||OATP- 1.999 NM_013272 232
    D||SLCO3A1||OATP3A1||solute
    carrier organic anion transporter
    family, member 3A1||solute carrier
    family 21 (organic anion
    transporter), member 11||
    COL8A2 ||FECD||PPCD2||COL8A2||FLJ00201 1.992 NM_005202 233
    ||COLLAGEN, TYPE VIII, ALPHA-
    2||collagen VIII, alpha-2
    polypeptide||collagen, type VIII,
    alpha 2||
    KCTD12 ||KCTD12||potassium channel 1.985 NM_138444 234
    tetramerisation domain containing
    12||
    DLG5 ||PDLG||KIAA0583||DLG5||discs 1.969 NM_004747 235
    large homolog 5||placenta and
    prostate DLG||discs, large homolog
    5 (Drosophila)||DISCS LARGE,
    DROSOPHILA, HOMOLOG OF, 5||
    ABCC5 ||MOAT- 1.969 NM_005688 236
    C||ABCC5||MRP5||EST277145||ABC33
    ||SMRP||pABC11||MOATC||MULTI
    DRUG RESISTANCE-ASSOCIATED
    PROTEIN 5||canalicular multispecific
    organic anion transporter C||ATP-
    binding cassette, sub-family C,
    member 5||ATP-BINDING
    CASSETTE, SUBFAMILY C, MEMBER
    5||ATP-binding cassette, sub-family
    C (CFTR/MRP), member 5||
    PRSS12 ||leydin||BSSP3||MGC12722||BSSP- 1.965 NM_003619 237
    3||PRSS12||neurotrypsin
    precursor||brain-specific serine
    protease 3||protease, serine, 12
    (neurotrypsin, motopsin)||
    CLN5 ||NCL||CLN5||CLN5 GENE||ceroid- 1.96 NM_006493 238
    lipofuscinosis, neuronal 5||
    ZC3HDC1 ||ZC3HDC1||zinc finger CCCH type 1.947 NM_022750 239
    domain containing 1||
    EHD2 ||EHD2||EH-domain containing 1.94 NM_014601 240
    2||EH DOMAIN-CONTAINING 2||EH
    domain containing 2||
    RAD50 ||hRad50||RAD50||RAD50- 1.926 NM_005732 241
    2||RAD50 homolog (S. cerevisiae)
    ||RAD50 homolog isoform
    1||RAD50 homolog isoform
    2||RAD50, S. CEREVISIAE,
    HOMOLOG OF||
    GSDML ||||GSDML||gasdermin-like|| 1.92 NM_018530 242
    TLOC1 ||TLOC1||HTP1||Dtrp1 1.918 NM_003262 243
    protein||translocation protein
    1||TRANSLOCATION PROTEIN 1,
    DROSOPHILA, HOMOLOG
    OF||membrane protein SEC62,
    S. cerevisiae, homolog
    of||MEMBRANE PROTEIN SEC62, S. CEREVISIAE,
    HOMOLOG OF||
    EMR2 ||EMR2||EGF-LIKE MODULE- 1.914 NM_013447 244
    CONTAINING, MUCIN-LIKE
    HORMONE RECEPTOR 2||egf-like
    module containing, mucin-like,
    hormone receptor-like 2||egf-like
    module containing, mucin-like,
    hormone receptor-like sequence 2
    isoform d||egf-like module
    containing, mucin-like, hormone
    receptor-like sequence 2 isoform
    e||egf-like module containing,
    mucin-like, hormone receptor-like
    sequence 2 isoform f||egf-like
    module containing, mucin-like,
    hormone receptor-like sequence 2
    isoform g||egf-like module
    containing, mucin-like, hormone
    receptor-like sequence 2 isoform
    a||egf-like module containing,
    mucin-like, hormone receptor-like
    sequence 2 isoform b||egf-like
    module containing, mucin-like,
    hormone receptor-like sequence 2
    isoform c||
    NCF1 ||p47- 1.91 NM_000265 245
    PHOX||NOXO2||NCF1||p47phox||Neutrophil
    cytosolic factor-1
    (47 kD)||neutrophil cytosolic factor 1
    (47 kDa, chronic granulomatous
    disease, autosomal 1)||neutrophil
    cytosolic factor 1 (47 kD, chronic
    granulomatous disease, autosomal
    1)||
    ARHGEF6 ||alpha-PIX||alphaPIX||PIXA||Cool- 1.909 NM_004840 246
    2||MRX46||KIAA0006||ARHGEF6||COOL2
    ||PAK-interacting exchange
    factor, alpha||Rac/Cdc42 guanine
    exchange factor (GEF) 6||rho
    guanine nucleotide exchange factor
    6||Rac/Cdc42 guanine nucleotide
    exchange factor 6||Rac/Cdc42
    guanine nucleotide exchange factor
    (GEF) 6||
    ZSWIM5 ||ZSWIM5||zinc finger, SWIM 1.905 XM_046581 247
    domain containing 5||
    CHST6 ||||CHST6||carbohydrate (N- 1.897 NM_021615 248
    acetylglucosamine 6-O)
    sulfotransferase 6||
    EPLIN ||EPLIN||SREBP3||STEROL 1.897 NM_016357 249
    REGULATORY ELEMENT-BINDING
    PROTEIN 3||epithelial protein lost in
    neoplasm beta||
    IL27RA ||TCCR||IL27RA||CRL1||WSX1||zcytor1 1.897 NM_004843 250
    ||T-cell cytokine receptor||class I
    cytokine receptor||interleukin 27
    receptor, alpha||
    RGS19 ||RGSGAIP||RGS19||G alpha 1.891 NM_005873 251
    interacting protein||G PROTEIN,
    ALPHA-INTERACTING PROTEIN||G
    protein signalling regulator
    19||regulator of G-protein signalling
    19||REGULATOR OF G PROTEIN
    SIGNALING 19||guanine nucleotide
    binding protein alpha inhibiting
    activity polypeptide 3 interacting
    protein||
    ARRDC2 ||CLONE24945||PP2703||ARRDC2|| 1.887 NM_015683 252
    arrestin domain containing 2||
    HES2 ||||(Similar to Transcription factor 1.883 XM_375684 253
    HES-2 (Hairy and enhancer of split
    2) (LOC388592), mRNA||
    RIPK2 ||RIPK2||CARDIAK||RICK||CARD3|| 1.873 NM_003821 254
    RIP2||CARD-CONTAINING ICE-
    ASSOCIATED KINASE||RECEPTOR-
    INTERACTING PROTEIN 2||RIP-LIKE
    INTERACTING CLARP
    KINASE||RECEPTOR-INTERACTING
    SERINE/THREONINE KINASE
    2||receptor interacting protein
    2||receptor-interacting serine-
    threonine kinase 2||
    FGF11 ||FGF11||MGC45269||FHF3||fibroblast 1.868 NM_004112 255
    growth factor 11||fibroblast
    growth factor homologous factor 3||
    DRAP1 ||||Homo sapiens similar to 1.865 BC018095 256
    tankyrase, TRF1-interacting ankyrin-
    related ADP-ribose polymerase 2;
    tankyrase 2 (LOC376558), mRNA||
    SCIN ||scinderin||SCIN|| 1.861 NM_033128 257
    HSPA5BP1 ||HSPA5BP1||heat shock 70 kDa 1.861 NM_017870 258
    protein 5 (glucose-regulated protein,
    78 kDa) binding protein 1||
    ADAM8 ||MS2||CD156||ADAM8||HUMAN 1.858 NM_001109 259
    LEUKOCYTE DIFFERENTIATION
    ANTIGEN||a disintegrin and
    metalloproteinase domain 8||a
    disintegrin and metalloproteinase
    domain 8 precursor||
    NFATC2 ||NFATP||NFATC2||NFAT pre- 1.858 NM_173091 260
    existing subunit||NFAT
    TRANSCRIPTION COMPLEX,
    PREEXISTING COMPONENT||T cell
    transcription factor NFAT1||nuclear
    factor of activated T-cells,
    cytoplasmic 2||nuclear factor of
    activated T-cells, cytoplasmic,
    calcineurin-dependent 2||NUCLEAR
    FACTOR OF ACTIVATED T CELLS,
    PREEXISTING
    COMPONENT||preexisting nuclear
    factor of activated T-cells 2 isoform
    B||preexisting nuclear factor of
    activated T-cells 2 isoform
    C||NUCLEAR FACTOR OF ACTIVATED
    T CELLS, CYTOPLASMIC,
    CALCINEURIN-DEPENDENT 2||
    MGC14289 ||MGC14289||similar to RIKEN cDNA 1.858 NM_080660 261
    1200014N16 gene||
    GPR143 ||GPR143||OA1 GENE||ocular 1.854 NM_000273 262
    albinism-1, Nettleship-Falls type||G
    protein-coupled receptor
    143||ALBINISM, OCULAR, TYPE
    I||NETTLESHIP-FALLS TYPE OCULAR
    ALBINISM OCULAR ALBINISM 1
    GENE||
    1.845 AK056817 263
    FLJ10350 ||FLJ10350||hypothetical protein 1.845 NM_018067 264
    FLJ10350||
    HCP5 ||HCP5||D6S2650E||HLA complex 1.843 NM_006674 265
    P5||MHC class I region ORF||MAJOR
    HISTOCOMPATIBILITY COMPLEX,
    CLASS I, GENE P5-1||
    WARP ||WARP||von Willebrand factor A 1.831 NM_022834 266
    domain-related protein||
    MGC15397 ||MGC15397||similar to RIKEN cDNA 1.827 NM_080652 267
    5730578N08 gene||
    GLIS2 ||GLIS2||GLI-SIMILAR PROTEIN 1.82 NM_032575 268
    2||Kruppel-like zinc finger protein
    GLIS2||
    ARHGAP15 1.816 AI510829 269
    STK17B ||DRAK2||STK17B||SERINE/THREONINE 1.812 NM_004226 270
    PROTEIN KINASE 17B||death-
    associated protein kinase-related
    2||serine/threonine kinase 17b
    (apoptosis-inducing)||DAP KINASE-
    RELATED APOPTOSIS-INDUCING
    PROTEIN KINASE 2||
    CLNS1A ||||CLNS1A||chloride channel, 1.808 NM_001293 271
    nucleotide-sensitive, 1A||
    C9orf40 ||C9orf40||chromosome 9 open 1.8 NM_017998 272
    reading frame 40||
    FAM20C ||FAM20C||family with sequence 1.799 NM_020223 273
    similarity 20, member C||
    ADRBK2 ||GRK3||BARK2||2.7.1.126||ADRBK 1.791 NM_005160 274
    2||BETA-ADRENERGIC RECEPTOR
    KINASE 2||adrenergic, beta,
    receptor kinase 2||beta adrenergic
    receptor kinase 2||
    BBAP ||BBAP||rhysin 2|| 1.788 NM_138287 275
    EPB41L2 ||EPB41L2||4.1G||4.1- 1.765 NM_001431 276
    G||ERYTHROCYTE MEMBRANE
    PROTEIN 4.1-LIKE
    2||NONERYTHROID PROTEIN 4.1,
    GENERAL TYPE||erythrocyte
    membrane protein band 4.1-like 2||
    MGC7036 ||MGC7036||hypothetical protein 1.759 NM_145058 277
    MGC7036||
    1.759 BM999272 278
    TCF4 ||SEF2-1B||TCF4||E2- 1.756 NM_003199 279
    2||ITF2||transcription factor
    4||IMMUNOGLOBULIN
    TRANSCRIPTION FACTOR
    2||transcription factor 4 isoform
    b||Transcription factor-4
    (immunoglobulin transcription
    factor-2)||
    ARHGEF5 ||P60||ARHGEF5||TIM1||oncogene 1.753 NM_005435 280
    TIM||transforming immortalized
    mammary oncogene||guanine
    nucleotide regulatory protein
    TIM||Rho guanine nucleotide
    exchange factor 5||Rho guanine
    nucleotide exchange factor (GEF)
    5||
    SFXN1 ||SFXN1||sideroflexin 1|| 1.75 NM_022754 281
    KIAA1404 ||KIAA1404||KIAA1404 protein|| 1.746 NM_021035 282
    SMTN ||smoothelin||SMTN||smoothelin 1.745 NM_134269 283
    isoform a||smoothelin isoform
    b||smoothelin isoform c||
    TRAF4 ||CART1||MLN62||RNF83||TRAF4|| 1.739 NM_004295 284
    malignant 62||TNF receptor-
    associated factor 4||tumor necrosis
    receptor-associated factor 4A||TNF
    receptor-associated factor 4 isoform
    1||TNF receptor-associated factor 4
    isoform 2||CYSTEINE-RICH DOMAIN
    ASSOCIATED WITH RING AND TRAF
    DOMAINS||
    GCNT2 1.737 AK058074 285
    SPTBN1 ||||SPTBN1||spectrin, beta, non- 1.716 NM_003128 286
    erythrocytic 1||
    FOXQ1 ||FOXQ1||forkhead box Q1|| 1.709 NM_033260 287
    TNFRSF5 ||Bp50||TNFRSF5||MGC9013||CDW40 1.706 NM_001250 288
    ||CD40 antigen||CD40L
    receptor||B CELL-ASSOCIATED
    MOLECULE CD40||CD40 type II
    isoform||B cell surface antigen
    CD40||nerve growth factor receptor-
    related B-lymphocyte activation
    molecule||tumor necrosis factor
    receptor superfamily, member
    5||tumor necrosis factor receptor
    superfamily, member 5 isoform 2
    precursor||tumor necrosis factor
    receptor superfamily, member 5
    isoform 1 precursor||
    NCF4 ||p40phox||NCF4||p40-PHOX||NCF, 1.69 NM_013416 289
    40-KD||Neutrophil cytosolic factor-
    4||neutrophil cytosolic factor 4,
    40 kDa||neutrophil cytosolic factor 4
    (40 kD) isoform 1||neutrophil
    cytosolic factor 4 (40 kD) isoform 2||
    MGAT3 ||GNT- 1.688 NM_002409 290
    III||2.4.1.144||GNT3||MGAT3||BETA-
    1,4-@MANNOSYL-GLYCOPROTEIN
    BETA-1,4-N-
    ACETYLGLUCOSAMINYLTRANSFERASE
    ||UDP-N-
    ACETYLGLUCOSAMINE:BETA-D-
    MANNOSIDE BETA-1,4-N-
    ACETYLGLUCOSAMINYLTRANSFERASE
    ||mannosyl (beta-1,4-)-
    glycoprotein beta-1,4-N-
    acetylglucosaminyltransferase||
    DRAP1 ||||Homo sapiens similar to 1.687 BC018095 291
    tankyrase, TRF1-interacting ankyrin-
    related ADP-ribose polymerase 2;
    tankyrase 2 (LOC376558), mRNA||
    HLA-B ||HLA-B||HLA-B 1.686 NM_005514 292
    HISTOCOMPATIBILITY TYPE||major
    histocompatibility complex, class I,
    B||HLA class I histocompatibility
    antigen, B alpha chain||
    EPAS1 ||HIF2A||MOP2||HIF2- 1.684 NM_001430 293
    ALPHA||EPAS1||endothelial PAS
    domain protein 1||MEMBER OF PAS
    SUPERFAMILY 2||HYPDXIA-
    INDUCIBLE FACTOR 2, ALPHA
    SUBUNIT||
    LOC283578 ||LOC283578||hypothetical protein 1.684 XM_208746 294
    LOC283578||
    MAOA ||1.4.3.4||MAOA||MAOA BRUNNER 1.677 NM_000240 295
    SYNDROME||monoamine oxidase
    A||
    CDCP1 ||CDCP1||CUB domain-containing 1.663 NM_022842 296
    protein 1||
    TNIP2 ||TNIP2||TNFAIP3 interacting 1.66 NM_024309 297
    protein 2||
    RAB8B ||RAB8B||RAB8B, member RAS 1.653 NM_016530 298
    oncogene family||
    1.644 BM988141 299
    TLE4 ||ESG4||TLE4||E(spI)||BCE-1||B 1.636 NM_007005 300
    lymphocyte gene 1||transducin-like
    enhancer protein 4||enhancer of
    split groucho 4||transducin-like
    enhancer of split 4 (E(sp1) homolog,
    Drosophila)||
    ITGAE ||HUMINAE||ITGAE||CD103 1.635 NM_002208 301
    ANTIGEN||INTEGRIN, ALPHA-
    E||HUMAN MUCOSAL LYMPHOCYTE
    ANTIGEN 1, ALPHA
    SUBUNIT||integrin, alpha E (antigen
    CD103, human mucosal lymphocyte
    antigen 1; alpha polypeptide)||
    RAB33A ||RAB33A||MGC1488||RabS10||RAS- 1.63 NM_004794 302
    ASSOCIATED PROTEIN
    RAB33A||Ras-related protein Rab-
    33A||Small GTP-binding protein
    S10||RAB33A, member RAS
    oncogene family||
    CD97 ||CD97||TM7LN1||CD97 1.628 NM_078481 303
    antigen||leukocyte antigen
    CD97||seven-span transmembrane
    protein||CD97 antigen isoform 1
    precursor||CD97 antigen isoform 2
    precursor||
    SLCO3A1 ||SLC21A11||OATP- 1.623 NM_013272 304
    D||SLCO3A1||OATP3A1||solute
    carrier organic anion transporter
    family, member 3A1||solute carrier
    family 21 (organic anion
    transporter), member 11||
    TNIP2 ||TNIP2||TNFAIP3 interacting 1.618 NM_024309 305
    protein 2||
    GSTO1 ||GSTTLp28||GSTO1||glutathione-S- 1.615 NM_004832 306
    transferase like||glutathione-S-
    transferase omega 1||GLUTATHIONE
    S-TRANSFERASE, OMEGA-
    1||glutathione transferase
    omega||glutathione S-transferase
    omega 1||
    DTNBP1 ||SDY||DTNBP1||DYSBINDIN||DYSTROBREVIN- 1.597 NM_183040 307
    BINDING PROTEIN
    1||SANDY, MOUSE, HOMOLOG
    OF||dystrobrevin binding protein 1||
    ARHGAP26 ||GRAF||KIAA0621||GRAF 1.576 NM_015071 308
    GRAF/MLL FUSION GENE||GTPase
    regulator associated with focal
    adhesion kinase
    pp125(FAK)||GTPase regulator
    associated with the focal adhesion
    kinase pp125||
    KIAA1305 ||KIAA1305||KIAA1305 1.575 NM_025081 309
    protein||hypothetical protein
    FLJ11811||
    ETV7 ||TELB||ETV7||ETS TRANSCRIPTION 1.575 NM_016135 310
    FACTOR TEL2||ets variant gene 7
    (TEL2 oncogene)||
    DUOX1 ||DUOX1||THOX1||THYROID 1.567 NM_017434 311
    OXIDASE 1||dual oxidase 1||
    PIK3CD ||p110- 1.563 NM_005026 312
    DELTA||PIK3CD||p110D||phosphoinositide-
    3-kinase, catalytic, delta
    polypeptide||phosphatidylinositol 3-
    kinase, catalytic, delta
    polypeptide||PHOSPHATIDYLINOSITOL
    3-KINASE, CATALYTIC, 110-KD,
    DELTA||
    1.549 BG621254 313
    FAM46A ||C6orf37||chromosome 6 open 1.526 NM_017633 314
    reading frame 37||
    IRF6 ||PIT||LPS||IRF6||PPS||VWS||Popliteala 1.509 NM_006147 315
    pterygium
    syndrome||interferon regulatory
    factor 6||
    GSR ||1.6.4.2||GSR||glutathione 1.508 NM_000637 316
    reductase||GSR GLUTATHIONE
    REDUCTASE, HEMOLYTIC ANEMIA
    DUE TO DEFICIENCY OF, IN RED
    CELLS||
    1.506 AF143866 317
    ACOX1 ||MGC1198||1.3.3.6||ACOX1||PALMCOX 1.504 NM_004035 318
    ||SCOX||PSEUDONEONATAL
    ADRENOLEUKODYSTROPHY||PALMITOYL-
    CoA OXIDASE||ACYL-CoA
    OXIDASE, STRAIGHT-CHAIN||ACYL-
    CoA OXIDASE, PALMITOYL,
    PEROXISOMAL||PEROXISOMAL
    ACYL-CoA OXIDASE
    DEFICIENCY||acyl-Coenzyme A
    oxidase isoform a||acyl-Coenzyme A
    oxidase isoform b||acyl-Coenzyme A
    oxidase 1,
    palmitoyl||ADRENOLEUKODYSTROPHY,
    PSEUDONEONATAL ACYL-CoA
    OXIDASE 1, PALMITOYL||
    RAP1A ||RAP1A||SMGP21||KREV-1||RAP1A 1.486 NM_002884 319
    KREV1||RAS-related protein
    RAP1A||RAS-RELATED PROTEIN
    1A||RAP1A, member of RAS
    oncogene family||
    SIRT5 ||SIR2L5||SIRT5||sir2-like 5||sirtuin 1.479 NM_031244 320
    type 5||sirtuin 5 isoform 1||sirtuin 5
    isoform 2||SIR2, S. CEREVISIAE,
    HOMOLOG-LIKE 5||silent mating
    type information regulation 2,
    S. cerevisiae, homolog 5||sirtuin
    (silent mating type information
    regulation 2, S. cerevisiae, homolog)
    5||sirtuin (silent mating type
    information regulation 2 homolog) 5
    (S. cerevisiae)||sirtuin silent mating
    type information regulation 2
    homolog 5 (S. cerevisiae)||
    IL1RL1 ||ST2L||DER4||IL1RL1||ST2V||FIT- 1.479 NM_173459 321
    1||MGC32623||T1||ST2
    protein||interleukin 1 receptor-
    related protein||interleukin 1
    receptor-like 1||GROWTH
    STIMULATION-EXPRESSED GENE,
    MOUSE, HOMOLOG OF||homolog of
    mouse growth stimulation-expressed
    gene||interleukin 1 receptor-like 1
    isoform 1 precursor||interleukin 1
    receptor-like 1 isoform 2
