Aliases: APRF.
STAT3 (Signal transducer and activator of transcription 3) is a latent cytoplasmic transcription factor that is activated by tyrosine phosphorylation (Tyr705) in response to cytokines and growth factors. Upon phosphorylation by JAK kinases, STAT3 forms dimers via reciprocal SH2 domain-phosphotyrosine interactions, translocates to the nucleus, binds DNA via its DNA-binding domain at GAS (gamma-activated sequence) elements, and regulates transcription of target genes involved in cell proliferation, survival, differentiation, and immune responses. STAT3 is a central mediator of the JAK-STAT signaling pathway, particularly downstream of IL-6 family cytokines (IL-6, LIF, CNTF, IL-11). The protein contains an N-terminal domain, coiled-coil domain, DNA-binding domain, linker domain, SH2 domain, and C-terminal transactivation domain. Serine phosphorylation (Ser727) modulates transcriptional activity and contributes to non-canonical mitochondrial functions (mitoSTAT3). STAT3 plays critical roles in immune regulation, inflammation, embryonic development, and is frequently constitutively activated in various cancers where it promotes oncogenic programs. In neural development, STAT3 promotes gliogenesis and astrocyte differentiation. ISOFORM BIOLOGY - Alternative splicing produces STAT3alpha (P40763-1, 770 AA) and STAT3beta (P40763-2, 722 AA). STAT3beta lacks the C-terminal transactivation domain (TAD) and can act as a dominant-negative for some alpha-specific target genes, but also has distinct transcriptional activities. The alpha/beta ratio modulates cellular responses, with STAT3beta showing tumor-suppressive functions in some contexts.
Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.
| Disorder | Relationship | Where the gene appears |
|---|---|---|
| Aggressive NK-cell Leukemia | somatic driver somatic |
mechanism: JAK-STAT Pathway Activation
|
| Anaplastic Large Cell Lymphoma | somatic driver somatic |
mechanism: JAK/STAT3 Activation in Systemic ALK-Negative ALCL
scoped to subtype: Systemic ALK-Negative
|
| Autoimmune Enteropathy | causative germline | |
| Breast Implant-Associated Anaplastic Large Cell Lymphoma | somatic driver somatic |
mechanism: JAK/STAT Activation in BIA-ALCL
|
| Chronic Mucocutaneous Candidiasis | causative germline |
mechanism: Loss of the Th17-Inducing Transcriptional Program
|
| Evans Syndrome | causative germline |
mechanism: Loss of Lymphocyte Self-Tolerance
|
| Gastrointestinal Lymphoma | somatic driver somatic | |
| Ankylosing Spondylitis |
untyped
GWAS
|
mechanism: IL-23/IL-17 Axis Activation
|
| Asthma |
untyped
GWAS
|
mechanism: SIRT1-Mediated NAD+ Signaling and Protective Deacetylation
|
| Autosomal Dominant Hyper-IgE Syndrome |
untyped
Causative
|
mechanism: STAT3 dominant-negative dysfunction
|
| Coccidioidomycosis |
untyped
Transcription factor for Th17 differentiation; mutations linked to disseminated disease
|
mechanism: Th1/Th17 cell-mediated adaptive immunity
|
| Crohn Disease |
untyped
GWAS
|
mechanism: IL-23/Th17 Axis Dysregulation
|
| Multiple Sclerosis |
untyped
GWAS
|
mechanism: Th1/Th17-Mediated Neuroinflammation
|
| Peripheral T-Cell Lymphoma |
untyped
Copy Number Gain / Pathway Activation
|
scoped to subtype: PTCL-NOS
|
| Psoriasis |
untyped
GWAS
|
mechanism: IL-23/IL-17 Axis
|
| Rheumatoid Arthritis |
untyped
GWAS
|
mechanism: JAK/STAT Signaling
|
| Sezary Syndrome |
untyped
Gain of Function Mutation
|
|
| Systemic Lupus Erythematosus |
untyped
GWAS
|
|
| Ulcerative Colitis |
untyped
GWAS
|
mechanism: Dysregulated Immune Response
|
| AIP-related pituitary adenoma predisposition | no genetic record |
mechanism: IL-6/STAT3 activation in AIP-mutant somatotrophs
|
| Alexander Disease | no genetic record |
mechanism: STAT3-Driven GFAP Upregulation
|
| Atopic Dermatitis | no genetic record |
mechanism: TOPK-STAT3 Signaling Axis
|
| Bacterial meningitis | no genetic record |
mechanism: Blood-Brain Barrier Disruption
|
| Chronic_Obstructive_Pulmonary_Disease | no genetic record |
mechanism: SIRT1-Mediated NAD+ Signaling and Protective Deacetylation
|
| ZNF341 Deficiency | no genetic record |
mechanism: Loss of STAT3 autoinduction in lymphocytes; Reduced basal STAT3 expression
|
An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.
| ClinGen disease | MOI | Classification | dismech entry |
|---|---|---|---|
| hyper-IgE recurrent infection syndrome 1, autosomal dominant MONDO:0007818 | AD | Definitive 2025-06-16 |
|
| STAT3-related early-onset multisystem autoimmune disease MONDO:0014414 | AD | Definitive 2024-05-17 |
no dismech entry |
Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.