STAT4 Gene: Signal Transducer and Activator of Transcription 4
A key transcription factor in immune regulation, implicated in autoimmune diseases and cancer.
Gene Information Card
| Symbol | STAT4 |
|---|---|
| Full Name | Signal transducer and activator of transcription 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q32.2-q32.3 |
| NCBI Gene ID | 6775 ncbi.nlm.nih.gov/gene/6775 |
| Ensembl ID | ENSG00000138378 |
| UniProt ID | Q14765 |
| OMIM ID | 600558 |
| HGNC ID | 11365 |
| Aliases | SLEB11; MGC129684; MGC129685 |
Description
The STAT4 gene encodes a member of the signal transducer and activator of transcription (STAT) family of transcription factors. STAT4 is critical for mediating responses to interleukin-12 (IL-12) and interleukin-23 (IL-23), driving T-helper 1 (Th1) and Th17 differentiation, respectively. It plays a central role in immune regulation, and genetic variants in STAT4 are associated with susceptibility to several autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Additionally, altered STAT4 expression or activity has been implicated in cancer progression and immune evasion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | Risk allele (e.g., rs7574865) increases STAT4 expression, enhancing Th1/Th17 responses and autoantibody production. | Multiple GWAS and meta-analyses (e.g., OMIM, ClinVar) |
| Systemic Lupus Erythematosus | Same risk allele contributes to altered STAT4 signaling, promoting inflammatory cytokine production. | OMIM, ClinVar |
| Sjögren's Syndrome | STAT4 risk variants are associated with increased susceptibility, likely via enhanced type I interferon responses. | OMIM, ClinVar |
| Inflammatory Bowel Disease (Crohn's disease) | STAT4 variants may modulate IL-12/IL-23 signaling, affecting mucosal immunity. | ClinVar, literature |
| Cancer (e.g., breast, gastric) | Aberrant STAT4 expression or activation can promote tumor growth and metastasis, possibly through immune modulation. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 20.1 | High |
| Spleen | 18.5 | High |
| Bone marrow | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Liver | 4.2 | Low |
| Brain | 1.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression |
| K-562 (leukemia) | 10.8 | Medium expression |
| HeLa (cervical) | 3.4 | Low expression |
| A549 (lung) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7574865 (intronic) | SNP | ~25% in Europeans | Risk allele for autoimmune diseases; increases STAT4 expression |
| rs7582694 (intronic) | SNP | ~20% in East Asians | Associated with SLE and RA |
| p.Arg7Trp (missense) | Missense | Rare | Potential functional impact; not well characterized |
| p.Val90Met (missense) | Missense | Rare | Reported in cancer; functional significance unknown |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in STAT4 are rare and not well documented; likely lead to impaired Th1/Th17 responses and increased susceptibility to infections.
Gain of Function (GOF)
Gain-of-function mutations or overexpression can enhance STAT4 signaling, leading to excessive inflammation and autoimmunity.
Dominant Negative (DN)
Dominant-negative mutations have not been clearly identified for STAT4; however, altered splicing or truncations could potentially exert dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Protein homodimerization activity | • Signal transducer activity |
| • Cytokine receptor binding | • Nucleus |
| • Cytoplasm |
Pathways
• IL-12 signaling pathway
• IL-23 signaling pathway
• Th1 and Th17 cell differentiation
• JAK-STAT signaling pathway
• Cytokine-cytokine receptor interaction
Protein Summary
STAT4 is a 748-amino-acid protein with a molecular weight of ~86 kDa. It contains an N-terminal domain, a coiled-coil domain, a DNA-binding domain, an SH2 domain, and a C-terminal transactivation domain. Upon IL-12 or IL-23 stimulation, STAT4 is phosphorylated by JAK kinases, leading to dimerization and nuclear translocation, where it regulates transcription of target genes involved in immune responses. STAT4 is predominantly expressed in immune cells, especially T cells, natural killer cells, and dendritic cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT4 Knockout HEK293 Cell Line | EDJ-KQ536 | Human | 6775 | Details Get a Quote |
| STAT4 Knockout HCT 116 Cell Line | EDJ-KQ18021 | Human | 6775 | Details Get a Quote |
| STAT4 Knockout A-549 Cell Line | EDJ-KQ18903 | Human | 6775 | Details Get a Quote |
| STAT4 Knockout HeLa Cell Line | EDJ-KQ54582 | Human | 6775 | Details Get a Quote |
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