    precursor||interleukin 1 receptor-
    like 1 isoform 3 precursor||
    GOT2 ||2.6.1.1||GOT2||ASPARTATE 1.477 NM_002080 322
    AMINOTRANSFERASE,
    MITOCHONDRIAL||aspartate
    aminotransferase 2
    precursor||GLUTAMATE
    OXALOACETATE TRANSAMINASE,
    MITOCHONDRIAL||glutamic-
    oxaloacetic transaminase 2,
    mitochondrial (aspartate
    aminotransferase 2)||
    1.456 BG257011 323
    PSME1 ||REGalpha||IFI5111||PA28- 1.455 NM_176783 324
    ALPHA||MGC8628||PSME1||PA28alpha
    ||proteasome activator subunit-
    1||PROTEASOME ACTIVATOR 28-
    ALPHA||interferon-gamma-inducible
    protein 5111||interferon-gamma IEF
    SSP 5111||MCP ACTIVATOR, 29-KD
    SUBUNIT||29-kD MCP activator
    subunit||11S regulator complex
    alpha subunit||interferon gamma
    up-regulated I-5111
    protein||proteasome activator
    subunit 1 isoform 2||proteasome
    activator subunit 1 isoform
    1||activator of multicatalytic
    protease subunit 1||proteasome
    (prosome, macropain) activator
    subunit 1 (PA28 alpha)||
    HA-1 ||HLA-HA1||HA-1||KIAA0223||minor 1.449 NM_012292 325
    histocompatibility antigen HA-1||
    IL9R ||IL9R||interleukin 9 1.44 NM_176786 326
    receptor||interleukin 9 receptor
    isoform 2||interleukin 9 receptor
    isoform 1 precursor||
    PRKAA1 ||PRKAA1||AMPK-ALPHA-1||AMPK 1.437 NM_006251 327
    alpha 1||AMP-ACTIVATED PROTEIN
    KINASE, CATALYTIC, ALPHA-
    1||Protein kinase, AMP-activated,
    catalytic, alpha-1||protein kinase,
    AMP-activated, alpha 1 catalytic
    subunit||
    SCARA3 ||CSR||MSRL1||SCARA3||CELLULAR 1.425 NM_016240 328
    STRESS RESPONSE||MACROPHAGE
    SCAVENGER RECEPTOR-LIKE
    1||scavenger receptor class A,
    member 3||
    MCM10 ||MCM10||MCM10 minichromosome 1.416 NM_182751 329
    maintenance deficient 10 (S. cerevisiae)
    ||
    C6orf83 ||C6orf83||chromosome 6 open 1.406 NM_145169 330
    reading frame 83||
    PSMB4 ||PROS26||PSMB4||HN3||3.4.25.1|| 1.385 NM_002796 331
    proteasome subunit
    HsN3||macropain beta
    chain||proteasome chain
    3||proteasome beta
    chain||proteasome beta 4
    subunit||PROTEASOME SUBUNIT,
    BETA-TYPE, 4||multicatalytic
    endopeptidase complex beta
    chain||proteasome subunit, beta
    type, 4||proteasome (prosome,
    macropain) subunit, beta type, 4||
    REPIN1 ||||REPIN1||replication initiator 1|| 1.378 NM_013400 332
    CYB561D1 ||FLJ39035||hypothetical protein 1.377 NM_182580 333
    FLJ39035||
    ARPC5L ||ARPC5L||actin related protein 2/3 1.367 NM_030978 334
    complex, subunit 5-like||
    DER1 ||PRO2577||MGC3067||FLJ13784||hypothetical 1.342 NM_018630 335
    protein MGC3067||
    KELCHL ||FLJ14360||hypothetical protein 1.317 NM_032775 336
    FLJ14360||
    SCML4 ||SCML4||sex comb on midleg-like 4 1.305 NM_198081 337
    (Drosophila)||
    KIAA0323 ||KIAA0323|| 1.26 AB002321 338
    C11orf31 ||SELH||selenoprotein H|| 1.25 NM_170746 339
    B2M ||beta-2-microglobulin||B2M||beta- 1.248 NM_004048 340
    2-microglobulin precursor||
    COX4I1 ||COXIV||COX4I1||CYTOCHROME c 1.201 NM_001861 341
    OXIDASE, SUBUNIT IV, ISOFORM
    1||cytochrome c oxidase subunit IV
    isoform 1||cytochrome c oxidase
    subunit IV isoform 1 precursor||
    RAC1 ||||RAC1||ras-related C3 botulinum 1.186 NM_198829 342
    toxin substrate 1 (rho family, small
    GTP binding protein Rac1)||
    COX4I1 ||COXIV||COX4I1||CYTOCHROME c 1.186 NM_001861 343
    OXIDASE, SUBUNIT IV, ISOFORM
    1||cytochrome c oxidase subunit IV
    isoform 1||cytochrome c oxidase
    subunit IV isoform 1 precursor||
    KIAA1228 ||KIAA1228||KIAA1228 protein|| 1.134 XM_036408 344
    SPRR3 ||esophagin||SPRR3||small proline- 0.863 NM_005416 345
    rich protein 3||
    SFRS15 ||SFRS15||splicing factor, 0.833 NM_020706 346
    arginine/serine-rich 15||
    ZCCHC2 ||ZCCHC2||zinc finger, CCHC 0.831 NM_017742 347
    domain containing 2||
    RGS11 ||RGS11||RS11||regulator of G- 0.815 NM_003834 348
    protein signalling 11||REGULATOR
    OF G PROTEIN SIGNALING
    11||regulator of G-protein signalling
    11 isoform 1||regulator of G-protein
    signalling 11 isoform 2||
    ZNF505 ||ZNF505||zinc finger protein 505|| 0.813 NM_031218 349
    SCAMP4 ||||SCAMP4||secretory carrier 0.793 NM_079834 350
    membrane protein 4||
    EIF2B4 ||EIF2B4||DKFZp586J0119||EIF2Bdelta 0.759 NM_172195 351
    ||EIF2B-DELTA||EUKARYOTIC
    TRANSLATION INITIATION FACTOR
    2B, DELTA||translation initiation
    factor eIF-2b delta
    subunit||eukaryotic translation
    initiation factor 2B, subunit 4 delta,
    67 kDa||eukaryotic translation
    initiation factor 2B, subunit 4 delta
    short isoform||eukaryotic translation
    initiation factor 2B, subunit 4 delta
    long isoform||
    SLC12A4 ||KCC1||SLC12A4||POTASSIUM- 0.758 NM_005072 352
    CHLORIDE COTRANSPORTER
    1||SOLUTE CARRIER FAMILY 12
    (POTASSIUM/CHLORIDE
    TRANSPORTER), MEMBER 4||solute
    carrier family 12 (potassium/chloride
    transporters), member 4||
    MGC33607 ||MGC33607||hypothetical protein 0.751 NM_152775 353
    MGC33607||
    ||Homo sapiens mRNA; cDNA 0.74 AL122093 354
    DKFZp434B2115 (from clone
    DKFZp434B2115)
    THEA ||THEA||STARD14||THEM1||KIAA0707 0.729 NM_147161 355
    BFIT1||THIOESTERASE,
    ADIPOSE-
    ASSOCIATED||thioesterase, adipose
    associated||BROWN FAT-INDUCIBLE
    THIOESTERASE||brown fat inducible
    thioesterase||START domain
    containing 14||thioesterase
    superfamily member
    1||thioesterase, adipose associated
    isoform BFIT1||thioesterase, adipose
    associated isoform BFIT2||
    SNX3 ||SNX3||SNX3A||SDP3||MGC17570|| 0.727 NM_152828 356
    sorting nexin 3||sorting nexin
    3A||sorting nexin 3 isoform
    a||sorting nexin 3 isoform b||sorting
    nexin 3 isoform c||
    HIPK2 ||HIPK2||PRO0593||EC 2.7.1.— 0.708 NM_014075 357
    ||Homeodomain-interacting protein
    kinase 2||homeodomain interacting
    protein kinase 2||
    PPP1CB ||PP- 0.708 NM_002709 358
    1B||PPP1CD||MGC3672||3.1.3.16||PPP1CB
    ||protein phosphatase 1-
    delta||protein phosphatase 1-
    beta||serine/threonine protein
    phosphatase PP1-beta catalytic
    subunit||protein phosphatase 1,
    ||catalytic subunit, beta
    isoform||protein phosphatase 1,
    catalytic subunit, delta
    isoform||protein phosphatase 1,
    catalytic subunit, beta isoform 1||
    SNX3 ||SNX3||SNX3A||SDP3||MGC17570|| 0.702 NM_152828 359
    sorting nexin 3||sorting nexin
    3A||sorting nexin 3 isoform
    a||sorting nexin 3 isoform b||sorting
    nexin 3 isoform c||
    EYA3 ||DKFZp686C132||EYA3||eyes 0.699 NM_001990 360
    absent 3 isoform a||eyes absent 3
    isoform b||eyes absent homolog 3
    (Drosophila)||EYES ABSENT,
    DROSOPHILA, HOMOLOG OF, 3||
    ESTs ESTs 0.699 AK025909 361
    Data not found 0.698 U55055 362
    DPCD ||DPCD||DKFZP566F084||DPCD 0.684 NM_015448 363
    protein||deleted in a mouse model
    of primary ciliary dyskinesia||
    TIGA1 ||TIGA1|| 0.675 NM_053000 364
    PABPC3 ||PABPL3||PABPC3||PABP3||POLYADENYLATE- 0.663 NM_030979 365
    BINDING PROTEIN
    3||poly(A)-binding protein-like
    3||POLYADENYLATE-BINDING
    PROTEIN-LIKE 3||testis-specific
    poly(A)-binding protein
    (PABP)||POLYADENYLATE-BINDING
    PROTEIN, CYTOPLASMIC, 3||testis-
    specific poly(A)-binding protein
    3||poly(A)-binding protein,
    cytoplasmic 3||poly(A) binding
    protein, cytoplasmic 3||
    C2orf4 ||||CGI-27||C21orf19-like protein|| 0.662 NM_015955 366
    SYT15 ||SYT15||SYNAPTOTAGMIN15 0.66 NM_031912 367
    ||synaptotagmin XV||
    PABPC1 ||PABPC1||PABPL1||PAB1||PABP1||POLYADENYLATE- 0.658 NM_002568 368
    BINDING PROTEIN
    1||POLY(A)-BINDING PROTEIN
    1||POLYADENYLATE-BINDING
    PROTEIN, CYTOPLASMIC, 1||poly(A)
    binding protein, cytoplasmic 1||
    RAB2 ||RAB2A||RAB2||RAS-ASSOCIATED 0.656 NM_002865 369
    PROTEIN RAB2||RAB2, member RAS
    oncogene family||
    MGC33993 ||MGC33993||hypothetical protein 0.653 NM_152737 370
    MGC33993||
    SC4MOL ||SC4MOL||DESP4||ERG25||sterol- 0.652 NM_006745 371
    C4-methyl oxidase-likel||STEROL C4-
    METHYLOXIDASE-LIKE||C-4 methyl
    sterol||
    KIAA1706 ||KIAA1706||KIAA1706 protein|| 0.65 NM_030636 372
    M-RIP ||RHOIP3||M-RIP||KIAA0864||Rho 0.649 NM_015134 373
    interacting protein 3||myosin
    phosphatase-Rho interacting
    protein||myosin phosphatase-Rho
    interacting protein isoform
    1||myosin phosphatase-Rho
    interacting protein isoform 2||
    C3orf4 ||C3orf4||chromosome 3 open 0.643 NM_019895 374
    reading frame 4||
    GAB2 ||KIAA0571||GAB2||Grb2- 0.638 NM_012296 375
    associated binder 2||GRB2-
    associated binding protein 2||GRB2-
    associated binding protein 2 isoform
    a||GRB2-associated binding protein
    2 isoform b||
    FLJ10156 ||FLJ10156||hypothetical protein 0.636 NM_019013 376
    FLJ10156||
    FBXO10 ||FBXO10||F-box protein Fbx10||F- 0.636 XM_291314 377
    box only protein 10||
    DNASE1 ||DNL1||3.1.21.1||DNASE1||deoxyribonuclease 0.633 NM_005223 378
    I||DNase I,
    LYSOSOMAL||
    ROD1 ||ROD1||fission yeast differentiation 0.633 NM_005156 379
    regulator||regulator of
    differentiation (in S. pombe)
    1||regulator of differentiation (in S. pombi)
    1||ROD1 regulator of
    differentiation 1 (S. pombe)||
    ATP6AP1 ||16A||CF2||ATP6AP1||VATPS1||ATP6S1 0.63 NM_001183 380
    ||Ac45||ORF||3.6.3.14||XAP3||ATP6IP1
    ||XAP-3||H-ATPase
    subunit||VACUOLAR ATPase
    SUBUNIT 1||V-ATPase S1 accessory
    protein||ATPase, H+
    TRANSPORTING, LYSOSOMAL,
    SUBUNIT 1||ATPase, H+
    transporting, lysosomal interacting
    protein 1||ATPase, H+ transporting,
    lysosomal accessory protein
    1||ATPase, H+ transporting,
    lysosomal accessory protein 1
    precursor||ATPase, H+ transporting,
    lysosomal (vacuolar proton pump),
    subunit 1||
    USP13 ||USP13||IsoT- 0.628 NM_003940 381
    3||ISOT3||ISOPEPTIDASE
    T3||UBIQUITIN-SPECIFIC PROTEASE
    13||ubiquitin specific protease 13
    (isopeptidase T-3)||
    CYB561 ||CYB561||CYTOCHROME 0.628 NM_001915 382
    b561||cytochrome b-561||
    PGM1 ||5.4.2.2||PGM1||phosphoglucomutase 0.619 NM_002633 383
    1||
    SAMD8 ||SAMD8||sterile alpha motif domain 0.618 NM_144660 384
    containing 8||
    IGSF11 ||IGSF11||BTIGSF||immunoglobulin 0.618 NM_152538 385
    superfamily, member 11||BRAIN-
    AND TESTIS-SPECIFIC
    IMMUNOGLOBULIN SUPERFAMILY
    PROTEIN||
    MAPK13 ||SAPK4||p38delta||PRKM13||p38- 0.617 NM_002754 386
    DELTA||MAPK13||mitogen-activated
    protein kinase 13||stress-activated
    protein kinase 4||PROTEIN KINASE,
    MITOGEN-ACTIVATED, 13||mitogen-
    activated protein kinase p38 delta||
    RABGAP1L ||KIAA0471||HHL||expressed in 0.615 NM_014857 387
    hematopoietic cells, heart, liver||
    QSCN6 ||||QSCN6||quiescin Q6|| 0.607 NM_002826 388
    MRPL37 ||MRPL37||mitochondrial ribosomal 0.599 NM_016491 389
    protein L37||
    RNF12 ||RNF12||RLIM||ring finger protein 0.597 NM_183353 390
    12||PUTATIVE RING ZINC FINGER
    PROTEIN NY-REN-43 ANTIGEN||
    DHCR24 ||SELADIN1||DHCR24||seladin- 0.591 NM_014762 391
    1||KIAA0018||24-
    dehydrocholesterol reductase||24-
    @DEHYDROCHOLESTEROL
    REDUCTASE||SELECTIVE AD
    INDICATOR 1||3 beta-hydroxysterol
    delta 24 reductase||
    AOX1 ||1.2.3.1||AOH1||AOX1||aldehyde 0.587 NM_001159 392
    oxidase 1||
    LOC340171 ||||Hypothetical LOC340171 0.587 BG928045 393
    (LOC340171), mRNA||
    LOC196264 ||LOC196264||hypothetical protein 0.585 NM_198275 394
    LOC196264||
    FLJ32421 ||FLJ32421||hypothetical protein 0.584 NM_144695 395
    FLJ32421||
    ZDHHC15 ||ZDHHC15||zinc finger, DHHC 0.584 NM_144969 396
    domain containing 15||
    ZC3HDC5 ||ZC3HDC5||zinc finger CCCH type 0.583 XM_036115 397
    domain containing 5||
    GAS7 ||GAS7||KIAA0394||MGC1348||growth 0.58 NM_201433 398
    arrest-specific 7||growth arrest-
    specific 7 isoform a||growth arrest-
    specific 7 isoform c||growth arrest-
    specific 7 isoform b||
    0.576 BF542107 399
    ELL2 ||ELL2||ELL-related RNA polymerase 0.575 NM_012081 400
    II, elongation factor||elongation
    factor, RNA polymerase II, 2||
    UNC13B ||hmunc13||UNC13B||Unc13h2||UNC13- 0.575 NM_006377 401
    LIKE||unc-13-like (C. elegans)
    ||UNC13 (C. elegans)-
    like||homolog of rat Munc13
    (diacylglycerol-binding)||unc-13
    homolog B (C. elegans)||
    SPRR3 ||esophagin||SPRR3||small proline- 0.569 NM_005416 402
    rich protein 3||
    CSTB ||STFB||CST6||CPI- 0.567 NM_000100 403
    B||PME||CSTB||liver thiol proteinase
    inhibitor||cystatin B (stefin B)||
    LOC199964 ||LOC199964||hypothetical protein 0.563 NM_182532 404
    LOC199964||
    C17orf39 ||MGC3048||hypothetical protein 0.562 NM_024052 405
    MGC3048||
    KRTHA2 ||KRTHA2||hHa2||Ha-2||keratin, 0.561 NM_002278 406
    hair, acidic, 2||keratin, hair, acidic,
    2||hard keratin, type I, 2||KERATIN,
    HARD, TYPE I, 2||type I hair keratin
    2||
    TYRO3 ||Brt||Dtk||RSE||Sky||BYK||Tif||TYRO3 0.56 NM_006293 407
    ||PROTEIN TYROSINE KINASE
    3||TYRO3 protein tyrosine
    kinase||tyrosine-protein kinase
    receptor TYRO3 precursor||Tyro3
    protein tyrosine kinase (sea-related
    receptor tyrosine kinase)||
    EPS8L1 ||EPS8L1||EPS8-like 1|| 0.558 NM_133180 408
    MAPK13 ||SAPK4||p38delta||PRKM13||p38- 0.554 NM_002754 409
    DELTA||MAPK13||mitogen-activated
    protein kinase 13||stress-activated
    protein kinase 4||PROTEIN KINASE,
    MITOGEN-ACTIVATED, 13||mitogen-
    activated protein kinase p38 delta||
    RNMT ||RNMT||RG7MT1||KIAA0398||RNA 0.553 NM_003799 410
    GUANINE-7-
    METHYLTRANSFERASE||RNA
    (guanine-7-) methyltransferase||
    NAP1L2 ||NAP1L2||MGC26243||brain specific 0.551 NM_021963 411
    gene BPX||nucleosome assembly
    protein 1-like 2||
    RGS11 ||RGS11||RS11||regulator of G- 0.551 NM_003834 412
    protein signalling 11||REGULATOR
    OF G PROTEIN SIGNALING
    11||regulator of G-protein signalling
    11 isoform 1||regulator of G-protein
    signalling 11 isoform 2||
    SRPRB RAB6B 0.55 AK055102 413
    HTCD37 ||||HTCD37||TcD37 homolog|| 0.545 NM_021222 414
    0.544 BX116062 415
    HIF1A ||HIF1-ALPHA||HIF1A||MOP1||HIF- 0.541 NM_001530 416
    1alpha||ARNT interacting
    protein||member of PAS superfamily
    1||hypoxia-inducible factor 1, alpha
    subunit isoform 2||hypoxia-inducible
    factor 1, alpha subunit isoform
    1||hypoxia-inducible factor 1, alpha
    subunit (basic helix-loop-helix
    transcription factor)||
    0.53 BG495068 417
    UBE2E2 ||||Hypothetical protein FLJ25157 0.529 NM_152653 418
    (FLJ25157), mRNA||
    MGC61716 0.524 NM_182501 419
    TPM4 ||||TPM4||tropomyosin 4|| 0.524 NM_003290 420
    PIM1 ||2.7.1.—||PIM1||pim-1 0.523 NM_002648 421
    oncogene||Oncogene
    PIM1||ONCOGENE PIM 1||
    FLJ32421 ||FLJ32421||hypothetical protein 0.523 NM_144695 422
    FLJ32421||
    PINK1 ||PINK1||PTEN-INDUCED PUTATIVE 0.513 NM_032409 423
    KINASE 1||PTEN induced putative
    kinase 1||
    TOM1 ||TOM1||target of myb1 0.513 NM_005488 424
    (chicken)||target of myb 1||target
    of myb1 (chicken)
    homolog||TARGET OF MYB1,
    CHICKEN, HOMOLOG OF||
    LOC142678 ||skeletrophin||LOC142678|| 0.511 NM_080875 425
    CAST ||CAST||MGC9402||calpastatin||heart- 0.51 NM_173060 426
    type calpastatin||calpain
    inhibitor||calpastatin isoform
    a||calpastatin isoform b||calpastatin
    isoform c||calpastatin isoform
    d||sperm BS-17 component||
    NPR3 ||NPR3||ANPRC||ATRIONATRIURETIC 0.509 NM_000908 427
    PEPTIDE RECEPTOR, TYPE
    C||ATRIAL NATRIURETIC PEPTIDE
    CLEARANCE RECEPTOR||natriuretic
    peptide receptor C/guanylate
    cyclase C (atrionatriuretic peptide
    receptor C)||
    MYEOV ||OCIM||MYEOV||myeloma 0.509 NM_138768 428
    overexpressed gene (in a subset of
    t(11; 14) positive multiple
    myelomas)||
    IMPA2 ||IMPA2||inositol(myo)-1(or 4)- 0.508 NM_014214 429
    monophosphatase 2||MYO-
    INOSITOL MONOPHOSPHATASE 2||
    FLJ13105 0.507 BF510602 430
    HIC ||HIC||I-mfa domain-containing 0.504 NM_199072 431
    protein||I-mfa domain-containing
    protein isoform p40||
    LOC55971 ||LOC55971||insulin receptor 0.504 NM_018842 432
