STAT1

Chr 2q32.2

signal transducer and activator of transcription 1

Aliases:: STAT91, ISGF-3
MANE:: ENST00000361099.8

OMIM: 600555 ↗NCBI: 6772 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

STAT1 · P42224

v62025-08-01

Predicted Aligned Error matrix for STAT1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

87.3/ 100

Confident

750 residues

Confidence breakdown

Very high(≥ 90)70%
Confident(70–90)17%
Low(50–70)6%
Very low(< 50)7%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Childhood interstitial lung disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
COVID-19 research
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Infantile enterocolitis & monogenic inflammatory bowel disease
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Gastrointestinal epithelial barrier disorders
Diabetes with additional phenotypes suggestive of a monogenic aetiology
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial diabetes
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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Disease associations (Open Targets)

Chronic mucocutaneous candidosis
0.81
immunodeficiency 31B
0.78
autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
0.75
Susceptibility to viral and mycobacterial infections
0.61
cancer
0.55
Autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome
0.51
immunodeficiency disease
0.48
combined immunodeficiency
0.47
severe combined immunodeficiency
0.47
infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development
0.44

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Signal transducer and activator of transcription 1-alpha/beta

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754, PubMed:32814877). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity)