STAT3 Gene - Signal Transducer and Activator of Transcription 3
A critical transcription factor in cytokine signaling, immunity, and cancer
Gene Information Card
| Symbol | STAT3 |
|---|---|
| Full Name | Signal transducer and activator of transcription 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 6774 ncbi.nlm.nih.gov/gene/6774 |
| Ensembl ID | ENSG00000168610 |
| UniProt ID | P40763 |
| OMIM ID | 102582 |
| HGNC ID | 11364 |
| Aliases | APRF, HIES, ADMIO, MGC17067 |
Description
The STAT3 gene encodes a transcription factor that mediates cellular responses to various cytokines and growth factors. It plays a central role in immune regulation, cell proliferation, differentiation, and survival. STAT3 is activated by phosphorylation via JAK kinases in response to interleukins (e.g., IL-6, IL-10) and growth factors, leading to dimerization, nuclear translocation, and target gene transcription. Dysregulation of STAT3 signaling is implicated in numerous diseases, including immunodeficiencies, autoimmune disorders, and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant hyper-IgE syndrome (Job syndrome) | Loss-of-function mutations in STAT3 impair Th17 cell differentiation and IL-6/IL-10 signaling, leading to recurrent infections, eczema, and skeletal abnormalities. | OMIM #147060; ClinVar |
| Autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) | Gain-of-function mutations or overactivation of STAT3 promote pro-inflammatory cytokine production and T-cell dysregulation. | OMIM #102582; PubMed |
| Various cancers (e.g., breast, lung, colorectal, lymphoma) | Constitutive activation of STAT3 (via phosphorylation) drives oncogenic gene expression, promoting proliferation, survival, angiogenesis, and immune evasion. | COSMIC; PubMed |
| STAT3-related early-onset multisystem autoimmune disease | Gain-of-function mutations in STAT3 cause lymphoproliferation, autoimmune cytopenias, and interstitial lung disease. | OMIM #615952; ClinVar |
| Hepatocellular carcinoma | STAT3 activation in liver cells promotes tumor growth and metastasis through upregulation of anti-apoptotic and proliferative genes. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 20.1 | High |
| Bone marrow | 15.3 | Medium |
| Lung | 12.8 | Medium |
| Spleen | 11.5 | Medium |
| Kidney | 9.2 | Low |
| Brain | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 25.3 | High expression; constitutive activation in CML |
| HeLa (cervical cancer) | 18.7 | Moderate; responsive to IL-6 |
| A549 (lung cancer) | 22.1 | High; associated with oncogenic signaling |
| MCF7 (breast cancer) | 14.5 | Moderate; estrogen receptor positive |
| HepG2 (liver cancer) | 19.8 | High; involved in acute phase response |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R382W | Missense | Rare (germline) | Loss-of-function; associated with hyper-IgE syndrome |
| V637M | Missense | Rare (germline) | Gain-of-function; causes autoimmune disease |
| D661Y | Missense | Somatic (cancer) | Gain-of-function; constitutive activation in various tumors |
| K658N | Missense | Somatic (cancer) | Gain-of-function; promotes oncogenic transcription |
| Y705F | Missense | Somatic (cancer) | Loss of phosphorylation site; dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in STAT3, typically in the DNA-binding or SH2 domains, impair its transcriptional activity, leading to immunodeficiency (e.g., hyper-IgE syndrome) and defective Th17 cell differentiation.
Gain of Function (GOF)
Gain-of-function mutations, often in the SH2 domain or C-terminal region, enhance STAT3 activation and nuclear signaling, resulting in autoimmune disorders and oncogenic transformation.
Dominant Negative (DN)
Dominant-negative mutations produce a STAT3 protein that can dimerize with wild-type STAT3 but lacks transcriptional activity, thereby suppressing normal signaling. These are commonly seen in hyper-IgE syndrome.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Signal transducer activity | • Protein homodimerization activity |
| • Cytokine receptor binding | • Kinase binding |
| • Transcription coregulator binding | • Nucleus |
| • Cytoplasm | • Cellular response to cytokine stimulus |
| • Regulation of cell population proliferation | • Inflammatory response |
| • Immune response |
Pathways
• JAK-STAT signaling pathway
• IL-6 signaling pathway
• IL-10 signaling pathway
• IL-23 signaling pathway
• PD-L1 expression and PD-1 checkpoint pathway in cancer
• Th17 cell differentiation
• Acute phase response
• EGFR tyrosine kinase inhibitor resistance
Protein Summary
STAT3 is a 770-amino acid protein with a molecular weight of ~88 kDa. It contains conserved domains: an N-terminal domain, a coiled-coil domain, a DNA-binding domain, a SH2 domain, and a C-terminal transactivation domain. Upon cytokine stimulation, JAK kinases phosphorylate STAT3 at tyrosine 705, inducing dimerization and nuclear translocation. In the nucleus, STAT3 binds to specific DNA response elements to regulate gene expression. STAT3 also undergoes acetylation and phosphorylation at serine 727, modulating its activity. It interacts with various coactivators and corepressors, influencing a wide range of biological processes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT3 Knockout HEK293 Cell Line | EDJ-KQ903 | Human | 6774 | Details Get a Quote |
| STAT3 Knockout HeLa Cell Line | EDJ-KQ18072 | Human | 6774 | Details Get a Quote |
| STAT3 Knockout A-549 Cell Line | EDJ-KQ21087 | Human | 6774 | Details Get a Quote |
| STAT3 Knockout HCT 116 Cell Line | EDJ-KQ21089 | Human | 6774 | Details Get a Quote |
| Stat3 Knockout CT26.WT Cell Line | EDJ-KZ496 | Mouse | 20848 | Details Get a Quote |
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