    tyrosine kinase substrate||
    DSC2 ||desmocollin- 0.497 NM_004949 433
    3||DSC2||DGII/III||DG2/3||CDHF2||
    desmocollin 2||DSC3,
    FORMERLY||desmosomal
    glycoprotein II/III||DESMOCOLLIN
    3, FORMERLY||desmocollin 2 isoform
    Dsc2b preproprotein||desmocollin 2
    isoform Dsc2a preproprotein||
    CES4 ||||CES1||carboxylesterase 1 0.496 NM_016280 434
    (monocyte/macrophage serine
    esterase 1)||
    EPS8L1 ||EPS8L1||EPS8-like 1|| 0.495 NM_133180 435
    DKFZp434C0328 ||DKFZp434C0328||hypothetical 0.493 NM_017577 436
    protein DKFZp434C0328||
    LOC375035 ||LOC375035||hypothetical protein 0.493 NM_199344 437
    LOC375035||
    HIC ||HIC||I-mfa domain-containing 0.492 NM_199072 438
    protein||I-mfa domain-containing
    protein isoform p40||
    AK3 ||2.7.4.10||AK3||AK4||GTP:AMP 0.49 NM_013410 439
    phosphotransferase||adenylate
    kinase 3||adenylate kinase-3,
    mitochondrial||ADENYLATE KINASE,
    MITOCHONDRIAL||adenylate kinase
    isoenzyme 4, mitochondrial||
    M6PR ||CD- 0.486 NM_002355 440
    MPR||M6PR||MPR46||SMPR||Mr
    46,000 Man6PR||46-kDa mannose
    6-phosphate receptor||cation-
    dependent mannose-6-phosphate
    receptor precursor||MANNOSE 6-
    PHOSPHATE RECEPTOR, CATION-
    DEPENDENT||SMALL MANNOSE 6-
    PHOSPHATE RECEPTOR||mannose-
    6-phosphate receptor (cation
    dependent)||
    RPL18A ||||RPL18A||ribosomal protein 0.486 NM_000980 441
    L18a||
    EPS8L1 ||EPS8L1||EPS8-like 1|| 0.485 NM_133180 442
    AK3 ||2.7.4.10||AK3||AK4||GTP:AMP 0.481 NM_013410 443
    phosphotransferase||adenylate
    kinase 3||adenylate kinase-3,
    mitochondrial||ADENYLATE KINASE,
    MITOCHONDRIAL||adenylate kinase
    isoenzyme 4, mitochondrial||
    SOCS6 ||STAI4||SOCS4||CIS4||SOCS6||HSPC060 0.48 NM_004232 444
    ||SSI4||STATI4||STAT4||STAT
    induced STAT inhibitor-4||STAT-
    INDUCED STAT INHIBITOR
    4||cytokine-inducible SH2 protein
    4||suppressor of cytokine signaling
    6||suppressor of cytokine signaling
    4||
    C20orf161 ||C20orf161||chromosome 20 open 0.48 NM_033421 445
    reading frame 161||
    C10orf57 ||FLJ13263||hypothetical protein 0.479 NM_025125 446
    FLJ13263||
    USP13 ||USP13||IsoT- 0.479 NM_003940 447
    3||ISOT3||ISOPEPTIDASE
    T3||UBIQUITIN-SPECIFIC PROTEASE
    13||ubiquitin specific protease 13
    (isopeptidase T-3)||
    FN5 ||FN5||FN5 protein|| 0.478 NM_020179 448
    VARS2L ||DKFZP434L1435||KIAA1885 0.474 NM_020442 449
    protein||
    CDKN2B ||p14_INK4B||p15(INK4B)||CDKN2B 0.474 NM_078487 450
    ||TP15||MTS2||p15_INK4B||CDK4B
    inhibitor||p14_CDK inhibitor||CDK
    inhibitory protein||p15 CDK
    inhibitor||multiple tumor suppressor
    2||cyclin-dependent kinase 4
    inhibitor B||cyclin-dependent kinase
    inhibitor 2B isoform 1||cyclin-
    dependent kinase inhibitor 2B
    isoform 2||cyclin-dependent kinase
    inhibitor 2B (p15, inhibits
    CDK4)||cyclin-dependent kinases 4
    and 6 binding protein||
    PR1 ||PR1||voltage-dependent calcium 0.473 NM_183240 451
    channel gamma subunit-like
    protein||
    ENC1 ||PIG10||NRPB||ENC1||CCL28||ENC- 0.472 NM_003633 452
    1||TP53I10||NUCLEAR RESTRICTED
    PROTEIN/BRAIN||p53-INDUCED
    GENE 10||ECTODERMAL-NEURAL
    CORTEX 1||ectodermal-neural
    cortex (with BTB-like
    domain)||nuclear restricted protein,
    BTB domain-like (brain)||tumor
    protein p53 inducible protein 10||
    HIST2H2BE ||H2B.1||HIST2H2BE||H2B/q||H2BFQ 0.467 NM_003528 453
    ||GL105||histone 2, H2be||H2B
    histone family, member Q||HISTONE
    2B FAMILY, MEMBER Q||
    FLJ20674 ||||FLJ20674||hypothetical protein 0.463 NM_019086 454
    FLJ20674||
    CFLAR ||CASH||FLIP||Casper||CFLAR||I- 0.462 NM_003879 455
    FLICE||FLAME1||FLAME-
    1||CLARP||USURPIN||MRIT||CASPASE-
    EIGHT-RELATED PROTEIN||FLICE
    INHIBITORY PROTEIN||MACH-
    RELATED INDUCER OF
    TOXICITY||FADD-LIKE
    ANTIAPOPTOTIC MOLECULE
    1||CASP8 and FADD-like apoptosis
    regulator||CASP8- AND FADD-LIKE
    APOPTOSIS REGULATOR||FADD-like
    anti-apoptotic molecule; Inhibitor of
    FLICE; Caspase-related inducer of
    apoptosis; Caspase homolog;
    Caspase-like apoptosis regulatory
    protein||
    PTN ||HARP||HBNF||NEGF1||PTN||HBGF8 0.46 NM_002825 456
    ||heparin-binding growth-
    associated molecule||NEURITE
    OUTGROWTH-PROMOTING FACTOR,
    HEPARIN-BINDING||HEPARIN-
    BINDING GROWTH FACTOR
    8||heparin affin regulatory
    protein||pleiotrophin (heparin
    binding growth factor 8, neurite
    growth-promoting factor 1)||
    HOMER2 ||cupidin||HOMER2||HOMER- 0.46 NM_004839 457
    2||Vesl-2||ACPD||homer homolog 2
    (Drosophila)||HOMER 2B HOMER
    2A||homer homolog 3
    (Drosophila)||homer 2 isoform
    1||homer, neuronal immediate early
    gene, 2||
    MGLL ||lysophospholipase- 0.458 NM_007283 458
    like||MGLL||HU-K5||monoglyceride
    lipase||
    SLC16A9 ||SLC16A9||solute carrier family 16 0.458 NM_194298 459
    (monocarboxylic acid transporters),
    member 9||
    FLJ20674 ||||FLJ20674||hypothetical protein 0.456 NM_019086 460
    FLJ20674||
    MYOZ1 ||MYOZ1||myozenin 1||CALSARCIN 0.452 NM_021245 461
    2||
    0.445 BC033124 462
    RAP2A ||KREV||RAP2A||RbBP-30||RAS- 0.439 NM_021033 463
    RELATED PROTEIN 2A||RAP2A,
    member of RAS oncogene
    family||RAP2, member of RAS
    oncogene family (K-rev)||
    ELL2 ||ELL2||ELL-related RNA polymerase 0.431 NM_012081 464
    II, elongation factor||elongation
    factor, RNA polymerase II, 2||
    WASL ||MGC48327||N- 0.427 NM_003941 465
    WASP||WASL||Wiskott-Aldrich
    syndrome-like||Wiskott-Aldrich
    syndrome gene-like protein||neural
    Wiskott-Aldrich syndrome protein||
    HIC ||HIC||I-mfa domain-containing 0.426 NM_199072 466
    protein||I-mfa domain-containing
    protein isoform p40||
    MGC61716 Homo sapiens cDNA FLJ30912 fis, 0.426 NM_182501 467
    clone FEBRA2006346
    PTP4A1 ||PTP4A1||PRL1||PTPCAAX1||PTP(CAAX1) 0.424 NM_003463 468
    ||PRL-1||HH72||Protein
    tyrosine phosphatase
    IVA1||PHOPHATASE OF
    REGENERATING LIVER 1||PROTEIN-
    TYROSINE PHOSPHATASE, TYPE 4A,
    1||protein tyrosine phosphatase
    type IVA, member 1||
    GP1BB ||GP1BB||CD42c||GP Ib, BETA 0.423 NM_000407 469
    SUBUNIT||glycoprotein Ib beta
    polypeptide precursor||glycoprotein
    Ib (platelet), beta
    polypeptide||PLATELET
    GLYCOPROTEIN Ib, BETA
    POLYPEPTIDE||GLYCOPROTEIN Ib,
    PLATELET, BETA POLYPEPTIDE||
    PELI1 ||PELI1||pellino homolog 1 0.423 NM_020651 470
    (Drosophila)||
    PRKWNK1 ||PHA2C||PRKWNK1||PROTEIN 0.414 NM_018979 471
    KINASE, LYSINE-DEFICIENT 1||KDP
    PSEUDOHYPOALDOSTERONISM,
    TYPE IIC||protein kinase, lysine
    deficient 1||
    AMFR ||RNF45||GP78||AMFR||autocrine 0.408 NM_001144 472
    motility factor receptor||autocrine
    motility factor receptor isoform
    a||autocrine motility factor receptor
    isoform b||
    HPSE ||heparanase||HSE1||HPSE||HPSE1|| 0.403 NM_006665 473
    HPR1||heparanase-1||HPA||
    ST7L 0.402 AK128799 474
    CYP2C18 ||CYP2C18||1.14.14.1||P450IIC17|| 0.402 NM_000772 475
    P450-
    6B/29C||CYP2C17||CPCI||microsomal
    monooxygenase||flavoprotein-
    linked
    monooxygenase||CYTOCHROME
    P450, SUBFAMILY IIC, POLYPEPTIDE
    18||cytochrome P450, family 2,
    subfamily C, polypeptide
    18||cytochrome P450, subfamily IIC
    (mephenytoin 4-hydroxylase),
    polypeptide 17||cytochrome P450,
    subfamily IIC (mephenytoin 4-
    hydroxylase), polypeptide 18||
    ITCH ||ITCH||AIP4||NAPP1||ATROPHIN-1- 0.396 NM_031483 476
    INTERACTING PROTEIN 4||NFE2-
    ASSOCIATED POLYPEPTIDE
    1||ITCHY, MOUSE, HOMOLOG
    OF||itchy homolog E3 ubiquitin
    protein ligase (mouse)||
    PPP2R2C ||PPP2R2C||PR52||IMYPNO1||MGC33570 0.392 NM_020416 477
    ||PP2A, subunit B, PR55-
    gamma isoform||PP2A, subunit B,
    B55-gamma isoform||PP2A, subunit
    B, R2-gamma isoform||PP2A,
    subunit B, B-gamma
    isoform||protein phosphatase 2A1 B
    gamma subunit||phosphoprotein
    phosphatase 2A BR gamma
    regulatory chain||PROTEIN
    PHOSPHATASE 2A, REGULATORY
    SUBUNIT B, GAMMA
    ISOFORM||gamma isoform of
    regulatory subunit B55, protein
    phosphatase 2 isoform
    b||Serine/threonine protein
    phosphatase 2A, 55 KDA regulatory
    subunit B, gamma isoform||gamma
    isoform of regulatory subunit B55,
    protein phosphatase 2 isoform
    a||protein phosphatase 2 (formerly
    2A), regulatory subunit B (PR 52),
    gamma isoform||
    CCDC6 ||CCDC6||TPC||H4 0.392 NM_005436 478
    GENE||D10S170/H4 FUSION
    GENE||TRANSFORMING SEQUENCE,
    THYROID 1||coiled-coil domain
    containing 6||TST1 PTC1 CHIMERIC
    ONCOGENE||
    UACA ||UACA||uveal autoantigen with 0.391 NM_018003 479
    coiled-coil domains and ankyrin
    repeats||
    C20orf161 ||C20orf161||chromosome 20 open 0.389 NM_033421 480
    reading frame 161||
    0.385 AK024250 481
    DPCR1 ||DPCR1||PBLT||PANBRONCHIOLITIS, 0.384 NM_080870 482
    DIFFUSE||diffuse panbronchiolitis
    critical region 1||
    FLJ39501 ||FLJ39501||hypothetical protein 0.382 NM_173483 483
    FLJ39501||
    PFN2 ||D3S1319E||PFN2||profilin- 0.381 NM_053024 484
    2||PFL||profilin 2||profilin 2 isoform
    a||profilin 2 isoform b||
    C10orf57 ||FLJ13263||hypothetical protein 0.376 NM_025125 485
    FLJ13263||
    GSTA4 ||GSTA4||GSTA4- 0.376 NM_001512 486
    4||2.5.1.18||GTA4||GST class-
    alpha||glutathione S-
    aralkyltransferase A4||S-
    (hydroxyalkyl)glutathione lyase
    A4||GLUTATHIONE S-
    TRANSFERASE, ALPHA-
    4||glutathione transferase A4-
    4||glutathione S-transferase
    A4||glutathione S-aryltransferase
    A4||glutathione S-alkyltransferase
    A4||glutathione S-transferase, alpha
    4||
    DHRS1 ||DHRS1||dehydrogenase/reductase 0.359 NM_138452 487
    (SDR family) member 1||
    SLC7A5 ||SLC7A5||MPE16||D16S469E||CD98 0.358 NM_003486 488
    ||LAT1||4F2 light chain||Membrane
    protein E16||L-TYPE AMINO ACID
    TRANSPORTER 1||Solute carrier
    family 7, member 5||solute carrier
    family 7 (cationic amino acid
    transporter, y+ system), member
    5||
    LTB4DH ||LTB4DH||MGC34943||leukotriene 0.358 NM_012212 489
    B4 12-
    hydroxydehydrogenase||NADP-
    dependent leukotriene B4 12-
    hydroxydehydrogenase||
    SDR-O ||SDR-O||orphan short-chain 0.358 NM_148897 490
    dehydrogenase/reductase||
    SMPDL3A ||FLJ20177||yR36GH4.1||ASM3A||0610010C24Rik 0.357 NM_006714 491
    ||SMPDL3A||ASML3a||
    sphingomyelin phosphodiesterase,
    acid-like 3A||acid sphingomyelinase-
    like phosphodiesterase 3A||
    DEPDC6 ||DEPDC6||DEP domain containing 0.356 NM_022783 492
    6||
    CAP2 ||2810452G09Rik||CAP2||adenylyl 0.355 NM_006366 493
    cyclase-associated protein 2||CAP,
    adenylate cyclase-associated
    protein, 2 (yeast)||
    TUBB ||M40||TUBB||tubulin, beta 0.355 NM_001069 494
    polypeptide||
    SLC16A6 ||MCT6||SLC16A6||monocarboxylate 0.353 NM_004694 495
    transporter 6||solute carrier family
    16, member 6||SOLUTE CARRIER
    FAMILY 16 (MONOCARBOXYLIC
    ACID TRANSPORTER), MEMBER
    6||solute carrier family 16
    (monocarboxylic acid transporters),
    member 6||
    FLJ13910 ||FLJ13910||hypothetical protein 0.348 NM_022780 496
    FLJ13910||
    TMOD3 ||UTMOD||TMOD3||TROPOMODULIN, 0.346 NM_014547 497
    UBIQUITOUS||tropomodulin 3
    (ubiquitous)||
    PHGDH ||3PGDH||PHGDH||PDG||PGAD||SERA 0.343 NM_006623 498
    ||MGC3017||3-
    @PHOSPHOGYLCERATE
    DEHYDROGENASE||3-
    phosphoglycerate
    dehydrogenase||phosphoglycerate
    dehydrogenase||
    ARG2 ||ARG2||3.5.3.1||A-II||kidney 0.334 NM_001172 499
    arginase||nonhepatic arginase||L-
    arginine amidinohydrolase||L-
    arginine ureahydrolase||ARGINASE
    II||arginase, type II||arginase, type
    II precursor||
    NUCB2 ||NUCB2||NEFA||nucleobindin 2|| 0.331 NM_005013 500
    SPRR2B ||SPR-2B||SPRR2B||Small proline- 0.331 NM_006945 501
    rich protein 2B||
    NHLH2 ||NSCL2||NHLH2||HEN2||NEURONAL 0.329 NM_005599 502
    SCL-LIKE PROTEIN 2||nescient
    helix loop helix 2||
    AMACR ||AMACR||5.1.99.4||ALPHA- 0.328 NM_014324 503
    METHYLACYL-CoA
    RACEMASE||AMACR
    DEFICIENCY||AMACR ALPHA-
    METHYLACYL-CoA RACEMASE
    DEFICIENCY||alpha-methylacyl-CoA
    racemase isoform 1||alpha-
    methylacyl-CoA racemase isoform
    2||
    FLJ40432 ||FLJ40432||hypothetical protein 0.314 NM_152523 504
    FLJ40432||
    PRKWNK1 ||PHA2C||PRKWNK1||PROTEIN 0.302 NM_018979 505
    KINASE, LYSINE-DEFICIENT 1||KDP
    PSEUDOHYPOALDOSTERONISM,
    TYPE IIC||protein kinase, lysine
    deficient 1||
    TP53I3 ||TP53I3||PIG3||quinone 0.3 NM_004881 506
    oxidoreductase homolog||p53-
    induced gene 3 protein||tumor
    protein p53 inducible protein 3||
    CST6 ||CST6||cystatin 6||cystatin 0.3 NM_001323 507
    E/M||CYSTATIN M/E||cystatin M
    precursor||
    ZNF101 ||ZNF101||zinc finger protein 101|| 0.29 NM_033204 508
    FLJ25179 ||FLJ25179||hypothetical protein 0.286 NM_144670 509
    FLJ25179||
    RFK ||FLJ11149||riboflavin kinase|| 0.282 NM_018339 510
    AKR1C3 ||HA1753||1.1.1.188||DD3||hluPGFS 0.281 NM_003739 511
    ||HSD17B5||1.3.1.20||1.1.1.213||
    AKR1C3||KIAA0119||HAKRB||HAKRe
    ||trans-1,2-dihydrobenzene-1,2-
    diol dehydrogenase||chlordecone
    reductase homolog||dihydrodiol
    dehydrogenase 3||prostaglandin F
    synthase||ALDO-KETO REDUCTASE
    B||3-@ALPHA-HYDROXYSTEROID
    DEHYDROGENASE, TYPE
    II||hydroxysteroid (17-beta)
    dehydrogenase 5||type IIb 3-alpha
    hydroxysteroid
    dehydrogenase||aldo-keto reductase
    family 1, member C3 (3-alpha
    hydroxysteroid dehydrogenase, type
    II)||
    AKR1C1 ||1.1.1.213||2-ALPHA- 0.281 NM_001353 512
    HSD||1.3.1.20||20-ALPHA-
    HSD||MGC8954||H-
    37||HAKRC||MBAB||C9||DDH1||AKR1C1
    ||trans-1,2-dihydrobenzene-1,2-
    diol dehydrogenase||chlordecone
    reductase homolog||aldo-keto
    reductase C||20 alpha-
    hydroxysteroid
    dehydrogenase||hepatic dihydrodiol
    dehydrogenase||dihydrodiol
    dehydrogenase isoform DD1||type II
    3-alpha-hydroxysteroid
    dehydrogenase||DIHYDRODIOL
    DEHYDROGENASE, TYPE I||ALDO-
    KETO REDUCTASE FAMILY 1,
    MEMBER 1||aldo-keto reductase
    family 1, member C1 (dihydrodiol
    dehydrogenase 1; 20-alpha (3-
    alpha)-hydroxysteroid
    dehydrogenase)||
    NQO1 ||NMORI||diaphorase- 0.28 NM_000903 513
    4||NQO1||QR1||DTD||DHQU||NMOR1
    ||DIA4||DIAPHORASE 4||NAD(P)H
    dehydrogenase, quinone
    1||diaphorase (NADH/NADPH)
    (cytochrome b-5
    reductase)||NAD(P)H:menadione
    oxidoreductase 1, dioxin-inducible
    1||NAD(P)H menadione
    oxidoreductase 1, dioxin-inducible||
    LOC283824 ||LOC283824||hypothetical protein 0.279 BX647541 514
    LOC283824||
    C6orf56 ||C6orf56||KIAA0680||KIAA0680 0.268 NM_014721 515
    gene product||chromosome 6 open
    reading frame 56||
    FAM43A ||FLJ90022||hypothetical protein 0.263 NM_153690 516
    FLJ90022||
    SH3GL3 ||EEN- 0.26 NM_003027 517
    B2||SH3D2C||SH3GL3||SH3p13||HsT19371
    ||CNSA3||ENDOPHILIN
    A3||SH3-domain GRB2-like 3||SH3
    DOMAIN, GRB2-LIKE, 3||
    AKR1C1 ||1.1.1.213||2-ALPHA- 0.257 NM_001353 518
    HSD||1.3.1.20||20-ALPHA-
    HSD||MGC8954||H-
    37||HAKRC||MBAB||C9||DDH1||AKR1C1
    ||trans-1,2-dihydrobenzene-1,2-
    diol dehydrogenase||chlordecone
    reductase homolog||aldo-keto
    reductase C||20 alpha-
    hydroxysteroid
    dehydrogenase||hepatic dihydrodiol
    dehydrogenase||dihydrodiol
    dehydrogenase isoform DD1||type II
    3-alpha-hydroxysteroid
    dehydrogenase||DIHYDRODIOL
    DEHYDROGENASE, TYPE I||ALDO-
    KETO REDUCTASE FAMILY 1,
    MEMBER 1||aldo-keto reductase
    family 1, member C1 (dihydrodiol
    dehydrogenase 1; 20-alpha (3-
    alpha)-hydroxysteroid
    dehydrogenase)||
    AKR1C2 ||BABP||DD2||1.3.1.20||HBAB||1.1.1.213 0.256 NM_001354 519
    ||HAKRD||MCDR2||AKR1C2||DDH2
    ||AKR1C-pseudo||pseudo-
    chlordecone reductase||trans-1,2-
    dihydrobenzene-1,2-diol
    dehydrogenase||chlordecone
    reductase homolog||ALDO-KETO
    REDUCTASE D||3-@ALPHA-
    HYDROXYSTEROID
    DEHYDROGENASE, TYPE III||type
    III 3-alpha-hydroxysteroid
    dehydrogenase||DIHYDRODIOL
