Table I:
Functional annotation of the consensus atopy module
| Function/Pathway | Gene symbol | Chromosome | Gene name |
|---|---|---|---|
| Apoptosis | BCL2 | 18q21.33 | B-cell CLL/lymphoma 2 |
| BTG1a | 12q22 | B-cell translocation gene 1 | |
| CASP3 | 4q34 | Caspase 3 | |
| STK17B | 2q32.3 | Serine/threonine kinase 17b; DRAK2 | |
|
| |||
| Inflammation and | CD200R1 | 3q13.2 | CD200 receptor 1 |
| immunoregulation | CISH | 3p21.3 | Cytokine inducible SH2-containing protein |
| CSF1 | 1p21-p13 | Colony stimulating factor 1 | |
| IL-1F6a, b | 2q12-q14.1 | Interleukin 1 family, member 6 (epsilon) | |
| LIF | 22q12.2 | Leukemia inhibitory factor | |
| SOCS2 | 12q | Suppressor of cytokine signaling 2 | |
|
| |||
| Leukotriene and | ALOX5 | 10q11.2 | Arachidonate 5-lipoxygenase |
| Prostaglandin signaling | HPGD | 4q34-q35 | Hydroxyprostaglandin dehydrogenase |
| PTGER2 | 14q22 | Prostaglandin E receptor 2 (EP2 receptor) | |
|
| |||
| Protease activity and | PITRM1a | 10p15.2 | Pitrilysin metallopeptidase 1 |
| regulation | SPINT2 | 19q13.1 | Serine peptidase inhibitor, Kunitz type, 2 |
| TPP2a, b | 13q32-q33 | Tripeptidyl peptidase II | |
|
| |||
| Protein trafficking | RAB19Ba | 7q34 | GTP-binding protein RAB19B (RAB19) |
| RAB27B | 18q21.2 | RAB27B, member RAS oncogene family | |
| RAB30 | 11q12-q14 | RAB30, member RAS oncogene family | |
|
| |||
| Signal transduction | ARRDC2a, b | 19p13.11 | Arrestin domain containing 2 |
| CNKSR2a | Xp22.12 | Connector enhancer of kinase suppressor of Ras 2 | |
| KPNA6a | 1p35.1-p34.3 | Karyopherin alpha 6 (importin alpha 7) | |
| NCOA3 | 20q12 | Nuclear receptor coactivator 3 | |
| NDFIP2 | 13q31.1 | Nedd4 family interacting protein 2 | |
| NSMCE1 | 16p12.1 | Non-SMC element 1 homolog | |
| PGM1a | 1p31 | Phosphoglucomutase 1 | |
| RAP2Bb | 3q25.2 | RAP2B, member of RAS oncogene family | |
| RASL11Aa | 13q12.2 | RAS-like, family 11, member A | |
| SOCS2 | 12q | Suppressor of cytokine signaling 2 | |
| TBC1D1a | 4p14 | TBC1 domain family, member 1 | |
|
| |||
| Solute carrier activity | SLC26A11a | 17q25.3 | Solute carrier family 26, member 11 |
| SLC37A3 | 7q34 | Solute carrier family 37, member 3 | |
| SLC39A8 | 4q22-q24 | Solute carrier family 39, member 8 | |
|
| |||
| TcR signaling | APBB1IPa, b | 19p13.11 | Arrestin domain containing 2 |
| CEACAM1 | 19q13.2 | Carcinoembryonic antigen-related cell adhesion 1 | |
| CISH | 3p21.3 | Cytokine inducible SH2-containing protein | |
| DPP4 | 2q24.3 | Dipeptidyl-peptidase 4 (CD26) | |
| IL-2R | 10p15-p14 | Interleukin 2 receptor, alpha | |
| ITK | 5q31-q32 | IL2-inducible T-cell kinase | |
| LCP2b | 5q33.1-qter | Lymphocyte cytosolic protein 2 (SLP-76) | |
| MAL | 2cen-q13 | Mal, T-cell differentiation protein | |
| RAP1A | 1p13.3 | RAP1A, member of RAS oncogene family | |
|
| |||
| Th2 regulation and | CCL1 | 17q12 | C-C chemokine ligand 1, I-309 |
| function | GFI1 | 1p22 | Growth factor independent 1 |
| ID2 | 2p25 | Inhibitor of DNA binding 2 | |
| IL-13 | 5q31 | Interleukin 13 | |
