AlphaFold predicted structure
STAT4 · Q14765
Mean pLDDT
86.3/ 100
Confident
748 residues
Confidence breakdown
- Very high(≥ 90)63%
- Confident(70–90)23%
- Low(50–70)8%
- Very low(< 50)6%
Open interactive 3D viewer
AlphaFold (Jumper et al., 2021) · CC BY 4.0
STAT4
Chr 2q32.2-q32.3signal transducer and activator of transcription 4
- MANE:
- ENST00000392320.7
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Primary immunodeficiency or monogenic inflammatory bowel disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedCOVID-19 research
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disease associations (Open Targets)
disabling pansclerotic morphea of childhood
0.62rheumatoid arthritis
0.59systemic lupus erythematosus
0.57hypothyroidism
0.49ACPA-positive rheumatoid arthritis
0.44systemic sclerosis
0.43myxedema
0.41thyroid gland disorder
0.41primary biliary cholangitis
0.40autoimmune disease
0.40
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Signal transducer and activator of transcription 4
Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response (PubMed:10961885, PubMed:37256972, PubMed:8943379). Plays a key role in the differentiation of T-helper 1 cells and the production of interferon-gamma (PubMed:12213961, PubMed:35614130). Also participates in multiple neutrophil functions including chemotaxis and production of the neutrophil extracellular traps (By similarity). After IL12 binding to its receptor IL12RB2, STAT4 interacts with the intracellular domain of IL12RB2 and becomes tyrosine phosphorylated (PubMed:10415122, PubMed:7638186). Phosphorylated STAT4 then homodimerizes and migrates to the nucleus where it can recognize STAT target sequences present in IL12 responsive genes. Although IL12 appears to be the predominant activating signal, STAT4 can also be phosphorylated and activated in response to IFN-gamma stimulation via JAK1 and TYK2 and in response to different interleukins including IL23, IL2 and IL35 (PubMed:11114383, PubMed:34508746). Transcription activation of IFN-gamma gene is mediated by interaction with JUN that forms a complex that efficiently interacts with the AP-1-related sequence of the IFN-gamma promoter (By similarity). In response to IFN-alpha/beta signaling, acts as a transcriptional repressor and suppresses IL5 and IL13 mRNA expression during response to T-cell receptor (TCR) activation (PubMed:26990433)
Diseases associated with STAT4
Curated MONDO disease pages that list STAT4 among their top associated genes.