    DEHYDROGENASE, TYPE II||type II
    dihydrodiol dehydrogenase||aldo-
    keto reductase family 1, member C2
    (dihydrodiol dehydrogenase 2; bile
    acid binding protein; 3-alpha
    hydroxysteroid dehydrogenase, type
    III)||
    C20orf161 ||C20orf161||chromosome 20 open 0.255 NM_033421 520
    reading frame 161||
    ACPP ||3.1.3.2||ACPP||PAP||acid 0.254 NM_001099 521
    phosphatase,
    prostate||PHOSPHATASE,
    PROSTATE-SPECIFIC
    ACID||prostatic acid phosphatase
    precursor||
    AKR1C2 ||BABP||DD2||1.3.1.20||HBAB||1.1.1.213 0.251 NM_001354 522
    ||HAKRD||MCDR2||AKR1C2||DDH2
    ||AKR1C-pseudo||pseudo-
    chlordecone reductase||trans-1,2-
    dihydrobenzene-1,2-diol
    dehydrogenase||chlordecone
    reductase homolog||ALDO-KETO
    REDUCTASE D||3-@ALPHA-
    HYDROXYSTEROID
    DEHYDROGENASE, TYPE III||type
    III 3-alpha-hydroxysteroid
    dehydrogenase||DIHYDRODIOL
    DEHYDROGENASE, TYPE II||type II
    dihydrodiol dehydrogenase||aldo-
    keto reductase family 1, member C2
    (dihydrodiol dehydrogenase 2; bile
    acid binding protein; 3-alpha
    hydroxysteroid dehydrogenase, type
    III)||
    ASAH3 ||ASAH3||N-acylsphingosine 0.251 NM_133492 523
    amidohydrolase (alkaline
    ceramidase) 3||
    C9orf58 ||C9orf58||chromosome 9 open 0.25 NM_031426 524
    reading frame 58||
    NQO1 ||NMORI||diaphorase- 0.248 NM_000903 525
    4||NQO1||QR1||DTD||DHQU||NMOR1
    ||DIA4||DIAPHORASE 4||NAD(P)H
    dehydrogenase, quinone
    1||diaphorase (NADH/NADPH)
    (cytochrome b-5
    reductase)||NAD(P)H:menadione
    oxidoreductase 1, dioxin-inducible
    1||NAD(P)H menadione
    oxidoreductase 1, dioxin-inducible||
    S100A12 ||MRP6||CAAF1||ENRAGE||CGRP||S100A12 0.247 NM_005621 526
    ||CALGRANULIN-RELATED
    PROTEIN||S100 calcium-binding
    protein A12||CALCIUM-BINDING
    PROTEIN IN AMNIOTIC
    FLUID||EXTRACELLULAR NEWLY
    IDENTIFIED RAGE-BINDING
    PROTEIN||S100 calcium binding
    protein A12 (calgranulin C)||
    0.247 BG218400 527
    PCSK5 ||PC6A||3.4.21.— 0.246 NM_006200 528
    ||PCSK5||SPC6||protease
    PC6||proprotein convertase
    PC5||subtilisin/kexin-like protease
    PC5||prohormone convertase
    5||PROPROTEIN CONVERTASE,
    SUBTILISIN/KEXIN-TYPE,
    5||Proprotein convertase
    subtilisin/kexin type 5||proprotein
    convertase subtilisin/kexin type 5
    preproprotein||
    EML1 ||ELP79||EMAPL||EML1||HuEMAP||ECHINODERM 0.244 NM_004434 529
    MICROTUBULE-
    ASSOCIATED PROTEIN-LIKE
    1||echinoderm microtubule
    associated protein like 1||
    NQO1 ||NMORI||diaphorase- 0.241 NM_000903 530
    4||NQO1||QR1||DTD||DHQU||NMOR1
    ||DIA4||DIAPHORASE 4||NAD(P)H
    dehydrogenase, quinone
    1||diaphorase (NADH/NADPH)
    (cytochrome b-5
    reductase)||NAD(P)H:menadione
    oxidoreductase 1, dioxin-inducible
    1||NAD(P)H menadione
    oxidoreductase 1, dioxin-inducible||
    DPCR1 ||DPCR1||PBLT||PANBRONCHIOLITIS, 0.238 NM_080870 531
    DIFFUSE||diffuse panbronchiolitis
    critical region 1||
    C6orf33 ||MPRB||LMPB1||C6orf33||MEMBRANE 0.232 NM_133367 532
    PROGESTIN RECEPTOR,
    BETA||LYSOSOMAL MEMBRANE
    PROTEIN, BRAIN-EXPRESSED,
    1||chromosome 6 open reading
    frame 33||
    BNIP3 ||BNIP3||BCL2/adenovirus E1B 0.23 NM_004052 533
    19 kD-interacting protein
    3||BCL2/adenovirus E1B 19 kDa
    interacting protein
    3||BCL2/ADENOVIRUS E1B 19-KD
    PROTEIN-INTERACTING PROTEIN
    3||BCL2/adenovirus E1B 19 kD
    interacting protein
    3||BCL2/adenovirus E1B 19-kDa
    protein-interacting protein 3||
    C6orf33 ||MPRB||LMPB1||C6orf33||MEMBRANE 0.228 NM_133367 534
    PROGESTIN RECEPTOR,
    BETA||LYSOSOMAL MEMBRANE
    PROTEIN, BRAIN-EXPRESSED,
    1||chromosome 6 open reading
    frame 33||
    FLJ40432 ||FLJ40432||hypothetical protein 0.227 NM_152523 535
    FLJ40432||
    na 0.218 XM_379456 536
    RDH12 ||RDH12||retinol dehydrogenase 12 0.216 NM_152443 537
    (all-trans and 9-cis)||
    C9orf58 ||C9orf58||chromosome 9 open 0.215 NM_031426 538
    reading frame 58||
    MGC11324 ||MGC11324||hypothetical protein 0.212 NM_032717 539
    MGC11324||
    PCSK5 ||PC6A||3.4.21.— 0.212 NM_006200 540
    ||PCSK5||SPC6||protease
    PC6||proprotein convertase
    PC5||subtilisin/kexin-like protease
    PC5||prohormone convertase
    5||PROPROTEIN CONVERTASE,
    SUBTILISIN/KEXIN-TYPE,
    5||proprotein convertase
    subtilisin/kexin type 5||proprotein
    convertase subtilisin/kexin type 5
    preproprotein||
    HSPA2 ||HSPA1A||heat shock-induced 0.211 U56725 541
    protein||HEAT-SHOCK 70-KD
    PROTEIN 1A||dnaK-type molecular
    chaperone HSP70-1||HEAT-SHOCK
    PROTEIN, 70-KD, 1||heat shock
    70 kDa protein 1A||heat shock 70 kD
    protein 1A||
    ZNF426 ||ZNF426||zinc finger protein 426|| 0.209 NM_024106 542
    BPGM 0.205 BG030612 543
    ME1 ||MES||1.1.1.40||HUMNDME||ME1|| 0.204 NM_002395 544
    pyruvic-malic carboxylase||MALIC
    ENZYME, SOLUBLE||Malic enzyme,
    cytoplasmic||NADP-dependent malic
    enzyme||cytosolic malic enzyme
    1||MALATE DEHYDROGENASE,
    NADP(+)-DEPENDENT,
    SOLUBLE||malic enzyme 1,
    soluble||MALIC ENZYME, NADP(+)-
    DEPENDENT, CYTOSOLIC||malic
    enzyme 1, NADP(+)-dependent,
    cytosolic||
    LOC284233 0.202 BC037172 545
    FNDC4 ||FNDC4||fibronectin type III 0.2 NM_022823 546
    domain containing 4||
    ACPP ||3.1.3.2||ACPP||PAP||acid 0.199 NM_001099 547
    phosphatase,
    prostate||PHOSPHATASE,
    PROSTATE-SPECIFIC
    ACID||prostatic acid phosphatase
    precursor||
    LOC56901 ||LOC56901||NADH:ubiquinone 0.194 NM_020142 548
    oxidoreductase MLRQ subunit
    homolog||
    FLJ21511 ||FLJ21511||hypothetical protein 0.191 NM_025087 549
    FLJ21511||
    PCSK5 ||PC6A||3.4.21.— 0.19 NM_006200 550
    ||PCSK5||SPC6||protease
    PC6||proprotein convertase
    PC5||subtilisin/kexin-like protease
    PC5||prohormone convertase
    5||PROPROTEIN CONVERTASE,
    SUBTILISIN/KEXIN-TYPE,
    5||proprotein convertase
    subtilisin/kexin type 5||proprotein
    convertase subtilisin/kexin type 5
    preproprotein||
    ME1 ||MES||1.1.1.40||HUMNDME||ME1|| 0.186 NM_002395 551
    pyruvic-malic carboxylase||MALIC
    ENZYME, SOLUBLE||Malic enzyme,
    cytoplasmic||NADP-dependent malic
    enzyme||cytosolic malic enzyme
    1||MALATE DEHYDROGENASE,
    NADP(+)-DEPENDENT,
    SOLUBLE||malic enzyme 1,
    soluble||MALIC ENZYME, NADP(+)-
    DEPENDENT, CYTOSOLIC||malic
    enzyme 1, NADP(+)-dependent,
    cytosolic||
    ZNF365 ||ZNF365C||ZNF365D||KIAA0844||ZNF365 0.173 NM_199450 552
    ||TALN||talanin||ZNF365B||ZNF365
    ZNF365A||zinc finger protein
    365||zinc finger protein 365 isoform
    B||zinc finger protein 365 isoform
    C||zinc finger protein 365 isoform
    D||
    KRTAP3-2 ||KRTAP3-2||keratin associated 0.167 NM_031959 553
    protein 3-2||
    SYNPO2L ||SYNPO2L||synaptopodin 2-like|| 0.166 NM_024875 554
    BNIP3 ||BNIP3||BCL2/adenovirus E1B 0.166 NM_004052 555
    19 kD-interacting protein
    3||BCL2/adenovirus E1B 19 kDa
    interacting protein
    3||BCL2/ADENOVIRUS E1B 19-KD
    PROTEIN-INTERACTING PROTEIN
    3||BCL2/adenovirus E1B 19 kD
    interacting protein
    3||BCL2/adenovirus E1B 19-kDa
    protein-interacting protein 3||
    CRYAB ||CTPP2||CRYAB||CRYSTALLIN, 0.158 NM_001885 556
    ALPHA-B||CRYSTALLIN, ALPHA-
    2||crystallin, alpha B||heat-shock 20 kD
    like-protein||CRYA2 CATARACT,
    POSTERIOR POLAR 2||
    FLJ21511 ||FLJ21511||hypothetical protein 0.154 NM_025087 557
    FLJ21511||
    HIG2 ||HIG2||hypoxia-inducible protein 0.148 NM_013332 558
    2||
    SYNPO2L ||SYNPO2L||synaptopodin 2-like|| 0.139 NM_024875 559
    IGFL1 ||APRG644||UNQ644|| 0.138 NM_198541 560
    FLJ40201 ||FLJ40201||hypothetical protein 0.129 NM_152607 561
    FLJ40201||
    ECG2 ||ECG2||esophagus cancer-related 0.128 NM_032566 562
    gene-2||
    ALOX12 ||12(S)-lipoxygenase||12- 0.105 NM_000697 563
    @LIPOXYGENASE||1.13.11.31||ALOX12
    ||LOG12||12@LO||ARACHIDONATE
    12-
    OXIDOREDUCTASE||arachidonate
    12-lipoxygenase||
    EPB41L3 ||DAL1||KIAA0987||EPB41L3||4.1B|| 0.0956 NM_012307 564
    DAL-1||NONERYTHROID PROTEIN
    4.1, BRAIN TYPE||erythrocyte
    membrane protein band 4.1-like
    3||differentially expressed in
    adenocarcinoma of the lung||
    SNX19 ||KIAA0254||CHET8||SNX19||sorting 0.0946 NM_014758 565
    nexin 19||KIAA0254 gene
    product||
    P11 ||PRSS26-PENDING||P11||PP11||22 0.0934 NM_006025 566
    serine protease||26 serine
    protease||placental protein 11
    precursor||
    CES4 ||||CES1||carboxylesterase 1 0.0881 NM_016280 567
    (monocyte/macrophage serine
    esterase 1)||
    EPB41L3 ||DAL1||KIAA0987||EPB41L3||4.1B|| 0.0709 NM_012307 568
    DAL-1||NONERYTHROID PROTEIN
    4.1, BRAIN TYPE||erythrocyte
    membrane protein band 4.1-like
    3||differentially expressed in
    adenocarcinoma of the lung||
    EPB41L3 ||DAL1||KIAA0987||EPB41L3||4.1B|| 0.0687 NM_012307 569
    DAL-1||NONERYTHROID PROTEIN
    4.1, BRAIN TYPE||erythrocyte
    membrane protein band 4.1-like
    3||differentially expressed in
    adenocarcinoma of the lung||
    GYS2 ||GYS2||2.4.1.11||LIVER GLYCOGEN 0.0662 NM_021957 570
    SYNTHASE||GLYCOGEN SYNTHASE,
    LIVER||glycogen synthase 2 (liver)||
    CDA ||3.5.4.5||CDA||CDD||cytidine 0.0587 NM_001785 571
    deaminase||
    0.0555 BF514741 572
    0.0387 AK125406 573
    CRISP3 ||dJ442L6.3||CRS3||CRISP- 0.0306 NM_006061 574
    3||SGP28||Aeg2||CRISP3||cysteine-
    rich secretory protein-3||cysteine-
    rich secretory protein 3||specific
    granule protein (28 kDa)||
  • TABLE 2
    Patient characteristicsa
    Maximum
    Age Esophageal Eosinophil Expansion of Allergic
    Patient Sex (year) Disease Treatment number/hpf basal layer SPT/Ab SPT/Fb Diseasec
    1 M 11 NL None 0 No Unk Unk Unk
    2 F 9 NL None 0 No 1 3 Yes
    3 F 6 NL LTRA 0 No Unk Unk Unk
    4 F 13 NL None 0 No 0 0 No
    5 M 10 NL None 0 No Unk Unk Unk
    6 F 4 NL LTRA 0 No Unk Unk Unk
    7 M 6 CE PPI 0 Yes Unk Unk Unk
    8 M 17 CE PPI 0 Yes Unk Unk Unk
    9 F 14 CE LTRA 3 Yes 0 0 No
    10 F 12 CE None 3 Yes Unk Unk Unk
    11 F 11 CE LTRA + PPI 6 Yes Unk Unk Unk
    12 M 11 EE PPI 24 Yes 2 4 Yes
    13 F 4 EE PPI 25 Yes 0 0 No
    14 M 15 EE None 30 Yes 1 1 Yes
    15 M 15 EE None 31 Yes 2 0 Yes
    16 M 13 EE PPI 32 Yes 0 0 No
    17 M 6 EE PPI 40 Yes 3 1 Yes
    18 M 13 EE LTRA 42 Yes 4 4 Yes
    19 F 16 EE LTRA + PPI 50 Yes 0 0 No
    20 M 15 EE None 51 Yes 0 0 No
    21 M 3 EE PPI 56 Yes 1 4 Yes
    22 F 14 EE PPI 72 Yes 3 3 Yes
    23 M 2 EE None 83 Yes 0 4 Yes
    24 F 4 EE PPI 218 Yes 2 4 Yes
    aPatient characteristics at the time the biopsy sample was obtained.
    bThe number of positive skin prick test to foods (SPT/F) or aeroallergens (SPT/A) are reported on a 0-4 scale as described in the Methods.
    cHistory of past or present atopic dermatitis, allergic rhinitis, or asthma.
    Abbreviations:
    M, male;
    F, female;
    NL, normal;
    CE, Chronic Esophagitis;
    EE, Eosinophilic Esophagitis;
    LTRA, Leukotriene Receptor Antagonist;
    PPI, proton pump inhibitor;
    Unk, unknown.
  • TABLE 3
    Gene ontology of the upregulated genes in the EE transcript signature
    Classification COUNT %
    Total upregulated 344
    CLASSIFIED (biological process) 270 100
    RESPONSE TO PEST/PATHOGEN/PARASITE 26 9.6
    RESPONSE TO STRESS 30 11.1
    INFLAMMATORY RESPONSE 13 4.8
    POSITIVE REGULATION OF I-KAPPAB 8 3
    KINASE/NF-KAPPAB CASCADE
    RESPONSE TO WOUNDING 14 5.2
    POSITIVE REGULATION OF SIGNAL 8 3
    TRANSDUCTION
    CELL COMMUNICATION 70 25.8
    SIGNAL TRANSDUCTION 59 21.8
    RESPONSE TO BIOTIC STIMULUS 49 18.1
    PROTEIN KINASE CASCADE 12 4.4
    HUMORAL IMMUNE RESPONSE 9 3.3
    IMMUNE RESPONSE 44 16.2
    RESPONSE TO EXTERNAL STIMULUS 54 19.9
    APOPTOSIS 14 5.2
    CARBOXYLIC ACID BIOSYNTHESIS 5 1.8
    ORGANIC ACID BIOSYNTHESIS 5 1.8
    PROTEOLYSIS AND PEPTIDOLYSIS 17 6.3
    ICOSANOID METABOLISM 4 1.5
    MONOCARBOXYLIC ACID TRANSPORT 3 1.1
    CATABOLISM 22 8.1
    PROTEIN CATABOLISM 17 6.3
    COMPLEMENT ACTIVATION 4 1.5
    CELL ADHESION 17 6.3
    ANTIGEN PROCESSING, ENDOGENOUS 3 1.1
    ANTIGEN VIA MHC CLASS I
    MACROMOLECULE CATABOLISM 18 6.6
    FATTY ACID BIOSYNTHESIS 4 1.5
    ICOSANOID BIOSYNTHESIS 3 1.1
    FATTY ACID METABOLISM 6 2.2
    BLOOD COAGULATION 5 1.8
    HEMOSTASIS 5 1.8
    CHOLESTEROL METABOLISM 4 1.5
    LIPID METABOLISM 13 4.8
    ANION TRANSPORT 7 2.6
    STEROL METABOLISM 4 1.5
    REGULATION OF BODY FLUIDS 5 1.8
    CLASSIFIED (molecular function) 271 100
    SIGNAL TRANSDUCER ACTIVITY 60 22.1
    SCAVENGER RECEPTOR ACTIVITY 5 1.8
    OXIDOREDUCTASE ACTIVITY, ACTING ON 4 1.5
    THE CH—NH2
    GROUP OF DONORS
    PEPTIDE TRANSPORTER ACTIVITY 3 1.1
    PROTEIN BINDING 37 13.7
    PEPTIDASE ACTIVITY 16 5.9
    ENDOPEPTIDASE ACTIVITY 13 4.8
    CHYMOTRYPSIN ACTIVITY 6 2.2
    OBSOLETE MOLECULAR FUNCTION 15 5.5
    TRYPSIN ACTIVITY 6 2.2
    PROTEASOME ENDOPEPTIDASE ACTIVITY 3 1.1
    GLYCOSAMINOGLYCAN BINDING 5 1.8
    INTERLEUKIN RECEPTOR ACTIVITY 3 1.1
    RECEPTOR ACTIVITY 38 14
    INTERLEUKIN BINDING 3 1.1
    ENZYME ACTIVATOR ACTIVITY 6 2.2
    OLIGOPEPTIDE TRANSPORTER ACTIVITY 2 0.7
      • The functional annotations are generated by subjecting the data to DAVID software with the GoCharts (gene ontology charts) functional algorithm. Analysis is based on biological processes and molecular functions.
  • TABLE 4
    Gene ontology of the downregulated genes of the EE transcript signature
    Classification COUNT %
    Total downregulated 230
    CLASSIFIED (biological process) 180 100
    CARBOXYLIC ACID METABOLISM 11 6.1
    ORGANIC ACID METABOLISM 11 6.1
    METABOLISM 75 41.7
    INTRACELLULAR SIGNALING CASCADE 16 8.9
    FATTY ACID METABOLISM 5 2.8
    ICOSANOID METABOLISM 3 1.7
    MORPHOGENESIS 16 8.9
    PROTEIN KINASE CASCADE 6 3.3
    CLASSIFIED (molecular function) 180 100
    CATALYTIC ACTIVITY 63 35
    OXIDOREDUCTASE ACTIVITY, ACTING ON 6 3.3
    CH—OH GROUP OF DONORS
    ENZYME INHIBITOR ACTIVITY 8 4.4
    SERINE ESTERASE ACTIVITY 3 1.7
    ACTIN BINDING 7 3.9
    OXIDOREDUCTASE ACTIVITY 16 8.9
    CARBOXYLESTERASE ACTIVITY 3 1.7
    ENZYME REGULATOR ACTIVITY 11 6.1
    CYTOSKELETAL PROTEIN BINDING 7 3.9
    TRANS-1,2-DIHYDROBENZENE-1,2-DIOL 2 1.1
    DEHYDROGENASE ACTIVITY
    HYDROLASE ACTIVITY, ACTING ON ESTER 11 6.1
    BONDS
    ENDOPEPTIDASE INHIBITOR ACTIVITY 5 2.8
    PROTEASE INHIBITOR ACTIVITY 5 2.8
    CARBOXYLIC ACID TRANSPORTER ACTIVITY 4 2.2
    ORGANIC ACID TRANSPORTER ACTIVITY 4 2.2
    CYTOCHROME-B5 REDUCTASE ACTIVITY 2 1.1
    POLY(A) BINDING 2 1.1
    PHOSPHORIC MONOESTER HYDROLASE 6 3.3
    ACTIVITY
    PHOSPHOPROTEIN PHOSPHATASE ACTIVITY 5 2.8
    MAGNESIUM ION BINDING 5 2.8
      • The functional annotations are generated by subjecting the data to DAVID software with the GoCharts (gene ontology charts) functional algorithm. Analysis is based on biological processes and molecular functions.
  • TABLE 5
    Number of genes obtained using Welch and Student T-Test,
    Pearson correlation test and fold change filter.
    fold change
    fold change
    2 3 5 10
    NLvs EE 1146 382 124 42
    NLvs CE 25 7 0 0
    p value
    0.05 0.01 0.005 0.001
    NLvs EE
    Welch T test 9063 4183 3034 1527
    student T test 7707 3283 2295 1017
    Welch T test + FDR 1928 574 333 69
    student T test + FDR 958 236 134 59
    NLvs CE
    Welch T test 1432 163 73 8
    student T test 1618 216 105 8
    Welch T test + FDR 0 0 0 0
    student T test + FRD 0 0 0 0
    EE Atopic vs EE non-Atopic
    Welch T test 1403 200 90 13
    student T test 1543 216 88 14
    Welch T test + FDR 0 0 0 0
    student T test + FDR 0 0 0 0
    EE female vs EE male
    Welch T test 4158 857 434 75
    student T test 4185 691 298 49
    Welch T test + FDR 1 1 1 1
    student T test + FDR 8 5 5 5
    p value
    Pearson correlation 0.05 0.01 0.005 0.001 0.0005
    Correlation to eosinophils 6261 2757 1943 899 615
    Correlation to age 2257 334 136 16 10
    Abbreviation:
    False rate discovery correction (FDR);
    EE, Eosinophilic esophagitis;
    CE, Chronic esophagitis;
    NL, normal.
