STAT1

signal transducer and activator of transcription 1

4 disorders 1 causative 1 susceptibility 1 untyped 1 no genetic record 2q32.2 gene with protein product

HGNC:11362 Monarch NCBI Gene 6772 ENSG00000115415 UniProt P42224 OMIM 600555

Aliases: STAT91, ISGF-3.

Normal function · from ai-gene-review (P42224, commit 79fe13b38970) · AI-generated, not KB evidence

STAT1 is a latent cytoplasmic transcription factor that serves as a central mediator of cytokine signaling, particularly interferon responses. Upon cytokine stimulation, STAT1 becomes phosphorylated on Y701 by JAK kinases, forms homodimers or heterodimers (e.g., with STAT2), and translocates to the nucleus where it binds specific DNA elements to regulate gene expression. STAT1 is essential for antiviral and antimicrobial immunity, mediating both type I (IFN-α/β, forming ISGF3 complex) and type II (IFN-γ, forming GAF complex) interferon responses. Knockout studies demonstrate STAT1's non-redundant role in host defense against viruses, bacteria, and fungi.

Master transcriptional regulator of interferon responses and cytokine signaling

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: cellular response to cytokine stimulus; type I interferon-mediated signaling pathway; type II interferon-mediated signaling pathway; innate immune response · locations: nucleus; cytoplasm

SH2 domain-mediated homodimerization and heterodimerization essential for transcriptional activation

molecular function: protein homodimerization activity · directly involved in: positive regulation of receptor signaling pathway via JAK-STAT · locations: nucleus

Sequence-specific DNA binding to interferon-responsive regulatory elements (GAS and ISRE)

molecular function: RNA polymerase II cis-regulatory region sequence-specific DNA binding · directly involved in: positive regulation of transcription by RNA polymerase II · locations: nucleus

In the knowledge base · computed from kb/ at build time

Disorders

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
Chronic Mucocutaneous Candidiasis	causative germline	mechanism: Broad STAT1-Driven Immune Dysregulation; STAT1 Hyperactivation from Impaired Nuclear Dephosphorylation subtype: STAT1 GOF scoped to subtype: STAT1 GOF
Invasive Non-Typhoidal Salmonellosis	susceptibility
Monkeypox	untyped Downregulated during infection
ZNF341 Deficiency	no genetic record	mechanism: Reduced STAT1 expression

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

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
immunodeficiency 31B MONDO:0013427	AR	Definitive 2024-10-06	no dismech entry
autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome MONDO:0013599	AD	Definitive 2024-12-17	Chronic Mucocutaneous Candidiasis causative
Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency MONDO:0013956	AD	Definitive 2024-11-20	no dismech entry

Mechanism modules · computed from kb/

jak_stat_pathway_activation via Chronic Mucocutaneous Candidiasis named in the module itself

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.