{"entity":{"id":"stat3","kind":"target","name":"STAT3","aka":["signal transducer and activator of transcription 3","Signal transducer and activator of transcription 3"],"tldr":"STAT3 (Signal transducer and activator of transcription 3) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Leukaemia, Skin cancer and 5 more.","summary":"Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 4 variants. Open Targets scores its association with cancer at 0.78 (direct and indirect evidence; datatypes clinical 0.19, affected pathway 0.84, literature 1.00, genetic association 0.15, somatic mutation 0.97). IntOGen calls it a driver in 7 cohorts (7 activating, 0 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Lymphoid Neoplasm, Malignant Lymphoma, Non-Hodgkin Lymphoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11364","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11364"},{"label":"UniProt P40763","url":"https://www.uniprot.org/uniprotkb/P40763/entry"},{"label":"NCBI Gene 6774","url":"https://www.ncbi.nlm.nih.gov/gene/6774"},{"label":"Ensembl ENSG00000168610","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000168610"},{"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","leukaemia","skin-cancer","lung-cancer","ovarian","biliary-tract-cancer","dlbcl","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["inflammation-nfkb","jak-stat","nsclc-signalling","rtk-activation"],"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: Open Targets known-drug datatype score 0.19; IntOGen calls it an activating (Act) driver in 7 cohorts; CIViC holds 2 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.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: T-cell Large Granular Lymphocyte Leukaemia.","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":"STAT3","role":["drug-target","oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11364","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11364","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P40763","url":"https://www.uniprot.org/uniprotkb/P40763/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene STAT3","url":"https://civicdb.org/features/5516","note":"2 evidence items, 0 assertions, 4 variants; diseases: Diffuse Large B-cell Lymphoma, T-cell Large Granular Lymphocyte Leukaemia (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000168610","url":"https://platform.opentargets.org/target/ENSG00000168610/associations","note":"association with cancer (MONDO_0004992) 0.78; per-cancer scores at or above 0.5: ovarian cancer 0.52, acute lymphoblastic leukaemia 0.51, diffuse large B-cell lymphoma 0.54, non-Hodgkin lymphoma 0.75, skin cancer 0.57, lung cancer 0.57 (GraphQL API, CC0)"},{"label":"IntOGen STAT3","url":"https://www.intogen.org/search?gene=STAT3","note":"driver in 7 cohorts (Act 7, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"immune-microenvironment","distribution":"many-types","specificityNote":"Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA STAT3: RNA low tissue specificity; high antibody staining in 2 normal tissues. Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Leukaemia, Skin cancer (all types), Lung cancer (all types), Ovarian cancer, Biliary tract cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (STAT3-related early-onset multisystem autoimmune disease). (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas STAT3 tissue","url":"https://www.proteinatlas.org/ENSG00000168610-STAT3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt P40763","url":"https://www.uniprot.org/uniprotkb/P40763/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000168610 associations","url":"https://platform.opentargets.org/target/ENSG00000168610/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11364","ensembl":"ENSG00000168610","uniprot":"P40763","entrez":"6774","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Akira et al, Cell, 1994, \"Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7512451/","biology":"Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Upon activation of IL6ST/gp130 signalling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acetylation promotes its transcription activity and cell differentiation while deacetylation and oxidation of lysine residues by LOXL3 inhibits differentiation. Location: Cytoplasm; Nucleus (UniProt). Locus 17q21.2 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.75 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 3 cohorts (LNM, MLYM, NHL)","Leukaemia: Open Targets association 0.68 with leukaemia (MONDO_0005059)","Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)","Lung cancer: Open Targets association 0.57 with lung cancer (MONDO_0008903)","Ovarian cancer: Open Targets association 0.52 with ovarian cancer (MONDO_0008170)","Biliary tract cancer: Open Targets association 0.51 with biliary tract cancer (MONDO_0003060)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/stat3/","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":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"hepatosplenic-t-cell-lymphoma","kind":"cancer","name":"Hepatosplenic T-cell lymphoma","route":"/cancers/hepatosplenic-t-cell-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"sezary-syndrome","kind":"cancer","name":"Sezary syndrome","route":"/cancers/sezary-syndrome/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"},{"id":"t-large-granular-lymphocytic-leukaemia","kind":"cancer","name":"T-cell large granular lymphocytic leukaemia","route":"/cancers/t-large-granular-lymphocytic-leukaemia/"}],"pathway":[{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"},{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"},{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"drug":[{"id":"napabucasin","kind":"drug","name":"Napabucasin","route":"/drugs/napabucasin/"}]}}