  • TABLE 6
    Genes significantly different in EE and CE compared to NL
    Fold Genbank
    Increase Accession
    Common Name Description in EE number
    2.432 AK095791
    LOC132430 2.047 XR_000195
    ARRDC2 ||CLONE24945||PP2703||ARRDC2|| 1.887 NM_015683
    arrestin domain containing 2||
    FGF11 ||FGF11||MGC45269||FHF3||fibroblast 1.868 NM_004112
    growth factor
    11||fibroblast
    growth factor homologous factor 3||
    DAPK2 ||DRP-1||DAPK2||death-associated 1.695 NM_014326
    protein kinase
    2||
    SLCO3A1 ||SLC21A11||OATP- 1.623 NM_013272
    D||SLCO3A1||OATP3A1||solute
    carrier organic anion transporter
    family, member 3A1||solute carrier
    family 21 (organic anion
    transporter), member 11||
    TCF4 ||SEF2-1B||TCF4||E2- 1.547 NM_003199
    2||ITF2||transcription factor
    4||IMMUNOGLOBULIN
    TRANSCRIPTION FACTOR
    2||transcription factor 4 isoform
    b||Transcription factor-4
    (immunoglobulin transcription
    factor-2)||
    MARVELD3 ||LOC91862||MRVLDC3||MARVEL 1.517 NM_052858
    (membrane-associating) domain
    containing 3||similar to RIKEN cDNA
    1810006A16 gene||
    EXT1 1.507 BX115875
    NF1 ||NFNS||WSS||NF1||VRNF||Neurofibromin 1.506 NM_000267
    (neurofibromatosis, type
    I)||VON RECKLINGHAUSEN DISEASE
    NEUROFIBROMIN||neurofibromin 1
    (neurofibromatosis, von
    Recklinghausen disease, Watson
    disease)||
    BAT8 ||Em:AF134726.3||BAT8||NG36/G9a 1.45 NM_006709
    ||NG36 protein||ankyrin repeat-
    containing protein||HLA-B-
    ASSOCIATED TRANSCRIPT 8||G9A
    histone methyltransferase||HLA-B
    associated transcript 8||HLA-B
    associated transcript 8 BAT8 isoform
    a||HLA-B associated transcript 8
    BAT8 isoform b||
    SMC5L1 1.332 BC035661
    KLK1 ||Klk6||KLKR||3.4.21.35||KLK1||KALLIKREIN, 1.28 NM_002257
    RENAL/PANCREATIC/SALIVARY||tissue
    kallikrein||renal/pancreas/salivary
    kallikrein||kallikrein 1
    preproprotein||kallikrein 1,
    renal/pancreas/salivary||glandular
    kallikrein
    1||kallikrein serine
    protease
    1||
    C21orf51 ||C21orf51||chromosome 21 open 1.263 NM_058182
    reading frame
    51||
    INSR ||INSR||insulin receptor||IRAN, 1.25 NM_000208
    TYPE A||DIABETES MELLITUS,
    INSULIN-RESISTANT, WITH
    ACANTHOSIS NIGRICANS, TYPE
    A||INSR INSULIN RECEPTOR,
    DEFECT IN, WITH INSULIN-
    RESISTANT DIABETES MELLITUS
    AND ACANTHOSIS NIGRICANS||
    ||||LOC400988 (LOC400988), 1.225 BC039374
    mRNA||
    PARC ||H7AP1||KIAA0708||PARC||UbcH7- 1.206 NM_015089
    associated protein 1||p53-
    ASSOCIATED PARKIN-LIKE
    CYTOPLASMIC PROTEIN||
    1.192 BC033938
    SLC35C2 ||SLC35C2||solute carrier family 35, 1.145 NM_173179
    member C2||
    ARHGEF12 ||ARHGEF12||PRO2792||KIAA0382|| 0.884 NM_015313
    LARG LARG/MLL FUSION
    GENE||leukemia-associated rho
    guanine nucleotide exchange
    factor||RHO GUANINE NUCLEOTIDE
    EXCHANGE FACTOR 12||Rho
    guanine nucleotide exchange factor
    (GEF) 12||RHO GUANINE
    NUCLEOTIDE EXCHANGE FACTOR,
    LEUKEMIA-ASSOCIATED LEUKEMIA-
    ASSOCIATED RHO GEF||
    ||||Similar to hypothetical protein 0.869 XM_292624
    4932411E22 (LOC342600), mRNA||
    MGC22014 ||MGC22014||hypothetical protein 0.864 AB007861
    MGC22014||
    MTA3 0.861 AW594033
    MCF2L ||ARHGEF14||KIAA0362||FLJ12122|| 0.851 NM_024979
    MCF2L||OST||DBL's big
    sister||MCF2 transforming
    sequence-like protein||guanine
    nucleotide exchange factor
    DBS||MCF.2 cell line derived
    transforming sequence-like||
    SLC25A30 ||LOC253512||hypothetical protein 0.844 AL832206
    LOC253512||
    TARP 0.843 AK026401
    0.842 BC044912
    0.84 BM723387
    CXorf6 ||CG1||CXorf6||F18 0.831 NM_005491
    GENE||chromosome X open reading
    frame
    6||
    PBX3 0.823 AK027170
    RQCD1 ||CNOT9||RQCD1||RCD1+||protein 0.811 NM_005444
    involved in sexual
    development||rcd1 (required for cell
    differentiation, S. pombe) homolog
    1||RCD1 required for cell||
    differentiation1 homolog (S. pombe)
    ||
    TBN ||TBN||taube nuss homolog 0.81 NM_138572
    (mouse)||
    DNCH1 ||DNCH1||HL- 0.802 NM_001376
    3||KIAA0325||Dnchc1||p22||DYHC||
    DHC1a||DNCL||DNECL||dynein,
    cytoplasmic-like||DYNEIN HEAVY
    POLYPEPTIDE,
    CYTOPLASMIC||dynein heavy chain,
    cytosolic||dynein, cytoplasmic,
    heavy polypeptide 1||DYNEIN,
    CYTOPLASMIC, HEAVY CHAIN 1||
    ||||LOC388952 (LOC388952), 0.793 XM_373986
    mRNA||
    LOC115110 0.78 AL359943
    SYNE2 ||DKFZP434H2235||Nesprin- 0.779 NM_015180
    2||SYNE2||NUANCE||SYNE-
    2||KIAA1011||nesprin 2||nucleus
    and actin connecting
    element||SYNAPTIC NUCLEAR
    ENVELOPE PROTEIN
    2||spectrin
    repeat containing, nuclear envelope
    2||NUCLEAR ENVELOPE SPECTRIN
    REPEAT PROTEIN
    2||synaptic nuclei
    expressed gene 2 isoform
    b||synaptic nuclei expressed gene 2
    isoform c||synaptic nuclei expressed
    gene 2 isoform d||synaptic nuclei
    expressed gene 2 isoform
    e||synaptic nuclei expressed gene 2
    isoform a||
    YWHAZ ||KCIP-1||14-3-3- 0.654 NM_145690
    ZETA||YWHAZ||phospholipase
    A2||14-3-3 zeta||BRAIN PROTEIN
    14-3-3, ZETA ISOFORM||protein
    kinase C inhibitor protein-
    1||TYROSINE 3-
    MONOOXYGENASE/TRYPTOPHAN 5-
    MONOOXYGENASE ACTIVATION
    PROTEIN, ZETA ISOFORM||tyrosine
    3-monooxygenase/tryptophan 5-
    monooxygenase activation protein,
    zeta polypeptide||tyrosine
    3/tryptophan 5-monooxygenase
    activation protein, zeta
    polypeptide||
    0.653 BE562274
    0.65 BM993105
    MYOZ1 ||MYOZ1||myozenin 1||CALSARCIN 0.452 NM_021245
    2||
  • TABLE 7
    Genotype and allele frequencies of the SNP + 2496 of the
    eotaxin-3 gene in EE patients and non EE patients.
    Patients with Normal
    SNP + EE Controls Odds ratio
    2496 (n = 96) (n = 177) (95% CI) P-value
    TT 50 (52.08%) 106 (59.89%)  1.00 NS
    TG 33 (34.38%) 67 (37.85%) 1.04 (0.59-1.85)  NS
    GG 13 (13.54%) 4 (2.26%) 6.89 (1.95-26.53) 0.0003*
    TG + 46 (47.92%) 71 (40.11%) 1.374 (0.833-2.266) NS
    GG
    T 133 (69.27%)  279 (78.81%)  1.00 0.0166*
    G 59 (30.73%) 75 (21.19%) 1.65 (1.09-2.51) 
  • TABLE 8
    Arachidonic Acid pathway related genes
    Fold Genbank
    Common change Accession
    Name Description in EE number
    ALOX15 ||1.13.11.33||ALOX15||arachidonate 15- 20.89 NM_001140
    lipoxygenase||15-@LIPOXYGENASE,
    RETICULOCYTE ARACHIDONATE||
    PGDS ||PGDS||5.3.99.2||prostaglandin-D 5.265 NM_014485
    synthase||prostaglandin D2 synthase,
    hematopoietic||hematopoietic prostaglandin
    D2 synthase||
    PTGES ||PGES||TP53I12||MGST1L1||PP1294||PP102 2.822 NM_198797
    ||PTGES||MGC10317||PIG12||MGST1-
    L1||MGST-IV||MGST1-like 1||p53-INDUCED
    GENE 12||prostaglandin E synthase||p53-
    induced apoptosis protein 12||prostaglandin
    E synthase isoform 2||prostaglandin E
    synthase isoform
    1||microsomal glutathione
    S-transferase 1-like 1||tumor protein p53
    inducible protein 12||
    LTA4H ||3.3.2.6||LTA4H||leukotriene A4 2.205 NM_000895
    hydrolase||
    PLA2G3 ||PLA2G3||phospholipase A2, group III|| 2.156 NM_015715
    PLA2G7 ||PAFAH||PLA2G7||LDL- 1.737 NM_005084
    PLA2||LIPOPROTEIN-ASSOCIATED
    PHOSPHOLIPASE A2 PLATELET-ACTIVATING
    FACTOR ACETYLHYDROLASE
    DEFICIENCY||phospholipase A2, group VII
    (platelet-activating factor acetylhydrolase,
    plasma)||
    PTGS2 ||COX2||PGHS2||1.14.99.1||PGHS- 1.718 NM_000963
    2||PTGS2||hCox-2||PGG/HS||PHS-
    2||CYCLOOXYGENASE 2||PROSTAGLANDIN
    G/H SYNTHASE 2||prostaglandin-
    endoperoxide synthase 2
    precursor||prostaglandin-endoperoxide
    synthase 2 (prostaglandin G/H synthase and
    cyclooxygenase)||
    ALOX5AP ||FLAP||ALOX5AP||5-@LIPOXYGENASE- 1.646 NM_001629
    ACTIVATING PROTEIN||MK-886-binding
    protein||FIVE-LIPOXYGENASE-ACTIVATING
    PROTEIN||arachidonate 5-lipoxygenase-
    activating protein||five-lipoxygenase
    activating protein||
    PTGDS ||PGDS2||PTGDS||PDS||5.3.99.2||prostaglandin- 1.475 NM_000954
    H2 D-isomerase||PGD2
    synthase||beta-trace protein||glutathione-
    independent PGD
    synthase||PROSTAGLANDIN D2 SYNTHASE,
    BRAIN||lipocalin-type prostaglandin D
    synthase||prostaglandin D2 synthase 21 kDa
    (brain)||
    PTGIS ||PGIS||5.3.99.4||PTGIS||CYP8A1||PROSTA 1.345 NM_000961
    CYCLIN SYNTHASE||PROSTAGLANDIN I2
    SYNTHASE||prostaglandin I2 (prostacyclin)
    synthase||
    PTGFRN ||SMAP-6||CD9P1||FPRP||KIAA1436||CD9P- 1.342 NM_020440
    1||FLJ11001||PTGFRN||EWI-F||FP
    REGULATORY PROTEIN||CD9 partner
    1||prostaglandin F2 receptor negative
    regulator||
    PTGDS ||PGDS2||PTGDS||PDS||5.3.99.2||prostaglandin- 1.334 NM_000954
    H2 D-isomerase||PGD2
    synthase||beta-trace protein||glutathione-
    independent PGD
    synthase||PROSTAGLANDIN D2 SYNTHASE,
    BRAIN||lipocalin-type prostaglandin D
    synthase||prostaglandin D2 synthase 21 kDa
    (brain)||
    PTGER4 ||EP4R||PTGER4||prostaglandin E2 1.33 NM_000958
    receptor||PGE receptor, EP4
    subtype||PROSTAGLANDIN E RECEPTOR 4,
    EP4 SUBTYPE||prostaglandin E receptor 4,
    subtype EP4||prostaglandin E receptor 4
    (subtype EP4)||
    PAFAH2 ||HSD-PLA2||PAFAH2||3.1.1.47||platelet- 1.329 NM_000437
    activating factor acetylhydrolase 2,
    40 kDa||platelet-activating factor
    acetylhydrolase 2 (40 kD)||
    HPGD ||PGDH1||15- 1.322 NM_000860
    PGDH||HPGD||hydroxyprostaglandin
    dehydrogenase 15-(NAD)||15-
    @HYDROXYPROSTAGLANDIN
    DEHYDROGENASE, TYPE I||
    PTGFRN ||SMAP-6||CD9P1||FPRP||KIAA1436||CD9P- 1.304 NM_020440
    1||FLJ11001||PTGFRN||EWI-F||FP
    REGULATORY PROTEIN||CD9 partner
    1||prostaglandin F2 receptor negative
    regulator||
    HPGD ||PGDH1||15- 1.252 NM_000860
    PGDH||HPGD||hydroxyprostaglandin
    dehydrogenase 15-(NAD)||15-
    @HYDROXYPROSTAGLANDIN
    DEHYDROGENASE, TYPE I||
    LTC4S ||MGC33147||LTC4S||2.5.1.37||LTC4 1.237 NM_000897
    SYNTHASE DEFICIENCY||leukotriene C4
    synthase||LTC4S LEUKOTRIENE C4
    SYNTHASE DEFICIENCY||leukotriene C4
    synthase isoform
    1||leukotriene C4
    synthase isoform
    2||
    PTGER2 ||PTGER2||Prostaglandin E receptor 2, EP2 1.171 NM_000956
    subtype, 53 kD||prostaglandin E receptor 2
    (subtype EP2), 53 kDa||
    PTGES ||PGES||TP53I12||MGST1L1||PP1294||PP102 1.146 NM_198797
    ||PTGES||MGC10317||PIG12||MGST1-
    L1||MGST-IV||MGST1-like 1||p53-INDUCED
    GENE 12||prostaglandin E synthase||p53-
    induced apoptosis protein 12||prostaglandin
    E synthase isoform 2||prostaglandin E
    synthase isoform
    1||microsomal glutathione
    S-transferase 1-like 1||tumor protein p53
    inducible protein 12||
    PLA2G4C ||cPLA2-gamma||PLA2G4C||cytosolic 1.133 NM_003706
    phospholipase A2 gamma||phospholipase
    A2, group IVC (cytosolic)||PHOSPHOLIPASE
    A2, CYTOSOLIC, CALCIUM-INDEPENDENT,
    GAMMA||phospholipase A2, group IVC
    (cytosolic, calcium-independent)||
    IGSF8 ||PGRL||IGSF8||CD81P3||PROSTAGLANDIN 1.124 NM_052868
    REGULATORY-LIKE||CD81 PARTNER
    3||immunoglobulin superfamily, member
    8||
    LTB4R ||BLTR||CMKRL1||BLT1||LTB4- 1.117 NM_000752
    R||LTB4R||GPR16||P2RY7||LTB4R1||LTBR1||
    PURINOCEPTOR P2Y7||P2Y purinoceptor
    7||Chemoattractant receptor-like
    1||leukotriene B4 receptor||G protein-
    coupled receptor 16||Leukotriene B4
    receptor
    1||LEUKOTRIENE B4 G PROTEIN-
    COUPLED RECEPTOR||PURINERGIC
    RECEPTOR P2Y, G PROTEIN-COUPLED,
    7||purinergic receptor P2Y, G-protein
    coupled, 7||leukotriene b4 receptor
    (chemokine receptor-like 1)||
    HPGD ||PGDH1||15- 1.115 NM_000860
    PGDH||HPGD||hydroxyprostaglandin
    dehydrogenase 15-(NAD)||15-
    @HYDROXYPROSTAGLANDIN
    DEHYDROGENASE, TYPE I||
    PTGDS ||PGDS2||PTGDS||PDS||5.3.99.2||prostaglandin- 1.106 NM_000954
    H2 D-isomerase||PGD2
    synthase||beta-trace protein||glutathione-
    independent PGD
    synthase||PROSTAGLANDIN D2 SYNTHASE,
    BRAIN||lipocalin-type prostaglandin D
    synthase||prostaglandin D2 synthase 21 kDa
    (brain)||
    PAFAH2 ||HSD-PLA2||PAFAH2||3.1.1.47||platelet- 1.105 NM_000437
    activating factor acetylhydrolase 2,
    40 kDa||platelet-activating factor
    acetylhydrolase 2 (40 kD)||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 1.104 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGDR ||MGC49004||PTGDR||PGD 1.101 NM_000953
    receptor||prostanoid DP
    receptor||prostaglandin D2 receptor (DP)||
    LYPLA2 ||LYPLA2||3.1.1.5||APT- 1.093 NM_007260
    2||DJ886K2.4||acyl-protein
    thioesterase||lysophospholipase II||
    LYPLA2 ||LYPLA2||3.1.1.5||APT- 1.093 NM_007260
    2||DJ886K2.4||acyl-protein
    thioesterase||lysophospholipase II||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 1.091 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGIR ||PTGIR||PRIPR||PGI receptor||prostacyclin 1.079 NM_000960
    receptor||prostanoid IP
    receptor||PROSTAGLANDIN I2
    RECEPTOR||prostaglandin I2 (prostacyclin)
    receptor (IP)||
    LTB4R2 ||||LTB4R2||leukotriene B4 receptor 2|| 1.076 NM_019839
    PLA2G4C ||cPLA2-gamma||PLA2G4C||cytosolic 1.074 NM_003706
    phospholipase A2 gamma||phospholipase
    A2, group IVC (cytosolic)||PHOSPHOLIPASE
    A2, CYTOSOLIC, CALCIUM-INDEPENDENT,
    GAMMA||phospholipase A2, group IVC
    (cytosolic, calcium-independent)||
    HPGD ||PGDH1||15- 1.067 NM_000860
    PGDH||HPGD||hydroxyprostaglandin
    dehydrogenase 15-(NAD)||15-
    @HYDROXYPROSTAGLANDIN
    DEHYDROGENASE, TYPE I||
    LYPLA2 ||LYPLA2||3.1.1.5||APT- 1.061 NM_007260
    2||DJ886K2.4||acyl-protein
    thioesterase||lysophospholipase II||
    TBXAS1 ||TS||TBXAS1||5.3.99.5||TXAS||TXA 1.057 NM_001061
    synthase||CYP5A1 THROMBOXANE
    SYNTHETASE DEFICIENCY||THROMBOXANE
    A SYNTHASE, PLATELET||thromboxane A
    synthase 1 (platelet, cytochrome P450,
    subfamily V)||thromboxane A synthase 1
    (platelet, cytochrome P450, family 5,
    subfamily A)||thromboxane A synthase 1
    (platelet, cytochrome P450, family 5,
    subfamily A) isoform TXS-II||
    PLA2G4D ||PLA2G4D||phospholipase A2, group IVD 1.049 NM_178034
    (cytosolic)||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 1.046 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    CYSLTR2 ||CYSLT2||CYSLTR2||cysteinyl leukotriene 1.035 NM_020377
    receptor
    2||
    PTGES2 ||PTGES2||PGES2||GBF1||GATE-BINDING 1.033 NM_198939
    FACTOR
    1||prostaglandin E synthase 2||
    TBXA2R ||TBXA2R||thromboxane A2 1.024 NM_201636
    receptor||THROMBOXANE A2 RECEPTOR,
    PLATELET||thromboxane A2 receptor
    isoform
    2||TBXA2R BLEEDING DISORDER
    DUE TO DEFECTIVE THROMBOXANE A2
    RECEPTOR||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 1.022 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 1.02 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 1.017 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGDR ||MGC49004||PTGDR||PGD 1.012 NM_000953
    receptor||prostanoid DP
    receptor||prostaglandin D2 receptor (DP)||
    TBXA2R ||TBXA2R||thromboxane A2 1.01 NM_201636
    receptor||THROMBOXANE A2 RECEPTOR,
    PLATELET||thromboxane A2 receptor
    isoform
    2||TBXA2R BLEEDING DISORDER
    DUE TO DEFECTIVE THROMBOXANE A2
    RECEPTOR||
    PLA2R1 ||PLA2IR||PLA2- 1.009 NM_007366
    R||PLA2R1||PLA2G1R||PHOSPHOLIPASE A2
    RECEPTOR, 180-KD|| phospholipase A2
    receptor
    1, 180 kDa||
    PLA2G10 ||GXPLA2||GXSPLA2||PLA2G10||phospholipase 1.008 NM_003561
    A2, group X||SECRETORY
    PHOSPHOLIPASE A2, GROUP
    X||PHOSPHOLIPASE A2, SECRETORY,
    CALCIUM-DEPENDENT, GROUP X||
    PTGFR ||MGC46203||PTGFR||PGF receptor||PGF2 1.006 NM_000959
    alpha receptor||prostaglandin receptor (2-
    alpha)||PROSTAGLANDIN RECEPTOR F(2-
    ALPHA)||prostanoid FP
    receptor||prostaglandin F2 alpha
    receptor||prostaglandin F receptor (FP)||
    PTGDR ||MGC49004||PTGDR||PGD 0.998 NM_000953
    receptor||prostanoid DP
    receptor||prostaglandin D2 receptor (DP)||
    PLA2G1B ||PLA2G1B||3.1.1.4||PPLA2||PLA2A||PHOSPHOLIPASE 0.989 NM_000928
    A2,
    PANCREATIC||PHOSPHOLIPASE A2
    POLYPEPTIDE A||phospholipase A2, group
    IB (pancreas)||
    PLA2G6 ||PLA2G6||iPLA2||PHOSPHOLIPASE A2, 0.988 NM_003560
    CALCIUM-INDEPENDENT||cytosolic,
    calcium-independent phospholipase
    A2||phospholipase A2, group VI (cytosolic,
    calcium-independent)||
    HTATIP ||PLIP||HTATIP||HTATIP1||TAT- 0.987 NM_182710
    INTERACTING PROTEIN, 60-KD||HIV-1 TAT-
    INTERACTING PROTEIN||cPLA2 interacting
    protein||TIP60 PLA2-INTERACTING
    PROTEIN||Tat interactive protein
    (60 kD)||HIV-1 Tat interactive protein,
    60 kDa||HIV-1 Tat interactive protein,
    60 kDa isoform 3||HIV-1 Tat interactive
    protein, 60 kDa isoform 2||HIV-1 Tat
    interactive protein, 60 kDa isoform 1||
