STAT2 Gene - Signal Transducer and Activator of Transcription 2
Key mediator of type I and III interferon signaling, associated with immunodeficiency and viral susceptibility
Gene Information Card
| Symbol | STAT2 |
|---|---|
| Full Name | Signal transducer and activator of transcription 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.2 |
| NCBI Gene ID | 6773 ncbi.nlm.nih.gov/gene/6773 |
| Ensembl ID | ENSG00000170581 |
| UniProt ID | P52630 |
| OMIM ID | 600556 |
| HGNC ID | 11363 |
| Aliases | ISGF-3, P113, STAT113 |
Description
STAT2 (Signal Transducer and Activator of Transcription 2) is a critical transcription factor that mediates cellular responses to type I (IFN-α/β) and type III (IFN-λ) interferons. Upon interferon binding to their receptors, STAT2 is phosphorylated by JAK kinases, forms a complex with STAT1 and IRF9 (ISGF3), and translocates to the nucleus to induce expression of interferon-stimulated genes (ISGs) that establish an antiviral state. STAT2 is unique among STAT family members as it lacks a canonical SH2 domain and is essential for antiviral immunity. Mutations in STAT2 can lead to primary immunodeficiency with increased susceptibility to viral infections, particularly to measles virus and other RNA viruses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 44 | Loss-of-function mutations impair ISGF3 formation, leading to defective type I/III interferon signaling and increased susceptibility to viral infections. | OMIM #616636; ClinVar |
| Severe viral infections (e.g., measles, influenza) | STAT2 deficiency disrupts antiviral response, allowing uncontrolled viral replication. | Case reports in ClinVar and literature |
| Susceptibility to viral infections in general | Impaired ISG induction due to STAT2 dysfunction. | OMIM and functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.4 | Medium |
| Spleen | 11.8 | Medium |
| Liver | 10.2 | Medium |
| Kidney | 9.5 | Low |
| Brain | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| A549 | 14.8 | High expression |
| HepG2 | 12.1 | Medium |
| K562 | 8.7 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1836C>T (p.Arg612Ter) | Nonsense | Rare | Loss of function; truncated protein lacking transactivation domain |
| c.1759G>A (p.Glu587Lys) | Missense | Rare | Impaired STAT2 phosphorylation and ISGF3 formation |
| c.1381C>T (p.Arg461Cys) | Missense | Rare | Reduced DNA binding activity |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations are loss-of-function, leading to defective interferon signaling and increased viral susceptibility.
Gain of Function (GOF)
No gain-of-function mutations have been clinically characterized for STAT2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type STAT2 function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein heterodimerization activity | • signal transducer activity |
| • interferon-gamma receptor binding | • nucleus |
| • cytoplasm | • ISGF3 complex |
Pathways
• JAK-STAT signaling pathway
• Type I interferon signaling pathway
• Type III interferon signaling pathway
• Innate immune response
Protein Summary
STAT2 is a 113 kDa protein composed of 851 amino acids. It contains an N-terminal domain, a coiled-coil domain, a DNA-binding domain, a linker domain, and a transactivation domain, but lacks a canonical SH2 domain. STAT2 is primarily cytoplasmic in unstimulated cells. Upon type I or III interferon stimulation, it is phosphorylated on tyrosine 690 by JAK1/TYK2, leading to heterodimerization with STAT1 and association with IRF9 to form the ISGF3 complex. ISGF3 translocates to the nucleus and binds to interferon-stimulated response elements (ISREs) to drive transcription of ISGs. STAT2 also has non-canonical functions in DNA damage response and innate immunity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT2 Knockout HEK293 Cell Line | EDJ-KQ535 | Human | 6773 | Details Get a Quote |
| STAT2 Knockout A-549 Cell Line | EDJ-KQ18900 | Human | 6773 | Details Get a Quote |
| STAT2 Knockout HCT 116 Cell Line | EDJ-KQ18901 | Human | 6773 | Details Get a Quote |
| STAT2 Knockout HeLa Cell Line | EDC90521 | Human | 6773 | Details Get a Quote |
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