{"entity":{"id":"stat6","kind":"target","name":"STAT6","aka":["signal transducer and activator of transcription 6","Signal transducer and activator of transcription 6","D12S1644","IL-4-STAT"],"tldr":"STAT6 (Signal transducer and activator of transcription 6) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma and Diffuse large B-cell lymphoma.","summary":"Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signalling.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.58 (direct and indirect evidence; datatypes literature 0.98, animal model 0.31, genetic association 0.08, somatic mutation 0.89). IntOGen calls it a driver in 4 cohorts (4 activating, 0 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma, Non-Hodgkin Lymphoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11368","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11368"},{"label":"UniProt P42226","url":"https://www.uniprot.org/uniprotkb/P42226/entry"},{"label":"NCBI Gene 6778","url":"https://www.ncbi.nlm.nih.gov/gene/6778"},{"label":"Ensembl ENSG00000166888","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166888"},{"label":"Kucuk et al., Nat Commun 2015: activating STAT3 and STAT5B mutations in lymphomas derived from NK or gamma-delta T cells","url":"https://doi.org/10.1038/ncomms7025"},{"label":"Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma","url":"https://doi.org/10.1182/blood-2010-05-282780"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 4 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Lymphoma, JAK-STAT, in NK/T-cell lymphoma and in Hodgkin lymphoma: STAT3 and STAT5B mutations lock the transcription factor in its phosphorylated form. The STAT5B N642H substitution increases the binding affinity of the phosphotyrosine for the mutant histidine, so the phosphorylated protein persists and binds its target sites far more, and the growth advantage it gives can be partly reversed by a JAK1/2 inhibitor in the laboratory (Kucuk 2015). In Hodgkin lymphoma and primary mediastinal B-cell lymphoma the pathway is switched on from the other end, by amplification of JAK2 inside the 9p24.1 amplicon and by loss of the brakes SOCS1 and PTPN1. Frequency: Activating STAT3 and STAT5B mutations across 51 NK/T-cell lymphomas and 43 gamma-delta T-cell lymphomas, with STAT5B N642H particularly frequent in the gamma-delta group (Kucuk 2015). JAK2 sits in the 9p24.1 amplicon in Hodgkin lymphoma and mediastinal large B-cell lymphoma, and its amplification raises both protein and activity and specifically induces PD-1 ligand transcription (Green 2010). What it changes about treatment: Not through an approved drug. JAK inhibitors have been tested in both settings without becoming standard; the practical consequence of the Hodgkin and mediastinal finding is that it explains why checkpoint blockade works there."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"STAT6","role":["oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11368","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11368","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P42226","url":"https://www.uniprot.org/uniprotkb/P42226/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene STAT6","url":"https://civicdb.org/features/5520","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000166888","url":"https://platform.opentargets.org/target/ENSG00000166888/associations","note":"association with cancer (MONDO_0004992) 0.58; per-cancer scores at or above 0.5: diffuse large B-cell lymphoma 0.51, non-Hodgkin lymphoma 0.65 (GraphQL API, CC0)"},{"label":"IntOGen STAT6","url":"https://www.intogen.org/search?gene=STAT6","note":"driver in 4 cohorts (Act 4, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"one-type","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA STAT6: RNA low tissue specificity; high antibody staining in 6 normal tissues; highest cancer staining thyroid cancer (3 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Lymphoma); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P42226","url":"https://www.uniprot.org/uniprotkb/P42226/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene STAT6","url":"https://civicdb.org/features/5520","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen STAT6","url":"https://www.intogen.org/search?gene=STAT6","note":"driver in 4 cohorts (Act 4, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas STAT6 tissue","url":"https://www.proteinatlas.org/ENSG00000166888-STAT6/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000166888 associations","url":"https://platform.opentargets.org/target/ENSG00000166888/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11368","ensembl":"ENSG00000166888","uniprot":"P42226","entrez":"6778","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Hou et al, Science, 1994, \"An interleukin-4-induced transcription factor: IL-4 Stat\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8085155/","biology":"Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signalling. Location: Cytoplasm; Nucleus (UniProt). Locus 12q13.3 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.65 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Diffuse large B-cell lymphoma: Open Targets association 0.51 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/stat6/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"}]}}