    PLA2G5 ||3.1.1.4||PLA2G5||phospholipase A2, 0.983 NM_000929
    group V||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 0.983 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 0.981 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    ALOX15B ||ALOX15B||arachidonate 15-lipoxygenase, 0.967 NM_001141
    second type||15-@LIPOXYGENASE,
    RETICULOCYTE ARACHIDONATE, SECOND
    TYPE||
    CYSLTR1 ||HMTMF81||MGC46139||CYSLTR1||CYSLT1R 0.965 NM_006639
    ||HG55||LTD4 receptor||CysLTR vide
    supra||cysteinyl leukotriene receptor
    1||cysteinyl leukotriene D4 receptor||
    TBXA2R ||TBXA2R||thromboxane A2 0.963 NM_201636
    receptor||THROMBOXANE A2 RECEPTOR,
    PLATELET||thromboxane A2 receptor
    isoform
    2||TBXA2R BLEEDING DISORDER
    DUE TO DEFECTIVE THROMBOXANE A2
    RECEPTOR||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 0.962 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PLA2G12B ||PLA2G12B||phospholipase A2, group 0.961 NM_032562
    XIIB||
    LOC112868 ||||Similar to Group X secretory 0.957 AL390134
    phospholipase A2 precursor
    (Phosphatidylcholine 2-acylhydrolase GX)
    (GX sPLA2) (sPLA2-X) (LOC388229),
    mRNA||
    PTGER4 ||EP4R||PTGER4||prostaglandin E2 0.955 NM_000958
    receptor||PGE receptor, EP4
    subtype||PROSTAGLANDIN E RECEPTOR 4,
    EP4 SUBTYPE||prostaglandin E receptor 4,
    subtype EP4||prostaglandin E receptor 4
    (subtype EP4)||
    TBXAS1 ||TS||TBXAS1||5.3.99.5||TXAS||TXA 0.955 NM_001061
    synthase||CYP5A1 THROMBOXANE
    SYNTHETASE DEFICIENCY||THROMBOXANE
    A SYNTHASE, PLATELET||thromboxane A
    synthase 1 (platelet, cytochrome P450,
    subfamily V)||thromboxane A synthase 1
    (platelet, cytochrome P450, family 5,
    subfamily A)||thromboxane A synthase 1
    (platelet, cytochrome P450, family 5,
    subfamily A) isoform TXS-II||
    IPLA2(GAMMA); ||||IPLA2(GAMMA)||intracellular membrane- 0.951 XM_291241
    IPLA2-2 associated calcium-independent
    phospholipase A2 gamma||
    CYSLTR1 ||HMTMF81||MGC46139||CYSLTR1||CYSLT1R 0.949 NM_006639
    ||HG55||LTD4 receptor||CysLTR vide
    supra||cysteinyl leukotriene receptor
    1||cysteinyl leukotriene D4 receptor||
    PLA2R1 ||PLA2IR||PLA2- 0.948 NM_007366
    R||PLA2R1||PLA2G1R||PHOSPHOLIPASE A2
    RECEPTOR, 180-KD|| phospholipase A2
    receptor
    1, 180 kDa||
    LTB4R ||BLTR||CMKRL||BLT1||LTB4- 0.945 NM_000752
    R||LTB4R||GPR16||P2RY7||LTB4R1||LTBR1||
    PURINOCEPTOR P2Y7||P2Y purinoceptor
    7||Chemoattractant receptor-like
    1||leukotriene B4 receptor||G protein-
    coupled receptor 16||Leukotriene B4
    receptor
    1||LEUKOTRIENE B4 G PROTEIN-
    COUPLED RECEPTOR||PURINERGIC
    RECEPTOR P2Y, G PROTEIN-COUPLED,
    7||purinergic receptor P2Y, G-protein
    coupled, 7||leukotriene b4 receptor
    (chemokine receptor-like 1)||
    TBXA2R ||TBXA2R||thromboxane A2 0.944 NM_201636
    receptor||THROMBOXANE A2 RECEPTOR,
    PLATELET||thromboxane A2 receptor
    isoform
    2||TBXA2R BLEEDING DISORDER
    DUE TO DEFECTIVE THROMBOXANE A2
    RECEPTOR||
    PLA2G2D ||SPLASH||PLA2G2D||sPLA2S||secretory 0.943 NM_012400
    phospholipase A2s||SECRETORY-TYPE PLA,
    STROMA-ASSOCIATED
    HOMOLOG||phospholipase A2, group IID||
    LOC112868 ||||Similar to Group X secretory 0.943 AL390134
    phospholipase A2 precursor
    (Phosphatidylcholine 2-acylhydrolase GX)
    (GX sPLA2) (sPLA2-X) (LOC388229),
    mRNA||
    PLA2G5 ||3.1.1.4||PLA2G5||phospholipase A2, 0.94 NM_000929
    group V||
    PTGER3 ||MGC27302||PTGER3||prostanoid EP3 0.932 NM_198715
    receptor||prostaglandin receptor (PGE-
    2)||prostaglandin E2 receptor||PGE
    receptor, EP3 subtype||prostaglandin E
    receptor 3 (subtype EP3)||PROSTAGLANDIN
    E RECEPTOR 3, EP3
    SUBTYPE||prostaglandin E receptor 3,
    subtype EP3 isoform 7||prostaglandin E
    receptor
    3, subtype EP3 isoform
    8||prostaglandin E receptor 3, subtype EP3
    isoform 1||prostaglandin E receptor 3,
    subtype EP3 isoform 2||prostaglandin E
    receptor
    3, subtype EP3 isoform
    3||prostaglandin E receptor 3, subtype EP3
    isoform 4||prostaglandin E receptor 3,
    subtype EP3 isoform 5||prostaglandin E
    receptor
    3, subtype EP3 isoform 6||
    PTGER1 ||PTGER1||prostanoid EP1 receptor||PGE 0.932 NM_000955
    receptor, EP1 subtype||PROSTAGLANDIN E
    RECEPTOR 1, EP1 SUBTYPE||prostaglandin
    E receptor
    1, subtype EP1||prostaglandin E
    receptor 1 (subtype EP1), 42 kDa||
    PTGS1 ||PGHS- 0.929 NM_000962
    1||PTGHS||COX3||1.14.99.1||PGG/HS||PCOX1
    ||PHS1||PTGS1||CYCLOOXYGENASE
    1||PARTIAL COX1 PROTEINS||PGHS1
    CYCLOOXYGENASE 3||PROSTAGLANDIN
    G/H SYNTHASE 1||prostaglandin-
    endoperoxide synthase 1 isoform 2
    precursor||prostaglandin-endoperoxide
    synthase
    1 isoform 1
    precursor||prostaglandin-endoperoxide
    synthase 1 (prostaglandin G/H synthase and
    cyclooxygenase)||
    ALOX5 ||5- 0.926 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    PTGS1 ||PGHS- 0.921 NM_000962
    1||PTGHS||COX3||1.14.99.1||PGG/HS||PCOX1
    ||PHS1||PTGS1||CYCLOOXYGENASE
    1||PARTIAL COX1 PROTEINS||PGHS1
    CYCLOOXYGENASE 3||PROSTAGLANDIN
    G/H SYNTHASE 1||prostaglandin-
    endoperoxide synthase 1 isoform 2
    precursor||prostaglandin-endoperoxide
    synthase
    1 isoform 1
    precursor||prostaglandin-endoperoxide
    synthase 1 (prostaglandin G/H synthase and
    cyclooxygenase)||
    PTGS1 ||PGHS- 0.92 NM_000962
    1||PTGHS||COX3||1.14.99.1||PGG/HS||PCOX1
    ||PHS1||PTGS1||CYCLOOXYGENASE
    1||PARTIAL COX1 PROTEINS||PGHS1
    CYCLOOXYGENASE 3||PROSTAGLANDIN
    G/H SYNTHASE 1||prostaglandin-
    endoperoxide synthase 1 isoform 2
    precursor||prostaglandin-endoperoxide
    synthase
    1 isoform 1
    precursor||prostaglandin-endoperoxide
    synthase 1 (prostaglandin G/H synthase and
    cyclooxygenase)||
    H. sapiens H. sapiens EP4 prostaglandin receptor 0.912 BC042539
    EP4 pseudogene c16/g7
    prostaglandin
    receptor
    pseudogene
    c16/g7
    PLA2G2F ||PLA2G2F||phospholipase A2, group IIF|| 0.912 NM_022819
    PLAA ||PLAA||PLAP||PLA2P||phospholipase A2- 0.911 NM_004253
    activating protein||phospholipase A2
    activating protein||
    ALOXE3 ||ALOXE3||LOX TYPE 3||arachidonate 0.907 NM_021628
    lipoxygenase
    3||LIPOXYGENASE TYPE 3,
    EPIDERMAL||
    PTGS2 ||COX2||PGHS2||1.14.99.1||PGHS- 0.906 NM_000963
    2||PTGS2||hCox-2||PGG/HS||PHS-
    2||CYCLOOXYGENASE 2||PROSTAGLANDIN
    G/H SYNTHASE 2||prostaglandin-
    endoperoxide synthase 2
    precursor||prostaglandin-endoperoxide
    synthase 2 (prostaglandin G/H synthase and
    cyclooxygenase)||
    PLA2G6 ||PLA2G6||iPLA2||PHOSPHOLIPASE A2, 0.904 NM_003560
    CALCIUM-INDEPENDENT||cytosolic,
    calcium-independent phospholipase
    A2||phospholipase A2, group VI (cytosolic,
    calcium-independent)||
    ALOX12P2 ||ALOX12E||ALOX12P2||12-lipoxygenase- 0.899 AL832768
    related protein||arachidonate 12-
    lipoxygenase pseudogene 2||hair and skin
    epidermal-type 12-lipoxygenase-related
    pseudogene||
    PLA2G2E ||PLA2G2E||phospholipase A2, group IIE|| 0.899 NM_014589
    PTGIS ||PGIS||5.3.99.4||PTGIS||CYP8A1||PROSTA 0.897 NM_000961
    CYCLIN SYNTHASE||PROSTAGLANDIN I2
    SYNTHASE||prostaglandin I2 (prostacyclin)
    synthase||
    PLA2R1 ||PLA2IR||PLA2- 0.893 NM_007366
    R||PLA2R1||PLA2G1R||PHOSPHOLIPASE A2
    RECEPTOR, 180-KD|| phospholipase A2
    receptor
    1, 180 kDa||
    PLA2G5 ||3.1.1.4||PLA2G5||phospholipase A2, 0.891 NM_000929
    group V||
    IPLA2(GAMMA); ||||IPLA2(GAMMA)||intracellular membrane- 0.888 XM_291241
    IPLA2-2 associated calcium-independent
    phospholipase A2 gamma||
    PTGER1 ||PTGER1||prostanoid EP1 receptor||PGE 0.882 NM_000955
    receptor, EP1 subtype||PROSTAGLANDIN E
    RECEPTOR 1, EP1 SUBTYPE||prostaglandin
    E receptor
    1, subtype EP1||prostaglandin E
    receptor 1 (subtype EP1), 42 kDa||
    CYSLTR1 ||HMTMF81||MGC46139||CYSLTR1||CYSLT1R 0.876 NM_006639
    ||HG55||LTD4 receptor||CysLTR vide
    supra||cysteinyl leukotriene receptor
    1||cysteinyl leukotriene D4 receptor||
    PTGIS ||PGIS||5.3.99.4||PTGIS||CYP8A1||PROSTA 0.872 NM_000961
    CYCLIN SYNTHASE||PROSTAGLANDIN I2
    SYNTHASE||prostaglandin I2 (prostacyclin)
    synthase||
    PLA2G4B ||HsT16992||PLA2G4B||cPLA2- 0.867 NM_005090
    beta||PHOSPHOLIPASE A2, CYTOSOLIC,
    CALCIUM-DEPENDENT,
    BETA||phospholipase A2, group IVB
    (cytosolic)||
    PLA2R1 ||PLA2IR||PLA2- 0.858 NM_007366
    R||PLA2R1||PLA2G1R||PHOSPHOLIPASE A2
    RECEPTOR, 180-KD|| phospholipase A2
    receptor
    1, 180 kDa||
    ALOXE3 ||ALOXE3||LOX TYPE 3||arachidonate 0.855 NM_021628
    lipoxygenase
    3||LIPOXYGENASE TYPE 3,
    EPIDERMAL||
    SLCO2A1 ||OATP2A1||SLC21A2||SLCO2A1||PGT||solute 0.854 NM_005630
    carrier organic anion transporter family,
    member 2A1||solute carrier family 21
    (prostaglandin transporter), member 2||
    IPLA2(GAMMA); ||||IPLA2(GAMMA)||intracellular membrane- 0.853 XM_291241
    IPLA2-2 associated calcium-independent
    phospholipase A2 gamma||
    PLA2G12B ||PLA2G12B||phospholipase A2, group 0.844 NM_032562
    XIIB||
    PTGER1 ||PTGER1||prostanoid EP1 receptor||PGE 0.844 NM_000955
    receptor, EP1 subtype||PROSTAGLANDIN E
    RECEPTOR 1, EP1 SUBTYPE||prostaglandin
    E receptor
    1, subtype EP1||prostaglandin E
    receptor 1 (subtype EP1), 42 kDa||
    TBXA2R ||TBXA2R||thromboxane A2 0.838 NM_201636
    receptor||THROMBOXANE A2 RECEPTOR,
    PLATELET||thromboxane A2 receptor
    isoform
    2||TBXA2R BLEEDING DISORDER
    DUE TO DEFECTIVE THROMBOXANE A2
    RECEPTOR||
    PLA2G6 ||PLA2G6||iPLA2||PHOSPHOLIPASE A2, 0.833 NM_003560
    CALCIUM-INDEPENDENT||cytosolic,
    calcium-independent phospholipase
    A2||phospholipase A2, group VI (cytosolic,
    calcium-independent)||
    PLA2G6 ||PLA2G6||iPLA2||PHOSPHOLIPASE A2, 0.83 NM_003560
    CALCIUM-INDEPENDENT||cytosolic,
    calcium-independent phospholipase
    A2||phospholipase A2, group VI (cytosolic,
    calcium-independent)||
    ALOX5 ||5- 0.806 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    PTGS1 ||PGHS- 0.804 NM_000962
    1||PTGHS||COX3||1.14.99.1||PGG/HS||PCOX1
    ||PHS1||PTGS1||CYCLOOXYGENASE
    1||PARTIAL COX1 PROTEINS||PGHS1
    CYCLOOXYGENASE 3||PROSTAGLANDIN
    G/H SYNTHASE 1||prostaglandin-
    endoperoxide synthase 1 isoform 2
    precursor||prostaglandin-endoperoxide
    synthase
    1 isoform 1
    precursor||prostaglandin-endoperoxide
    synthase 1 (prostaglandin G/H synthase and
    cyclooxygenase)||
    ALOX15B ||ALOX15B||arachidonate 15-lipoxygenase, 0.773 NM_001141
    second type||15-@LIPOXYGENASE,
    RETICULOCYTE ARACHIDONATE, SECOND
    TYPE||
    ALOX5 ||5- 0.771 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    CYP4F2 ||CYP4F2||1.14.13.30||CPF2||leukotriene- 0.764 NM_001082
    B4 20-monooxygenase||LTB4 OMEGA-
    HYDROXYLASE, LIVER||LEUKOTRIENE B4
    OMEGA-HYDROXYLASE, LIVER||cytochrome
    P450, subfamily IVF, polypeptide
    2||cytochrome P450, family 4, subfamily F,
    polypeptide 2||
    CYP2J2 ||CPJ2||CYP2J2||1.14.14.1||microsomal 0.736 NM_000775
    monooxygenase||flavoprotein-linked
    monooxygenase||CYTOCHROME P450
    ARACHIDONIC ACID
    EPOXYGENASE||CYTOCHROME P450,
    SUBFAMILY IIJ, POLYPEPTIDE
    2||cytochrome P450, family 2, subfamily J,
    polypeptide 2||cytochrome P450, subfamily
    IIJ (arachidonic acid epoxygenase)
    polypeptide 2||
    CYP4F3 ||1.14.13.30||CYP4F3||CPF3||LTB4H||leukotriene- 0.727 NM_000896
    B4 20-monooxygenase||cytochrome
    P450-LTB-omega||LTB4 OMEGA-
    HYDROXYLASE||LEUKOTRIENE B4 OMEGA-
    HYDROXYLASE||cytochrome P450, family 4,
    subfamily F, polypeptide 3||cytochrome
    P450, subfamily IVF, polypeptide 3
    (leukotriene B4 omega hydroxylase)||
    PLA2G4B ||HsT16992||PLA2G4B||cPLA2- 0.71 NM_005090
    beta||PHOSPHOLIPASE A2, CYTOSOLIC,
    CALCIUM-DEPENDENT,
    BETA||phospholipase A2, group IVB
    (cytosolic)||
    ALOX5 ||5- 0.679 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    PLA2G4B ||HsT16992||PLA2G4B||cPLA2- 0.677 NM_005090
    beta||PHOSPHOLIPASE A2, CYTOSOLIC,
    CALCIUM-DEPENDENT,
    BETA||phospholipase A2, group IVB
    (cytosolic)||
    PLA2G2A ||PLA2G2A||MOM1||3.1.1.4||PLA2B||PLA2L|| 0.662 NM_000300
    PLAS1||PLA2S||PHOSPHOLIPASE A2,
    SYNOVIAL||PHOSPHOLIPASE A2
    POLYPEPTIDE B||MODIFIER OF MIN-1,
    MOUSE, HOMOLOG OF||phospholipase A2,
    group IIA (platelets, synovial fluid)||
    PLA2G12A ||PLA2G12A||phospholipase A2, group 0.656 NM_030821
    XIIA||
    ALOX5 ||5- 0.643 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    LTB4DH ||LTB4DH||MGC34943||leukotriene B4 12- 0.599 NM_012212
    hydroxydehydrogenase||NADP-dependent
    leukotriene B4 12-hydroxydehydrogenase||
    PLA2G12A ||PLA2G12A||phospholipase A2, group 0.578 NM_030821
    XIIA||
    ALOX12B ||ALOX12B||12R-LOX||12R- 0.549 NM_001139
    @LIPOXYGENASE||12-@LIPOXYGENASE, R
    TYPE||arachidonate 12-lipoxygenase, 12R
    type||ARACHIDONATE 12-LIPOXYGENASE,
    R TYPE||
    LTB4DH ||LTB4DH||MGC34943||leukotriene B4 12- 0.535 NM_012212
    hydroxydehydrogenase||NADP-dependent
    leukotriene B4 12-hydroxydehydrogenase||
    PLA2G4A ||3.1.1.4||3.1.1.5||cPLA2- 0.528 NM_024420
    alpha||PLA2G4A||PHOSPHOLIPASE A2,
    CYTOSOLIC, CALCIUM-DEPENDENT,
    ALPHA||phospholipase A2, group IVA
    (cytosolic, calcium-dependent)||
    CYP4F3 ||1.14.13.30||CYP4F3||CPF3||LTB4H||leukotriene- 0.476 NM_000896
    B4 20-monooxygenase||cytochrome
    P450-LTB-omega||LTB4 OMEGA-
    HYDROXYLASE||LEUKOTRIENE B4 OMEGA-
    HYDROXYLASE||cytochrome P450, family 4,
    subfamily F, polypeptide 3||cytochrome
    P450, subfamily IVF, polypeptide 3
    (leukotriene B4 omega hydroxylase)||
    LTB4DH ||LTB4DH||MGC34943||leukotriene B4 12- 0.358 NM_012212
    hydroxydehydrogenase||NADP-dependent
    leukotriene B4 12-hydroxydehydrogenase||
    AKR1C3 ||HA1753||1.1.1.188||DD3||hluPGFS||HSD17B5
    ||1.3.1.20||1.1.1.213||AKR1C3||KIAA0119
    ||HAKRB||HAKRe||trans-1,2-
    dihydrobenzene-1,2-diol
    dehydrogenase||chlordecone reductase
    homolog||dihydrodiol dehydrogenase
    3||prostaglandin F synthase||ALDO-KETO
    REDUCTASE B||3-@ALPHA-
    HYDROXYSTEROID DEHYDROGENASE, TYPE
    II||hydroxysteroid (17-beta) dehydrogenase
    5||type IIb 3-alpha hydroxysteroid
    dehydrogenases||aldo-keto redu..1f
    P450-LTB-omega||LTB4 OMEGA- 0.476 NM_000896
    HYDROXYLASE||LEUKOTRIENE B4 OMEGA-
    HYDROXYLASE||cytochrome P450, family 4,
    subfamily F, polypeptide 3||cytochrome
    P450, subfamily IVF, polypeptide 3
    (leukotriene B4 omega hydroxylase)||
    LTB4DH ||LTB4DH||MGC34943||leukotriene B4 12-
    hydroxydehydrogenase||NADP-dependent
    leukotriene B4 12
  • TABLE 9
    Mast cell related genes
    Fold Genbank
    Common Increase Accession
    Name Description in EE number
    ALOX15 ||1.13.11.33||ALOX15||arachidonate 20.89 NM_001140
    15-lipoxygenase||15-@LIPOXYGENASE,
    RETICULOCYTE ARACHIDONATE||
    CXCL1 ||MGSA-a||NAP- 18.79 NM_001511
    3||CXCL1||SCYB1||GROa||GRO1,
    FORMERLY||GRO PROTEIN,
    ALPHA||GRO1 ONCOGENE,
    FORMERLY||MELANOMA GROWTH
    STIMULATORY ACTIVITY, ALPHA||GRO1
    oncogene (melanoma growth-
    stimulating activity)||CHEMOKINE, CXC
    MOTIF, LIGAND 1||GRO1 oncogene
    (melanoma growth stimulating activity,
    alpha)||SMALL INDUCIBLE CYTOKINE
    SUBFAMILY B, MEMBER 1||chemokine
    (C—X—C motif) ligand 1 (melanoma
    growth stimulating activity, alpha)||
    CPA3 ||CAP3||3.4.17.1||carboxypeptidase A3 13.13 NM_001870
    (mast cell)||CARBOXYPEPTIDASE A3,
    MAST CELL||mast cell carboxypeptidase
    A3 precursor||
    IL8 ||NAP1||IL-8||LUCT/interleukin- 7.071 NM_000584
    8||LECT||K60||NAF||MONAP||LYNAP||TSG-
    1||b-
    ENAP||emoctakin||SCYB8||NAP-
    1||GCP1||IL8||MDNCF||GCP-
    1||CXCL8||AMCF-I||interleukin
    8||protein 3-10C||beta-
    thromboglobulin-like
    protein||neutrophil-activating protein
    1||interleukin 8 precursor||neutrophil-
    activating peptide 1||lymphocyte-
    derived neutrophil-activating factor||T
    cell chemotactic factor||monocyte-
    derived neutrophil chemotactic
    factor||CXC chemokine ligand
    8||monocyte derived neutrophil-
    activating protein||granulocyte
    chemotactic protein 1||small inducible
    cytokine subfamily B, member 8||
    TPSB2 ||||TPS1||tryptase, alpha|| 6.429 NM_003294
    HRH1 ||HRH1||H1-R||hisH1||histamine 6.191 NM_000861
    receptor H1||BPHS, MOUSE, HOMOLOG
    OF||histamine receptor, subclass H1||
    TPSB2 ||||TPS1||tryptase, alpha|| 6.028 NM_003294
    TPSB2 ||||TPS1||tryptase, alpha|| 5.573 NM_003294
    PGDS ||PGDS||5.3.99.2||prostaglandin-D 5.265 NM_014485
    synthase||prostaglandin D2 synthase,
    hematopoietic||hematopoietic