| IL-17RB | 3p21.1 | Interleukin 17 receptor B (IL-25 receptor) | |
| IL-4R | 16p11.2–12.1 | Interleukin 4 receptor | |
| IL-5 | 5q31.1 | Interleukin 5 | |
| ITK | 5q31-q32 | IL2-inducible T-cell kinase | |
| RRS1b | 8q13.1 | RRS1 ribosome biogenesis regulator homolog | |
|
| |||
| Treg expression and | CISH | 3p21.3 | Cytokine inducible SH2-containing protein |
| function | FOXP3 | Xp11.23 | Forkhead box P3 |
| GFI1 | 1p22 | Growth factor independent 1 | |
| HIPK2 | 7q32-q34 | Homeodomain interacting protein kinase 2 | |
| IKZF4a, b | 12q13 | IKAROS family zinc finger 4 (Eos) | |
| IL-2R | 10p15-p14 | Interleukin 2 receptor, alpha | |
| ITK | 5q31-q32 | IL2-inducible T-cell kinase | |
| PTGER2 | 14q22 | Prostaglandin E receptor 2 (EP2 receptor) | |
| SOCS2 | 12q | Suppressor of cytokine signaling 2 | |
| TIAM1a | 21q22.1 | T-cell lymphoma invasion and metastasis 1 | |
|
| |||
| Transcriptional regulation | BATFa, b | 14q24.3 | Basic leucine zipper transcription factor, ATF-like |
| ENO1a, b | 1p36.3-p36.2 | Enolase 1, (alpha) | |
| HIPK1a | 1p13.2 | Homeodomain interacting protein kinase 1 | |
| ID2 | 2p25 | Inhibitor of DNA binding 2 | |
| IKZF1b | 7p13-p11.1 | IKAROS family zinc finger 1 (Ikaros) | |
| IKZF4a, b | 12q13 | IKAROS family zinc finger 4 (Eos) | |
| KLF3b | 4p14 | Kruppel-like factor 3 (basic) | |
| LASS6a | 2q24.3 | LAG1 homolog, ceramide synthase 6 | |
| PCGF5b | 10q23.32 | Polycomb group ring finger 5 | |
| TSC22D3b | Xq22.3 | TSC22 domain family, member 3; GILZ | |
|
| |||
| Wnt/β-catenin signaling | BCL9La, b | 11q23.3 | B-cell CLL/lymphoma 9-like |
| CAMK2D | 4q26 | Calcium-dependent protein kinase II delta | |
| DACT1 | 14q23.1 | Dapper homolog 1 | |
| HIPK2 | 7q32-q34 | Homeodomain interacting protein kinase 2 | |
| ID2 | 2p25 | Inhibitor of DNA binding 2 | |
| MEOX1a | 17q21 | Mesenchyme homeobox 1 | |
| TIAM1a | 21q22.1 | T-cell lymphoma invasion and metastasis 1 | |
|
| |||
| Unclassified or unknown | ETNK1a | 12p12.1 | Ethanolamine kinase 1 |
| function | FAM102Ba | 1p13.3 | Family with sequence similarity 102, member B |
| GNPDA1a | 5q21 | Glucosamine-6-phosphate deaminase 1 | |
| IMMT | 2p11.2 | Inner membrane protein, mitochondrial (mitofilin) | |
| OBFC2Aa | 2q32.3 | Oligonucleotide-binding fold containing 2A | |
| PLXDC1 | 17q21.1 | Plexin domain containing 1 | |
| SNTB1 | 8q23-q24 | Syntrophin, beta 1 | |
Genes were assigned to functional classes (NB: some genes in more than one class) based on classifications from the Gene Ontology consortium (http://www.geneontology.org/), as well as manual curation based on information from the literature and other sources. See Table S2 for additional information and references.
a
Novel genes which have not been previously reported in the context of atopy or Th2 regulation.
b
Genes which were specifically detected as atopy-associated based on their patterns of interconnectivity with other members of the atopy module, but were not detected as atopy-associated by differential expression analyses in Fig.1B.