# STAT3

Source: https://onco.cc/targets/stat3/  
OnCo record `stat3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: signal transducer and activator of transcription 3; Signal transducer and activator of transcription 3
- Tags: cancer-genes-wave
- Symbol: STAT3
- Class: oncogene
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:11364: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11364
- UniProt P40763: https://www.uniprot.org/uniprotkb/P40763/entry
- NCBI Gene 6774: https://www.ncbi.nlm.nih.gov/gene/6774
- Ensembl ENSG00000168610: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000168610
- Kucuk et al., Nat Commun 2015: activating STAT3 and STAT5B mutations in lymphomas derived from NK or gamma-delta T cells: https://doi.org/10.1038/ncomms7025
- 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: https://doi.org/10.1182/blood-2010-05-282780

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)](https://onco.cc/cancers/cutaneous-t-cell-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Hepatosplenic T-cell lymphoma](https://onco.cc/cancers/hepatosplenic-t-cell-lymphoma/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Sezary syndrome](https://onco.cc/cancers/sezary-syndrome/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/), [T-cell large granular lymphocytic leukaemia](https://onco.cc/cancers/t-large-granular-lymphocytic-leukaemia/)
- pathways: [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [JAK-STAT signalling](https://onco.cc/pathways/jak-stat/), [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- drugs: [Napabucasin](https://onco.cc/drugs/napabucasin/)

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