    prostaglandin D2 synthase||
    HS3ST1 ||HS3ST1||3OST1||2.8.2.23||heparin- 4.249 NM_005114
    glucosamine 3-O-
    sulfotransferase||heparan sulfate
    (glucosamine) 3-O-sulfotransferase
    1||heparan sulfate D-glucosaminyl 3-O-
    sulfotransferase 1 precursor||
    MS4A2 ||FCERI||MS4A1||MS4A2||FCER1B||Fc 4.192 NM_000139
    epsilon receptor I beta-chain||Fc IgE
    RECEPTOR, BETA CHAIN||MEMBRANE-
    SPANNING 4 DOMAINS, SUBFAMILY A,
    MEMBER 2||immunoglobulin E receptor,
    high affinity, beta polypeptide||Fc
    FRAGMENT OF IgE, HIGH AFFINITY I,
    RECEPTOR FOR, BETA
    SUBUNIT||membrane-spanning 4-
    domains, subfamily A, member 2 (Fc
    fragment of IgE, high affinity I, receptor
    for; beta polypeptide)||
    CXCR4 CXCR4 4.092 AJ224869
    TPSB2 ||||TPS1||tryptase, alpha|| 4.033 NM_003294
    TPSB2 ||||TPS1||tryptase, alpha|| 3.98 NM_003294
    PRG1 ||MGC9289||PPG||serglycin||PRG1||hematopoetic 3.444 NM_002727
    proteoglycan core
    peptide||platelet proteoglycan protein
    core||proteoglycan 1, secretory
    granule||secretory granule proteoglycan
    core peptide||proteoglycan 1, secretory
    granule precursor||proteoglycan protein
    core for mast cell secretory granule||
    PRG1 ||MGC9289||PPG||serglycin||PRG1||hematopoetic 3.441 NM_002727
    proteoglycan core
    peptide||platelet proteoglycan protein
    core||proteoglycan 1, secretory
    granule||secretory granule proteoglycan
    core peptide||proteoglycan 1, secretory
    granule precursor||proteoglycan protein
    core for mast cell secretory granule||
    TPSB2 ||||TPS1||tryptase, alpha|| 3.188 NM_003294
    ADAMDEC1 ||M12.219||ADAMDEC1||disintegrin 3.118 NM_014479
    protease||ADAM-like, decysin 1||ADAM-
    LIKE PROTEIN DECYSIN 1||A
    DISINTEGRIN AND
    METALLOPROTEINASE DOMAIN-LIKE
    PROTEIN DECYSIN
    1||
    TPSB2 ||||TPS1||tryptase, alpha|| 2.997 NM_003294
    IL15 ||IL-15||IL15||MGC9721||interleukin 2.879 NM_172174
    15||interleukin 15 isoform 2
    precursor||interleukin 15 isoform 1
    precursor||
    PTGES ||PGES||TP53I12||MGST1L1||PP1294||PP102 2.822 NM_198797
    ||PTGES||MGC10317||PIG12||MGST1-
    L1||MGST-IV||MGST1-like 1||p53-
    INDUCED GENE 12||prostaglandin E
    synthase||p53-induced apoptosis
    protein
    12||prostaglandin E synthase
    isoform
    2||prostaglandin E synthase
    isoform
    1||microsomal glutathione S-
    transferase 1-like 1||tumor protein p53
    inducible protein 12||
    KIT ||2.7.1.112||CD117||SCFR||PBT||KIT|| 2.754 NM_000222
    KIT ONCOGENE||STEM CELL FACTOR
    RECEPTOR||MAST CELL GROWTH
    FACTOR RECEPTOR||v-kit Hardy-
    Zuckerman 4 feline sarcoma viral
    oncogene homolog||v-kit Hardy-
    Zuckerman 4 feline sarcoma viral
    oncogene homolog precursor||
    VCAM1 ||VCAM1||INCAM-100||CD106 2.355 NM_001078
    antigen||vascular cell adhesion molecule
    1||vascular cell adhesion molecule 1
    isoform b precursor||vascular cell
    adhesion molecule
    1 isoform a
    precursor||
    ITGAM ||ITGAM||MAC1A||MO1A||CR3A||MAC- 2.246 NM_000632
    1||Mo1, ALPHA SUBUNIT||Mac1, ALPHA
    SUBUNIT||integrin alpha M
    precursor||neutrophil adherence
    receptor alpha-M subunit||COMPLEMENT
    RECEPTOR TYPE
    3, ALPHA
    SUBUNIT||Integrin, alpha-M
    (complement component receptor-3,
    alpha; antigen CD11B (p170);
    macrophage antigen, alpha
    polypeptide)||integrin, alpha M
    (complement component receptor 3,
    alpha; also known as CD11b (p170),
    macrophage antigen alpha
    polypeptide)||
    LTA4H ||3.3.2.6||LTA4H||leukotriene A4 2.205 NM_000895
    hydrolase||
    IL1F9 ||IL1H1||IL1F9||IL1RP2||INTERLEUKIN 2.109 NM_019618
    1-RELATED PROTEIN 2||INTERLEUKIN 1
    HOMOLOG 1||interleukin 1 family,
    member 9||
    FCER1G ||FCER1G||Fc IgE RECEPTOR, GAMMA 2.057 NM_004106
    CHAIN||immunoglobulin E receptor,
    high affinity, gamma
    chain||IMMUNOGLOBULIN E RECEPTOR,
    HIGH-AFFINITY, OF MAST CELLS,
    GAMMA POLYPEPTIDE||Fc fragment of
    IgE, high affinity I, receptor for; gamma
    polypeptide||Fc FRAGMENT OF IgE,
    HIGH AFFINITY I, RECEPTOR FOR,
    GAMMA SUBUNIT||Fc fragment of IgE,
    high affinity I, receptor for, gamma
    polypeptide precursor||
    IL18R1 ||IL-1Rrp||IL1RRP||IL18R1||IL1 2.047 NM_003855
    receptor-related protein||interleukin 18
    receptor 1||interleukin 18 receptor 1
    precursor||
    CCL18 ||CCL18||DC-CK1||AMAC1||AMAC- 2.003 NM_002988
    1||MIP-
    4||CKb7||PARC||DCCK1||SCYA18,
    FORMERLY||chemokine (C-C),
    dendritic||pulmonary and activation-
    regulated chemokine||CC chemokine
    ligand
    18||macrophage inflammatory
    protein
    4||dendritic cell chemokine
    1||small inducible cytokine A18
    precursor||CHEMOKINE, CC MOTIF,
    LIGAND 18||alternative macrophage
    activation-associated CC chemokine
    1||SMALL INDUCIBLE CYTOKINE
    SUBFAMILY A, MEMBER 18,
    FORMERLY||chemokine (C-C motif)
    ligand 18 (pulmonary and activation-
    regulated)||small inducible cytokine
    subfamily A (Cys-Cys), member 18||
    FCER1G ||FCER1G||Fc IgE RECEPTOR, GAMMA 2 NM_004106
    CHAIN||immunoglobulin E receptor,
    high affinity, gamma
    chain||IMMUNOGLOBULIN E RECEPTOR,
    HIGH-AFFINITY, OF MAST CELLS,
    GAMMA POLYPEPTIDE||Fc fragment of
    IgE, high affinity I, receptor for; gamma
    polypeptide||Fc FRAGMENT OF IgE,
    HIGH AFFINITY I, RECEPTOR FOR,
    GAMMA SUBUNIT||Fc fragment of IgE,
    high affinity I, receptor for, gamma
    polypeptide precursor||
    CCL18 ||CCL18||DC-CK1||AMAC1||AMAC- 1.933 NM_002988
    1||MIP-
    4||CKb7||PARC||DCCK1||SCYA18,
    FORMERLY||chemokine (C-C),
    dendritic||pulmonary and activation-
    regulated chemokine||CC chemokine
    ligand
    18||macrophage inflammatory
    protein
    4||dendritic cell chemokine
    1||small inducible cytokine A18
    precursor||CHEMOKINE, CC MOTIF,
    LIGAND 18||alternative macrophage
    activation-associated CC chemokine
    1||SMALL INDUCIBLE CYTOKINE
    SUBFAMILY A, MEMBER 18,
    FORMERLY||chemokine (C-C motif)
    ligand 18 (pulmonary and activation-
    regulated)||small inducible cytokine
    subfamily A (Cys-Cys), member 18||
    TGFBI ||CDG2||kerato-epithelin||BETA-IG- 1.92 NM_000358
    H3||CDB1||LCD1||CDGG1||CSD1||CSD2
    ||CSD3||TGFBI||BIGH3||KERATOEPITHELIN
    ||corneal
    dystrophy||TRANSFORMING GROWTH
    FACTOR, BETA-INDUCED, 68-
    KD||transforming growth factor, beta-
    induced, 68 kDa||
    CD209 ||CDSIGN||CD209||DC- 1.903 NM_021155
    SIGN1||DCSIGN||CD209 antigen||HIV
    GP120-BINDING PROTEIN||dendritic
    cell-specific ICAM3-grabbing
    nonintegrin||
    FGF11 ||FGF11||MGC45269||FHF3||fibroblast 1.868 NM_004112
    growth factor
    11||fibroblast growth
    factor homologous factor 3||
    TNFRSF5 ||Bp50||TNFRSF5||MGC9013||CDW40|| 1.862 NM_001250
    CD40 antigen||CD40L receptor||B CELL-
    ASSOCIATED MOLECULE CD40||CD40
    type II isoform||B cell surface antigen
    CD40||nerve growth factor receptor-
    related B-lymphocyte activation
    molecule||tumor necrosis factor
    receptor superfamily, member 5||tumor
    necrosis factor receptor superfamily,
    member 5 isoform 2 precursor||tumor
    necrosis factor receptor superfamily,
    member 5 isoform 1 precursor||
    C3AR1 ||HNFAG09||C3AR1||AZ3B||COMPLEMENT 1.843 NM_004054
    COMPONENT 3a RECEPTOR
    1||complement component 3 receptor
    1||
    IL15RA ||IL15RA||interleukin 15 receptor, 1.771 NM_172200
    alpha||interleukin 15 receptor, alpha
    isoform
    2||interleukin 15 receptor,
    alpha isoform 1 precursor||
    IL2RG ||IL2RG||IMD4||SCIDX1||CD132 1.739 NM_000206
    ANTIGEN||Interleukin-2 receptor,
    gamma||common cytokine receptor
    gamma chain||interleukin 2 receptor,
    gamma chain, precursor||interleukin 2
    receptor, gamma (severe combined
    immunodeficiency)||
    TNFRSF5 ||Bp50||TNFRSF5||MGC9013||CDW40|| 1.706 NM_001250
    CD40 antigen||CD40L receptor||B CELL-
    ASSOCIATED MOLECULE CD40||CD40
    type II isoform||B cell surface antigen
    CD40||nerve growth factor receptor-
    related B-lymphocyte activation
    molecule||tumor necrosis factor
    receptor superfamily, member 5||tumor
    necrosis factor receptor superfamily,
    member 5 isoform 2 precursor||tumor
    necrosis factor receptor superfamily,
    member 5 isoform 1 precursor||
    ALOX5AP ||FLAP||ALOX5AP||5-@LIPOXYGENASE- 1.646 NM_001629
    ACTIVATING PROTEIN||MK-886-binding
    protein||FIVE-LIPOXYGENASE-
    ACTIVATING PROTEIN||arachidonate 5-
    lipoxygenase-activating protein||five-
    lipoxygenase activating protein||
    IL12RB1 ||MGC34454||IL-12R- 1.588 NM_005535
    BETA1||IL12RB1||interleukin-12
    receptor beta-1 chain||IL-12 receptor
    beta component||INTERLEUKIN 12
    RECEPTOR, BETA-1||interleukin 12
    receptor, beta 1||interleukin 12
    receptor, beta 1 isoform 1
    precursor||interleukin 12 receptor, beta
    1 isoform 2 precursor||
    CCL5 ||TCP228||MGC17164||CCL5||D17S136E 1.56 NM_002985
    ||SIS-delta||SISd||SCYA5,
    FORMERLY||T CELL-SPECIFIC
    RANTES||beta-chemokine RANTES
    precursor||T-cell specific RANTES
    protein||T CELL-SPECIFIC PROTEIN
    p228||T-cell specific protein
    p288||CHEMOKINE, CC MOTIF, LIGAND
    5||SMALL INDUCIBLE CYTOKINE A5,
    FORMERLY||small inducible cytokine A5
    precursor||chemokine (C-C motif)
    ligand 5||small inducible cytokine
    subfamily A (Cys-Cys), member
    5||regulated upon activation, normally
    T-expressed, and presumably secreted||
    CCR1 ||CMKBR1||CCR1||MIP1aR||CKR- 1.525 NM_001295
    1||CKR1||HM145||MACROPHAGE
    INFLAMMATORY PROTEIN 1-
    ALPHA/RANTES RECEPTOR||chemokine
    (C-C motif) receptor 1||CHEMOKINE, CC
    MOTIF, RECEPTOR 1||
    GZMA ||HFSP||3.4.21.78||CTLA3||GZMA||CTL 1.509 NM_006144
    tryptase||granzyme A
    precursor||granzyme A (granzyme 1,
    cytotoxic T-lymphocyte-associated
    serine esterase 3)||CYTOLYTIC T CELL-
    AND NATURAL KILLER CELL-SPECIFIC
    TRYPSIN-LIKE SERINE
    PROTEASE||Granzyme A (Cytotoxic T-
    lymphocyte-associated serine esterase-
    3; Hanukah factor serine protease)||
    IFNAR2 ||IFNABR||IFNAR2||human interferon 1.503 NM_000874
    alpha/beta receptor||INTERFERON,
    ALPHA, BETA, AND OMEGA, RECEPTOR
    2||interferon (alpha, beta and omega)
    receptor 2||
    LTBP1 ||LTBP1||TGF-beta1-BP-1||LATENT 1.503 NM_000627
    TRANSFORMING GROWTH FACTOR-
    BETA-BINDING PROTEIN 1||latent
    transforming growth factor beta binding
    protein
    1||latent transforming growth
    factor beta binding protein 1 precursor||
    IFNGR1 ||IFNGR1||CD119 ANTIGEN||AVP, TYPE 1.498 NM_000416
    II||IMMUNE INTERFERON RECEPTOR
    1||interferon gamma receptor
    1||Immune interferon, receptor
    for||ANTIVIRAL PROTEIN, TYPE
    II||INTERFERON, GAMMA, RECEPTOR
    1||
    FCGR1A ||FCGR1A||FCRI||IGFR1||Fc-gamma 1.489 NM_000566
    receptor I A1||IMMUNOGLOBULIN G Fc
    RECEPTOR I||Fc fragment of IgG, high
    affinity Ia, receptor for (CD64)||
    ADORA3 ||||ADORA3||adenosine A3 receptor|| 1.481 NM_000677
    IL1RL1 ||ST2L||DER4||IL1RL1||ST2V||FIT- 1.479 NM_173459
    1||MGC32623||T1||ST2
    protein||interleukin 1 receptor-related
    protein||interleukin 1 receptor-like
    1||GROWTH STIMULATION-EXPRESSED
    GENE, MOUSE, HOMOLOG OF||homolog
    of mouse growth stimulation-expressed
    gene||interleukin 1 receptor-like 1
    isoform 1 precursor||interleukin 1
    receptor-like 1 isoform 2
    precursor||interleukin 1 receptor-like 1
    isoform 3 precursor||
    PTGDS ||PGDS2||PTGDS||PDS||5.3.99.2||prostaglandin- 1.475 NM_000954
    H2 D-isomerase||PGD2
    synthase||beta-trace
    protein||glutathione-independent PGD
    synthase||PROSTAGLANDIN D2
    SYNTHASE, BRAIN||lipocalin-type
    prostaglandin D synthase||prostaglandin
    D2 synthase
    21 kDa (brain)||
    CCL5 ||TCP228||MGC17164||CCL5||D17S136E 1.457 NM_002985
    ||SIS-delta||SISd||SCYA5,
    FORMERLY||T CELL-SPECIFIC
    RANTES||beta-chemokine RANTES
    precursor||T-cell specific RANTES
    protein||T CELL-SPECIFIC PROTEIN
    p228||T-cell specific protein
    p288||CHEMOKINE, CC MOTIF, LIGAND
    5||SMALL INDUCIBLE CYTOKINE A5,
    FORMERLY||small inducible cytokine A5
    precursor||chemokine (C-C motif)
    ligand 5||small inducible cytokine
    subfamily A (Cys-Cys), member
    5||regulated upon activation, normally
    T-expressed, and presumably secreted||
    HS3ST3A1 ||HS3ST3A1||2.8.2.23||3OST3A1||30ST3A1 1.441 NM_006042
    ||heparin-glucosamine 3-O-
    sulfotransferase||heparan sulfate D-
    glucosaminyl 3-O-sulfotransferase
    3A1||heparan sulfate (glucosamine) 3-
    O-sulfotransferase 3A1||
    CCL4 ||Act- 1.44 NM_002984
    2||MIP1B1||ACT2||LAG1||CCL4||MIP-1-
    beta||AT744.1||SCYA4,
    FORMERLY||lymphocyte-activation gene
    1||IMMUNE ACTIVATION
    2||MACROPHAGE INFLAMMATORY
    PROTEIN 1-BETA||SMALL INDUCIBLE
    CYTOKINE A4, FORMERLY||chemokine
    (C-C motif) ligand 4||CHEMOKINE, CC
    MOTIF, LIGAND 4||chemokine (C-C
    motif) ligand 4 precursor||small
    inducible cytokine A4 (homologous to
    mouse Mip-1b)||
    CXCR4 ||HM89||LAP3||NPYY3R||LESTR||HSY3RR 1.438 NM_003467
    ||CXCR4||WHIM||D2S201E||NPY3R||NPYR
    ||LIPOPOLYSACCHARIDE-
    ASSOCIATED PROTEIN 3||LEUKOCYTE-
    DERIVED SEVEN-TRANSMEMBRANE-
    DOMAIN RECEPTOR||LPS-ASSOCIATED
    PROTEIN
    3||SEVEN-TRANSMEMBRANE-
    SEGMENT RECEPTOR,
    SPLEEN||Neuropeptide Y receptor
    Y3||chemokine (C—X—C motif) receptor
    4||CHEMOKINE, CXC MOTIF, RECEPTOR
    4||chemokine (C—X—C motif), receptor 4
    (fusin)||
    CCL13 ||CCL13||MGC17134||NCC1||CK-beta- 1.435 NM_005408
    10||SCYL1||NCC-1||MCP-
    4||MCP4||CKb10||SCYA13,
    FORMERLY||new CC chemokine
    1||monocyte chemoattractant protein
    4||monocyte chemotactic protein
    4||chemokine (C-C motif) ligand
    13||CHEMOKINE, CC MOTIF, LIGAND
    13||small inducible cytokine A13
    precursor||SMALL INDUCIBLE
    CYTOKINE SUBFAMILY A, MEMBER 13,
    FORMERLY||small inducible cytokine
    subfamily A (Cys-Cys), member 13||
    CXCR4 ||HM89||LAP3||NPYY3R||LESTR||HSY3RR 1.427 NM_003467
    ||CXCR4||WHIM||D2S201E||NPY3R||NPYR
    ||LIPOPOLYSACCHARIDE-
    ASSOCIATED PROTEIN 3||LEUKOCYTE-
    DERIVED SEVEN-TRANSMEMBRANE-
    DOMAIN RECEPTOR||LPS-ASSOCIATED
    PROTEIN 3||SEVEN-TRANSMEMBRANE-
    SEGMENT RECEPTOR,
    SPLEEN||Neuropeptide Y receptor
    Y3||chemokine (C—X—C motif) receptor
    4||CHEMOKINE, CXC MOTIF, RECEPTOR
    4||chemokine (C—X—C motif), receptor 4
    (fusin)||
    IL8 ||NAP1||IL-8||LUCT/interleukin- 1.404 NM_000584
    8||LECT||K60||NAF||MONAP||LYNAP||TSG-
    1||b-
    ENAP||emoctakin||SCYB8||NAP-
    1||GCP1||IL8||MDNCF||GCP-
    1||CXCL8||AMCF-I||interleukin
    8||protein 3-10C||beta-
    thromboglobulin-like
    protein||neutrophil-activating protein
    1||interleukin 8 precursor||neutrophil-
    activating peptide 1||lymphocyte-
    derived neutrophil-activating factor||T
    cell chemotactic factor||monocyte-
    derived neutrophil chemotactic
    factor||CXC chemokine ligand
    8||monocyte derived neutrophil-
    activating protein||granulocyte
    chemotactic protein 1||small inducible
    cytokine subfamily B, member 8||
    MIST ||MIST||mast cell immunoreceptor 1.383 XM_093920
    signal transducer||
    IL2RB ||IL2RB||P70-75||CD122 1.381 NM_000878
    antigen||interleukin 2 receptor,
    beta||interleukin 2 receptor beta
    precursor||high affinity IL-2 receptor
    beta subunit||
    PTGDS ||PGDS2||PTGDS||PDS||5.3.99.2||prostaglandin- 1.334 NM_000954
    H2 D-isomerase||PGD2
    synthase||beta-trace
    protein||glutathione-independent PGD
    synthase||PROSTAGLANDIN D2
    SYNTHASE, BRAIN||lipocalin-type
    prostaglandin D synthase||prostaglandin
    D2 synthase
    21 kDa (brain)||
    CCL2 ||SMC- 1.307 NM_002982
    CF||CCL2||MCP1||MCAF||SCYA2||MCP-
    1||MGC9434||GDCF-2 HC11||monocyte
    chemoattractant protein-1||monocyte
    secretory protein JE||small inducible
    cytokine A2 precursor||monocyte
    chemotactic and activating
    factor||chemokine (C-C motif) ligand
    2||small inducible cytokine subfamily A
    (Cys-Cys), member 2||monocyte
    chemotactic protein 1, homologous to
    mouse Sig-je||
    CMA1 ||CYH||3.4.21.39||CMA1||MCT1||chymase, 1.263 NM_001836
    heart||chymase, mast cel||mast cell
    protease I||chymase 1, mast
    cell||chymase 1, mast cell
    preproprotein||
    GZMK ||TRYP2||GZMK||3.4.21.— 1.255 NM_002104
    ||PRSS||granzyme K
    precursor||granzyme K (serine
    protease, granzyme 3)||granzyme K
    (serine protease, granzyme 3; tryptase
    II)||
    PRG1 ||MGC9289||PPG||serglycin||PRG1||hematopoetic 1.23 NM_002727
    proteoglycan core
    peptide||platelet proteoglycan protein
    core||proteoglycan 1, secretory
    granule||secretory granule proteoglycan
