STAT1 (Signal Transducer and Activator of Transcription 1)
A critical transcription factor mediating interferon signaling, immune response, and tumor surveillance; mutations cause primary immunodeficiencies and contribute to cancer.
Gene Information Card
| Symbol | STAT1 |
|---|---|
| Full Name | Signal transducer and activator of transcription 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q32.2 |
| NCBI Gene ID | 6772 ncbi.nlm.nih.gov/gene/6772 |
| Ensembl ID | ENSG00000115415 |
| UniProt ID | P42224 |
| OMIM ID | 600555 |
| HGNC ID | 11362 |
| Aliases | ISGF-3, STAT91, CANDF7, IMD31A, IMD31B, IMD31C |
Description
STAT1 encodes a transcription factor that is a key component of the JAK-STAT signaling pathway. It is activated by interferons (IFN-α/β/γ) and other cytokines, leading to its phosphorylation, dimerization, and nuclear translocation to regulate expression of genes involved in immune defense, cell growth, and apoptosis. Mutations in STAT1 cause various primary immunodeficiencies, including susceptibility to mycobacterial and viral infections, and gain-of-function mutations are associated with chronic mucocutaneous candidiasis (CMC). STAT1 also plays a role in tumor suppression and is implicated in cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic mucocutaneous candidiasis (CMC) | Gain-of-function mutations impair IL-17 signaling, leading to defective antifungal immunity. | ClinVar, OMIM (OMIM: 614162) |
| Immunodeficiency 31A (mycobacterial disease) | Loss-of-function mutations impair IFN-γ signaling, causing susceptibility to atypical mycobacteria. | ClinVar, OMIM (OMIM: 614892) |
| Immunodeficiency 31B (viral infections) | Loss-of-function mutations impair IFN-α/β signaling, leading to severe viral infections. | ClinVar, OMIM (OMIM: 613796) |
| Immunodeficiency 31C (combined immunodeficiency) | Complete STAT1 deficiency results in severe combined immunodeficiency. | ClinVar, OMIM (OMIM: 614892) |
| Gastric cancer | Altered STAT1 expression/activity may affect tumor immune surveillance and progression. | COSMIC, PubMed (via NCBI) |
| Head and neck cancer | STAT1 signaling is involved in tumor microenvironment and response to therapy. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | High (nTPM ~ 50-100) | High |
| Spleen | High (nTPM ~ 50-100) | High |
| Lymph node | High (nTPM ~ 50-100) | High |
| Bone marrow | Medium (nTPM ~ 20-50) | Medium |
| Lung | Medium (nTPM ~ 20-50) | Medium |
| Liver | Medium (nTPM ~ 20-50) | Medium |
| Brain | Low (nTPM < 10) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | High (nTPM ~ 100) | Constitutive expression; responsive to IFN |
| HeLa (cervical cancer) | Medium (nTPM ~ 50) | Inducible by IFN |
| A549 (lung carcinoma) | Medium (nTPM ~ 50) | Inducible by IFN |
| MCF7 (breast cancer) | Low (nTPM ~ 20) | Low basal; inducible |
| HepG2 (liver cancer) | Medium (nTPM ~ 50) | Inducible by IFN |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.820C>T (p.Arg274Trp) | Missense (gain-of-function) | Rare (found in CMC patients) | Impaired nuclear export, enhanced STAT1 activity |
| c.1154C>T (p.Thr385Met) | Missense (gain-of-function) | Rare (found in CMC patients) | Enhanced STAT1 phosphorylation and DNA binding |
| c.1757_1758del (p.Lys586fs) | Frameshift (loss-of-function) | Rare (found in immunodeficiency) | Premature stop, loss of function |
| c.1920G>A (p.Met640Ile) | Missense (loss-of-function) | Rare (found in mycobacterial disease) | Impaired IFN-γ signaling |
| c.2113G>A (p.Asp705Asn) | Missense (gain-of-function) | Rare (found in CMC) | Enhanced STAT1 activity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in STAT1 impair IFN-α/β/γ signaling, leading to increased susceptibility to mycobacterial and viral infections. These are typically autosomal recessive or dominant-negative.
Gain of Function (GOF)
Gain-of-function mutations cause hyperactive STAT1 signaling, leading to chronic mucocutaneous candidiasis (CMC) due to defective IL-17 responses. These are autosomal dominant.
Dominant Negative (DN)
Dominant-negative mutations interfere with wild-type STAT1 function, often causing autosomal dominant forms of immunodeficiency (e.g., Immunodeficiency 31B).
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • Signal transducer activity |
| • Protein homodimerization activity | • Protein heterodimerization activity |
| • Interferon-gamma receptor binding | • Cytokine receptor binding |
| • Regulation of transcription by RNA polymerase II | • Innate immune response |
| • Cellular response to interferon-gamma | • Cellular response to interferon-alpha |
| • Apoptotic process | • Cell proliferation |
Pathways
• JAK-STAT signaling pathway
• Interferon alpha/beta signaling
• Interferon gamma signaling
• Cytokine-cytokine receptor interaction
• PD-L1 expression and PD-1 checkpoint pathway in cancer
• Th17 cell differentiation
Protein Summary
STAT1 is a 91 kDa protein that exists as two isoforms (α and β) due to alternative splicing. It contains an N-terminal domain, a coiled-coil domain, a DNA-binding domain, a linker domain, an SH2 domain, and a C-terminal transactivation domain. Upon cytokine stimulation, STAT1 is phosphorylated on tyrosine 701 by JAK kinases, leading to dimerization and nuclear translocation. It binds to gamma-activated sequences (GAS) to regulate gene expression. STAT1 is essential for innate immunity and also has tumor suppressor functions by promoting apoptosis and inhibiting cell cycle progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT1 Knockout HEK293 Cell Line | EDJ-KQ188 | Human | 6772 | Details Get a Quote |
| STAT1 Knockout A-549 Cell Line | EDJ-KQ18897 | Human | 6772 | Details Get a Quote |
| STAT1 Knockout HCT 116 Cell Line | EDJ-KQ18898 | Human | 6772 | Details Get a Quote |
| STAT1 Knockout HeLa Cell Line | EDJ-KQ18899 | Human | 6772 | Details Get a Quote |
| STAT1 Knockout MDCK Cell Line | EDJ-KZ495 | Dog | 488449 | Details Get a Quote |
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