Protein / target

Signal transducer and activator of transcription 3

Encoded bySTAT3P40763Homo sapiensSwiss-Prot

UniProt: P40763 Ensembl: ENSG00000168610 HGNC: HGNC:11364 NCBI Gene: 6774

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Transcription cis-regulatory region binding

Strongest disease association

Autoimmune Diseases

Via encoding gene STAT3 · Genetic literature evidence · score 0.82

Therapeutic position

Clinically advancing target

Research activity

Emerging research

16 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.

View complete UniProt function annotation

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:11294841, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18242580, PubMed:18782771, PubMed:22306293, PubMed:23084476, PubMed:28262505, PubMed:32929201, PubMed:38404237). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18782771, PubMed:28262505, PubMed:32929201). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). 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 (PubMed:28065600, PubMed:28262505). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC3 and NFATC4, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471)

Subcellular location

CytoplasmNucleus

Domains and Gene Ontology detail (123)

Domains & features

SH2

Gene Ontology

Cchromatin
Ccytoplasm
Ccytosol
Cglutamatergic synapse
Cmitochondrial inner membrane
Cnucleoplasm
Cnucleus
Cplasma membrane
Cpostsynaptic density
CRNA polymerase II transcription regulator complex
CSchaffer collateral - CA1 synapse
Ctranscription regulator complex

770 aa · 88 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingGOCell proliferation & survivalGOCell migrationGONuclear receptor signallingGOImmune signallingUniProt · GOTranscriptional regulationUniProt · GO

View supporting evidence

Synaptic signalling

·glutamatergic synapse
·postsynaptic density
·Schaffer collateral - CA1 synapse
·modulation of chemical synaptic transmission

Cell proliferation & survival

·regulation of cell population proliferation

Cell migration

·positive regulation of cell migration

Nuclear receptor signalling

·nuclear receptor activity

Immune signalling

·Signal transducer and transcription activator that mediates cellular responses to interl…
·cellular response to interleukin-17
·cytokine-mediated signaling pathway
·inflammatory response

Transcriptional regulation

·Signal transducer and transcription activator that mediates cellular responses to interl…
·RNA polymerase II transcription regulator complex
·transcription regulator complex
·DNA-binding transcription activator activity, RNA polymerase II-specific

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene STAT3

Gene-level evidence surfaced through the gene STAT3 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Autoimmune Diseases

0.79Well supported

Genetic evidence dominant · Open Targets 0.76

Crohn's Disease

0.72Moderately supported

Genetic evidence dominant · Open Targets 0.52

Lymphoma, Large B-Cell, Diffuse

0.51Moderately supported

Somatic mutation evidence dominant · Open Targets 0.49

Neoplasms

0.48Preliminary

Pathway evidence dominant · Open Targets 0.62 · no direct causal or clinical evidence

Neurodegenerative Diseases

0.34Preliminary

Pathway evidence dominant · Open Targets 0.49 · no direct causal or clinical evidence

View evidence synthesis (5)

Autoimmune DiseasesWell supported

0.79

agreement 0.65–0.92

Genetic95%Literature5%Genetic literaturedup

Open Targets aggregate 0.76 · 2 independent evidence families · 1 not counted as duplicate

Crohn's DiseaseModerately supported

0.72

agreement 0.58–0.85

Genetic91%Literature9%Genetic literaturedup

Open Targets aggregate 0.52 · 2 independent evidence families · 1 not counted as duplicate

Lymphoma, Large B-Cell, DiffuseModerately supported

0.51

agreement 0.39–0.63

Somatic mutation63%Literature24%Clinical13%

Open Targets aggregate 0.49 · 3 independent evidence families

NeoplasmsPreliminary

0.48

agreement 0.30–0.66

Pathway72%Literature28%

Open Targets aggregate 0.62 · 2 independent evidence families · no direct causal or clinical evidence

Neurodegenerative DiseasesPreliminary

0.34

agreement 0.17–0.52

Pathway90%Literature10%

Open Targets aggregate 0.49 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Autoimmune Diseases0.76

Neoplasms0.62

Crohn's Disease0.52

Lymphoma, Large B-Cell, Diffuse0.49

Neurodegenerative Diseases0.49

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)

DANVATIRSENPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (go cc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)

SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC med confPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.