    core peptide||proteoglycan 1, secretory
    granule precursor||proteoglycan protein
    core for mast cell secretory granule||
    KITLG ||KITLG||KL-1||SCF||SF||KIT 1.208 NM_000899
    ligand||STEEL FACTOR||STEEL, MOUSE,
    HOMOLOG OF||stem cell factor
    precursor||MGF STEM CELL
    FACTOR||mast cell growth factor||KIT
    ligand isoform a, precursor||KIT ligand
    isoform b, precursor||
    CXCL2 ||MIP2A||GROb||MGSA-b||MIP2- 1.194 NM_002089
    ALPHA||SCYB2||CXCL2||MIP-2a||CINC-
    2a||GRO2, FORMERLY||GRO PROTEIN,
    BETA||GRO2 ONCOGENE,
    FORMERLY||MACROPHAGE
    INFLAMMATORY PROTEIN 2||chemokine
    (C—X—C motif) ligand 2||CHEMOKINE,
    CXC MOTIF, LIGAND 2||SMALL
    INDUCIBLE CYTOKINE SUBFAMILY B,
    MEMBER 2||
    KITLG ||KITLG||KL-1||SCF||SF||KIT 1.169 NM_000899
    ligand||STEEL FACTOR||STEEL, MOUSE,
    HOMOLOG OF||stem cell factor
    precursor||MGF STEM CELL
    FACTOR||mast cell growth factor||KIT
    ligand isoform a, precursor||KIT ligand
    isoform b, precursor||
    FCER1A ||FCER1A||FCE1A||FcERI||Fc-epsilon 1.121 NM_002001
    RI-alpha||Fc IgE receptor, alpha
    polypeptide||Fc IgE RECEPTOR, ALPHA
    CHAIN||high affinity immunoglobulin
    epsilon receptor alpha-
    subunit||immunoglobulin E receptor,
    high-affinity, of mast cells, alpha
    polypeptide||Fc fragment of IgE, high
    affinity I, receptor for; alpha
    polypeptide||Fc FRAGMENT OF IgE,
    HIGH AFFINITY I, RECEPTOR FOR,
    ALPHA SUBUNIT||Fc fragment of IgE,
    high affinity I, receptor for; alpha
    polypeptide precursor||
    TGFB1 ||DPD1||TGFB1||TGF- 1.078 NM_000660
    BETA||CED||TRANSFORMING GROWTH
    FACTOR, BETA-1||diaphyseal dysplasia
    1, progressive (Camurati-Engelmann
    disease)||transforming growth factor,
    beta 1 (Camurati-Engelmann disease)||
    IL3 ||IL-3||IL3||MCGF||MULTI- 1.009 NM_000588
    CSF||multilineage-colony-stimulating
    factor||P-cell stimulating
    factor||hematopoietic growth
    factor||mast-cell growth
    factor||interleukin 3
    precursor||interleukin 3 (colony-
    stimulating factor, multiple)||
    KLRG1 ||KLRG1||MAFA-2F1||MAFAL||MAFA- 0.993 NM_005810
    LIKE||mast cell function-associated
    antigen (ITIM-containing)||MAST CELL
    FUNCTION-ASSOCIATED ANTIGEN, RAT,
    HOMOLOG OF||KILLER CELL LECTIN-
    LIKE RECEPTOR, SUBFAMILY G,
    MEMBER 1||killer cell lectin-like receptor
    subfamily G, member 1||
    TPSD1 ||TPSD1||mMCP-7-like-1||mMCP-7-like- 0.991 NM_012217
    2||hmMCP-7-like||mast cell
    tryptase||tryptase delta 1||
    MIST ||MIST||mast cell immunoreceptor 0.989 XM_093920
    signal transducer||
    TPSG1 ||TMT||3.4.21.59||PRSS31||TPSG1||pituitary 0.963 NM_012467
    tryptase||skin tryptase||lung
    tryptase||gamma II||mast cell
    tryptase||transmembrane tryptase
    preproprotein||tryptase gamma 1||mast
    cell protease II||
    TPSG1 ||TMT||3.4.21.59||PRSS31||TPSG1||pituitary 0.949 NM_012467
    tryptase||skin tryptase||lung
    tryptase||gamma II||mast cell
    tryptase||transmembrane tryptase
    preproprotein||tryptase gamma 1||mast
    cell protease II||
    IL9 ||IL-9||IL9||HP40||interleukin 9||p40 0.886 NM_000590
    protein||p40 cytokine||interleukin 9
    precursor||T-cell growth factor p40||T-
    CELL/MAST CELL GROWTH FACTOR
    P40||p40 T-cell and mast cell growth
    factor||homolog of mouse T cell and
    mast cell growth factor 40||
    IL1RAP ||IL- 0.764 NM_002182
    1RAcP||IL1R3||IL1RAP||IL1RAcP||interleukin
    1 receptor accessory
    protein||interleukin 1 receptor
    accessory protein isoform 1||interleukin
    1 receptor accessory protein isoform 2||
    IL1RL2 ||IL1R- 0.71 NM_003854
    rp2||IL1RL2||IL1RRP2||interleukin-1
    receptor-related protein 2||interleukin 1
    receptor-like 2||interleukin 1 receptor-
    like 2 precursor||
    FGFBP1 ||FGFBP1||HBP17||HBGF-BINDING 0.7 NM_005130
    PROTEIN, 17-KD||FGF-BINDING
    PROTEIN
    1||FIBROBLAST GROWTH
    FACTOR-BINDING PROTEIN
    1||HEPARIN-BINDING GROWTH
    FACTOR-BINDING PROTEIN, 17-
    KD||heparin-binding growth factor
    binding protein||
    ALOX5 ||5- 0.679 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    MCP ||MCP||MGC26544||TLX||MIC10||TRA2.10 0.645 NM_002389
    ||CD46 antigen||measles virus
    receptor||CD46 MEASLES,
    SUSCEPTIBILITY TO||complement
    membrane cofactor protein||trophoblast
    leucocyte common antigen||membrane
    cofactor protein isoform 6
    precursor||membrane cofactor protein
    isoform
    9 precursor||membrane
    cofactor protein isoform 11
    precursor||membrane cofactor protein
    isoform
    14 precursor||membrane
    cofactor protein isoform 2
    precursor||membrane cofactor protein
    isoform
    5 precursor||membrane
    cofactor protein isoform 8
    precursor||antigen identified by
    monoclonal antibody TRA-2-
    10||membrane cofactor protein isoform
    12 precursor||membrane cofactor
    protein isoform
    10
    precursor||membrane cofactor protein
    isoform
    13 precursor||membrane
    cofactor protein isoform 3
    precursor||membrane cofactor protein
    isoform
    1 precursor||membrane
    cofactor protein isoform 4
    precursor||membrane cofactor protein
    isoform
    7 precursor||membrane
    cofactor protein (CD46, trophoblast-
    lymphocyte cross-reactive antigen)||
    ALOX5 ||5- 0.643 NM_000698
    @LIPOXYGENASE||1.13.11.34||LOG5||5-
    @LO||ALOX5||arachidonate 5-
    lipoxygenase||
    HNMT ||HNMT||2.1.1.8||histamine N- 0.618 NM_006895
    methyltransferase||
    IL1A ||hematopoietin-1||IL1-ALPHA||IL- 0.606 NM_000575
    1A||IL1A||IL1F1||INTERLEUKIN 1-
    ALPHA||preinterleukin 1
    alpha||interleukin 1, alpha||interleukin
    1, alpha proprotein||
    HNMT ||HNMT||2.1.1.8||histamine N- 0.604 NM_006895
    methyltransferase||
    ALOX12B ||ALOX12B||12R-LOX||12R- 0.549 NM_001139
    @LIPOXYGENASE||12-
    @LIPOXYGENASE, R TYPE||arachidonate
    12-lipoxygenase, 12R
    type||ARACHIDONATE 12-
    LIPOXYGENASE, R TYPE||
    LTB4DH ||LTB4DH||MGC34943||leukotriene B4 0.535 NM_012212
    12-hydroxydehydrogenase||NADP-
    dependent leukotriene B4 12-
    hydroxydehydrogenase||
    PTN ||HARP||HBNF||NEGF1||PTN||HBGF8||heparin- 0.477 NM_002825
    binding growth-associated
    molecule||NEURITE OUTGROWTH-
    PROMOTING FACTOR, HEPARIN-
    BINDING||HEPARIN-BINDING GROWTH
    FACTOR
    8||heparin affin regulatory
    protein||pleiotrophin (heparin binding
    growth factor
    8, neurite growth-
    promoting factor 1)||
    CYP4F3 ||1.14.13.30||CYP4F3||CPF3||LTB4H||leukotriene- 0.476 NM_000896
    B4 20-
    monooxygenase||cytochrome P450-
    LTB-omega||LTB4 OMEGA-
    HYDROXYLASE||LEUKOTRIENE B4
    OMEGA-HYDROXYLASE||cytochrome
    P450, family 4, subfamily F, polypeptide
    3||cytochrome P450, subfamily IVF,
    polypeptide 3 (leukotriene B4 omega
    hydroxylase)||
    PDGFRA ||CD140a||Alpha platelet-derived 0.474 NM_006206
    growth factor receptor precursor
    IL1F6 ||FIL1E||IL-1F6||FIL1- 0.47 NM_014440
    EPSILON||IL1F6||FIL1(EPSILON)||interleukin
    1, epsilon||family of interleukin 1-
    epsilon||interleukin 1 family, member 6
    (epsilon)||
    PTN ||HARP||HBNF||NEGF1||PTN||HBGF8||heparin- 0.46 NM_002825
    binding growth-associated
    molecule||NEURITE OUTGROWTH-
    PROMOTING FACTOR, HEPARIN-
    BINDING||HEPARIN-BINDING GROWTH
    FACTOR
    8||heparin affin regulatory
    protein||pleiotrophin (heparin binding
    growth factor
    8, neurite growth-
    promoting factor 1)||
    FCER1A ||FCER1A||FCE1A||FcERI||Fc-epsilon 0.457 NM_002001
    RI-alpha||Fc IgE receptor, alpha
    polypeptide||Fc IgE RECEPTOR, ALPHA
    CHAIN||high affinity immunoglobulin
    epsilon receptor alpha-
    subunit||immunoglobulin E receptor,
    high-affinity, of mast cells, alpha
    polypeptide||Fc fragment of IgE, high
    affinity I, receptor for; alpha
    polypeptide||Fc FRAGMENT OF IgE,
    HIGH AFFINITY I, RECEPTOR FOR,
    ALPHA SUBUNIT||Fc fragment of IgE,
    high affinity I, receptor for; alpha
    polypeptide precursor||
    PTN ||HARP||HBNF||NEGF1||PTN||HBGF8||heparin- 0.435 NM_002825
    binding growth-associated
    molecule||NEURITE OUTGROWTH-
    PROMOTING FACTOR, HEPARIN-
    BINDING||HEPARIN-BINDING GROWTH
    FACTOR
    8||heparin affin regulatory
    protein||pleiotrophin (heparin binding
    growth factor 8, neurite growth-
    promoting factor 1)||
    IL1RN ||MGC10430||IL1RA||IL1RN||IRAP||ICIL- 0.43 NM_173843
    1RA||IL1F3||interleukin 1 receptor
    antagonist||intracellular IL-1 receptor
    antagonist type II||interleukin 1
    receptor antagonist isoform
    2||interleukin 1 receptor antagonist
    isoform
    3||interleukin 1 receptor
    antagonist isoform
    4||interleukin 1
    receptor antagonist isoform 1
    precursor||
    HNMT ||HNMT||2.1.1.8||histamine N- 0.421 NM_006895
    methyltransferase||
    IL12A ||NKSF1||IL12A||NFSK||IL- 0.405 NM_000882
    12A||CLMF||interleukin 12,
    p35||interleukin 12A precursor||IL12,
    SUBUNIT p35||IL-12, subunit
    p35||interleukin-12 alpha chain
    precursor||NF cell stimulatory factor
    chain
    1||NATURAL KILLER CELL
    STIMULATORY FACTOR, 35-KD
    SUBUNIT||natural killer cell stimulatory
    factor
    1, 35 kD subunit||interleukin 12A
    (natural killer cell stimulatory factor 1,
    cytotoxic lymphocyte maturation factor
    1, P35)||
    CXCL14 ||BMAC||NJAC||KS1||Kec||bolekine||CXCL14 0.394 NM_004887
    ||MGC10687||MIP-2g||SCYB14,
    FORMERLY||chemokine (C—X—C motif)
    ligand 14||small inducible cytokine B14
    precursor||CHEMOKINE, CXC MOTIF,
    LIGAND 14||CXC chemokine in breast
    and kidney||SMALL INDUCIBLE
    CYTOKINE SUBFAMILY B, MEMBER 14,
    FORMERLY||small inducible cytokine
    subfamily B (Cys-X-Cys), member 14
    (BRAK)||
    IL13RA1 ||IL-13Ra||IL13RA1||CD213a1 0.39 NM_001560
    antigen||INTERLEUKIN 13 RECEPTOR,
    ALPHA-1||IL13 receptor alpha-1
    chain||NR4, MOUSE, HOMOLOG
    OF||interleukin 13 receptor, alpha
    1||interleukin 13 receptor, alpha 1
    precursor||
    IL1RN ||MGC10430||IL1RA||IL1RN||IRAP||ICIL- 0.377 NM_173843
    1RA||IL1F3||interleukin 1 receptor
    antagonist||intracellular IL-1 receptor
    antagonist type II||interleukin 1
    receptor antagonist isoform
    2||interleukin 1 receptor antagonist
    isoform
    3||interleukin 1 receptor
    antagonist isoform
    4||interleukin 1
    receptor antagonist isoform 1
    precursor||
    LTB4DH ||LTB4DH||MGC34943||leukotriene B4 0.358 NM_012212
    12-hydroxydehydrogenase||NADP-
    dependent leukotriene B4 12-
    hydroxydehydrogenase||
    IL1F5 ||FIL1D||FIL1(DELTA)||IL1HY1||MGC29840 0.348 NM_012275
    ||IL1F5||FIL1-
    DELTA||IL1L1||IL1RP3||IL-1ra
    homolog||interleukin-1 HY1||interleukin
    1, delta||interleukin-1-like protein
    1||IL-1 related protein 3||family of
    interleukin 1-delta||interleukin-1
    receptor antagonist homolog
    1||interleukin 1 family, member 5
    (delta)||INTERLEUKIN 1 RECEPTOR
    ANTAGONIST HOMOLOG 1||
    IL18 ||IL-1g||IGIF||IL1F4||MGC12320||IL- 0.341 NM_001562
    18||IL18||interleukin-1 gamma||IL-1
    gamma||interleukin 18
    proprotein||interleukin 18 (interferon-
    gamma-inducing factor)||
    IL8RB ||IL8R2||IL8RA||IL8RB||CMKAR2||CDw128b 0.214 NM_001557
    ||GRO/MGSA
    receptor||CHEMOKINE (C—X—C)
    RECEPTOR 2||chemokine (CXC)
    receptor 2||interleukin 8 receptor
    beta||interleukin 8 receptor,
    beta||interleukin 8 receptor type
    2||INTERLEUKIN 8 RECEPTOR, TYPE
    2||high affinity interleukin-8 receptor
    B||CXCR2 gene for IL8 receptor type B||
    ALOX12 ||12(S)-lipoxygenase||12- 0.105 NM_000697
    @LIPOXYGENASE||1.13.11.31||ALOX12
    ||LOG12||12@LO||ARACHIDONATE 12-
    OXIDOREDUCTASE||arachidonate 12-
    lipoxygenase||

Claims (17)

1. A method comprising:
determining an expression profile of at least one gene selected from at least one of SEQ ID NOS. 1-574 that is activated or inhibited in an esophagus of a human patient,
comparing the patient's expression profile of the at least one gene with a human expression profile for the gene in eosinophilic esophagitis, and
determining that the patient has a propensity for eosinophilic esophagitis if there is a difference in relative expression between the at least one gene in the patient and in the human gene expression profile.
2. The method of claim 1 wherein a gene cluster is compared.
3. The method of claim 1 wherein the gene is selected from the group consisting of Chemokine (C-C motif) ligand 26, periostin, osteoblast specific factor, tumor necrosis factor, alpha-induced protein 6, cadherin-like 26; arachidonate 15-lipoxygenase, pro-melanin-concentrating hormone, chemokine (C-X-C motif) ligand 1, immunoglobulin lambda joining 3, transmembrane protein 16A, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, immunoglobulin heavy constant gamma 1 (Glm marker), FLJ16025 protein, ubiquitin D, immunoglobulin J polypeptide, linker protein for immunoglobulin, hypothetical protein FLJ33069, carboxypeptidase A3 (mast cell), similar to immunoglobulin kappa light chain variable region 011, Charcot-Leyden crystal protein, hypothetical protein MGC27165, pleckstrin homology-like domain, family B, member 2, hypothetical protein F1123259, immunoglobulin kappa constant, epiplakinl, chemokine (C-X-C motif) ligand 6, filaggrin, erythrocyte membrane protein band 4.1-like 3, sorting nexin 19, 26 serine protease, carboxylesterase 1 (monocyte/macrophage serine esterase 1), glycogen synthase 2 (liver), cytidine deaminase, GSGL541, or cysteine-rich secretory protein 3.
4. A method to enhance differentiation between eosinophilic esophagitis and chronic esophagitis, the method comprising:
determining signature esophageal gene transcripts for each of eosinophilic esophagitis and chronic esophagitis, the gene transcript encoding a cellular function selected from the group consisting of cell growth, cell maintenance, cell communication, cell response to stress, cell signal transduction, cell response to external stimulus, or cell immune response, and
determining the difference in each of eosinophilic esophagitis and chronic esophagitis signature esophageal gene transcripts to distinguish eosinophilic esophagitis from chronic esophagitis.
5. The method of claim 4 wherein the transcript is selected from SEQ ID NOS: 1-574.
6. The method of claim 4 wherein the transcript is a signature for a mast cell gene.
7. The method of claim 4 wherein the transcript is selected from the group consisting of Chemokine (C-C motif) ligand 26, periostin, osteoblast specific factor, tumor necrosis factor, alpha-induced protein 6, cadherin-like 26; arachidonate 15-lipoxygenase, pro-melanin-concentrating hormone, chemokine (C-X-C motif) ligand 1, immunoglobulin lambda joining 3, transmembrane protein 16A, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, immunoglobulin heavy constant gamma 1 (Glm marker), FLJ16025 protein, ubiquitin D, immunoglobulin J polypeptide, linker protein for immunoglobulin, hypothetical protein FLJ33069, carboxypeptidase A3 (mast cell), similar to immunoglobulin kappa light chain variable region 011, Charcot-Leyden crystal protein, hypothetical protein MGC27165, pleckstrin homology-like domain, family B, member 2, hypothetical protein F1123259, immunoglobulin kappa constant, epiplakinl, chemokine (C-X-C motif) ligand 6, filaggrin, erythrocyte membrane protein band 4.1-like 3, sorting nexin 19, 26 serine protease, carboxylesterase 1 (monocyte/macrophage serine esterase 1), glycogen synthase 2 (liver), cytidine deaminase, GSGL541, cysteine-rich secretory protein 3, and combinations thereof.
8. The method of claim 7 wherein the transcript induced to the greatest extent in eosinophilic esophagitis is eotaxin-3.
9. The method of claim 8 wherein the level of eotaxin-3 transcript positively correlates with eosinophilic esophagitis severity.
10. The method of claim 8 wherein the level of eotaxin-3 transcript positively correlates with blood eosinophil levels.
11. The method of 6 wherein a single nucleotide polymorphism of +2496 (G/T) in a gene for eotaxin-3 is a marker for the patient's susceptibility to eosinophilic esophagitis.
12. (canceled)
13. (canceled)
14. A method to differentiate eosinophilic esophagitis from chronic esophagitis, the method comprising:
determining a level of an eotaxin-3 transcript in a patient biological sample, determining whether the patient's eotaxin-3 transcript level is increased over an eotaxin-3 level in a control,
the patient having an increased risk for eosinophilic esophagitis versus chronic esophagitis with an increased level of the eotaxin-3 transcript in the patient sample.
15. (canceled)
16. (canceled)
17. (canceled)
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