STAT6 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the STAT6 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | STAT6 |
|---|---|
| Full Name | Signal transducer and activator of transcription 6 |
| Gene Type | Protein-coding |
| Chromosomal Location | 12q13.3 |
| NCBI Gene ID | 6778 ncbi.nlm.nih.gov/gene/6778 |
| Ensembl ID | ENSG00000166888 |
| UniProt ID | P42226 |
| OMIM ID | 601512 |
| HGNC ID | 11368 |
| Aliases | D12S1644, IL-4-STAT, STAT6B, STAT6C |
Description
The STAT6 gene encodes a member of the signal transducer and activator of transcription (STAT) family of transcription factors. STAT6 plays a critical role in mediating cellular responses to interleukin-4 (IL-4) and interleukin-13 (IL-13), key cytokines in the regulation of immune responses, particularly in T-helper type 2 (Th2) cell differentiation, immunoglobulin class switching, and allergic inflammation. Upon cytokine stimulation, STAT6 is phosphorylated by Janus kinases (JAKs), leading to its dimerization, nuclear translocation, and activation of target gene transcription. Dysregulation of STAT6 signaling is implicated in various diseases, including asthma, allergic conditions, and certain cancers, particularly lymphomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Asthma | STAT6 mediates IL-4/IL-13 signaling, promoting Th2 inflammation, airway hyperresponsiveness, and mucus production. Genetic variants in STAT6 are associated with asthma susceptibility. | ClinVar, OMIM |
| Atopic dermatitis | Enhanced STAT6 activation contributes to Th2-driven skin inflammation and impaired skin barrier function. | OMIM, PubMed |
| Lymphoma (e.g., follicular lymphoma, Hodgkin lymphoma) | Somatic mutations in STAT6, particularly in the DNA-binding domain, lead to constitutive activation and oncogenic signaling, promoting tumor cell survival and proliferation. | COSMIC, PubMed |
| Immunodeficiency (rare) | Loss-of-function mutations in STAT6 cause an autosomal recessive primary immunodeficiency characterized by impaired IL-4/IL-13 signaling, leading to recurrent infections and elevated IgE levels. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Lymph node | 12.3 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.5 | Low |
| Lung | 6.2 | Low |
| Skin | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| Ramos (B lymphocyte) | 15.2 | High expression; relevant to immune function |
| THP-1 (monocyte) | 10.4 | Moderate expression |
| A549 (lung carcinoma) | 4.3 | Low expression |
| MCF7 (breast carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.Gln358His (rs324011) | SNP | Common (MAF ~0.3) | Associated with asthma susceptibility; may alter STAT6 function |
| p.Arg358Gln (rs3024974) | SNP | Common (MAF ~0.2) | Associated with atopic dermatitis; potential effect on DNA binding |
| p.Asn417Tyr | Somatic missense | Rare in lymphomas | Gain-of-function; constitutive activation |
| p.Arg418Cys | Somatic missense | Rare in lymphomas | Gain-of-function; constitutive activation |
| p.Arg418His | Somatic missense | Rare in lymphomas | Gain-of-function; constitutive activation |
| p.Val547Met | Germline missense | Very rare | Loss-of-function; associated with immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in STAT6 impair IL-4/IL-13 signaling, leading to defective Th2 differentiation and immunoglobulin class switching. This results in primary immunodeficiency with recurrent infections and elevated IgE levels.
Gain of Function (GOF)
Gain-of-function mutations, typically somatic in lymphomas, cause constitutive STAT6 activation, leading to uncontrolled cell proliferation and survival. These mutations often occur in the DNA-binding domain, enhancing transcriptional activity.
Dominant Negative (DN)
Dominant-negative mutations are rare but can occur, producing a STAT6 protein that interferes with wild-type function, thereby reducing IL-4/IL-13 responsiveness.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein dimerization activity | • signal transducer activity |
| • regulation of transcription by RNA polymerase II | • cytokine-mediated signaling pathway |
| • cell differentiation | • inflammatory response |
| • immune response |
Pathways
• IL-4 signaling pathway
• IL-13 signaling pathway
• Th1 and Th2 cell differentiation
• JAK-STAT signaling pathway
• Allograft rejection signaling
• Role of cytokines in mediating communication between immune cells
Protein Summary
STAT6 is a 847-amino acid protein with a molecular weight of approximately 94 kDa. It contains an N-terminal domain, a coiled-coil domain, a DNA-binding domain, a SH2 domain, and a C-terminal transactivation domain. Upon IL-4/IL-13 stimulation, STAT6 is phosphorylated at tyrosine 641 by JAK kinases, leading to dimerization via SH2 domain interactions. The dimer translocates to the nucleus and binds to specific DNA response elements to regulate gene expression. STAT6 is essential for Th2 cell differentiation, IgE class switching, and expression of cell surface markers such as CD23 and MHC class II. Its activity is negatively regulated by phosphatases, SOCS proteins, and PIAS proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT6 Knockout HEK293 Cell Line | EDJ-KQ248 | Human | 6778 | Details Get a Quote |
| STAT6 Knockout HeLa Cell Line | EDJ-KQ18024 | Human | 6778 | Details Get a Quote |
| STAT6 Knockout A-549 Cell Line | EDJ-KQ18909 | Human | 6778 | Details Get a Quote |
| STAT6 Knockout HCT 116 Cell Line | EDJ-KQ18910 | Human | 6778 | Details Get a Quote |
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