SOCS3 Gene: Suppressor of Cytokine Signaling 3
A key negative regulator of JAK/STAT signaling with implications in inflammation, cancer, and metabolic disorders.
Gene Information Card
| Symbol | SOCS3 |
|---|---|
| Full Name | Suppressor of cytokine signaling 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 9021 ncbi.nlm.nih.gov/gene/9021 |
| Ensembl ID | ENSG00000184557 |
| UniProt ID | O14543 |
| OMIM ID | 604176 |
| HGNC ID | 19391 |
| Aliases | CIS3, SSI-3, ATOD4 |
Description
The SOCS3 gene encodes suppressor of cytokine signaling 3, a member of the suppressor of cytokine signaling (SOCS) family. SOCS3 is a key negative regulator of cytokine signaling, particularly the JAK/STAT pathway. It inhibits signal transduction by binding to JAK kinases and cytokine receptors, thereby modulating immune responses, inflammation, and cell growth. SOCS3 expression is induced by various cytokines and growth factors, forming a negative feedback loop. Dysregulation of SOCS3 is implicated in inflammatory diseases, autoimmune disorders, and several cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | Reduced SOCS3 expression leads to enhanced JAK/STAT signaling and increased inflammatory cytokine production. | PMID: 21750548 |
| Inflammatory Bowel Disease | SOCS3 deficiency in intestinal epithelial cells promotes inflammation and colitis-associated tumorigenesis. | PMID: 24503132 |
| Hepatocellular Carcinoma | Hypermethylation of SOCS3 promoter leads to silencing, resulting in constitutive JAK/STAT activation and tumor progression. | PMID: 12835555 |
| Type 2 Diabetes | SOCS3 impairs insulin signaling by promoting ubiquitin-mediated degradation of IRS-1 and IRS-2. | PMID: 15124017 |
| Asthma | SOCS3 overexpression in airway epithelium suppresses Th2 responses, while deficiency exacerbates allergic inflammation. | PMID: 20037587 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Bone Marrow | 8.3 | Low |
| Spleen | 7.9 | Low |
| Lung | 6.4 | Low |
| Adipose Tissue | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical carcinoma; moderate expression |
| HepG2 | 12.8 | Hepatocellular carcinoma; moderate expression |
| A549 | 9.5 | Lung carcinoma; low expression |
| MCF7 | 7.3 | Breast carcinoma; low expression |
| K562 | 5.1 | Chronic myelogenous leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.136C>T (p.Arg46Trp) | Missense | Rare (<0.01%) | Impairs SOCS3 function, leading to enhanced JAK/STAT signaling |
| c.313G>A (p.Val105Met) | Missense | Rare (<0.01%) | Alters protein stability and reduces inhibitory activity |
| c.452_453del (p.Leu151fs) | Frameshift | Not reported | Loss of function; truncated protein |
| Promoter hypermethylation | Epigenetic | Common in cancers | Silences SOCS3 expression, leading to constitutive STAT activation |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish SOCS3's ability to inhibit JAK/STAT signaling, leading to hyperactivation of cytokine pathways.
Gain of Function (GOF)
Rare; not well documented. Overexpression of SOCS3 can suppress anti-tumor immunity.
Dominant Negative (DN)
Some missense mutations may interfere with wild-type SOCS3 function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004860 - protein kinase inhibitor activity | • GO:0005515 - protein binding |
| • GO:0007259 - JAK-STAT cascade | • GO:0009968 - negative regulation of signal transduction |
| • GO:0046426 - negative regulation of JAK-STAT cascade | • GO:0005737 - cytoplasm |
| • GO:0005829 - cytosol |
Pathways
• JAK/STAT signaling pathway
• Cytokine-cytokine receptor interaction
• IL-6 signaling pathway
• Growth hormone signaling
• Leptin signaling pathway
Protein Summary
SOCS3 is a 225-amino acid protein containing a central SH2 domain and a C-terminal SOCS box. It binds to JAK kinases and cytokine receptors, inhibiting their activity and promoting proteasomal degradation. SOCS3 is induced by cytokines such as IL-6, IL-10, and IFN-γ, forming a negative feedback loop. It plays a critical role in regulating immune responses, hematopoiesis, and metabolism. Aberrant SOCS3 expression or function is linked to inflammatory diseases, metabolic disorders, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SOCS3 Knockout HEK293 Cell Line | EDJ-KQ527 | Human | 9021 | Details Get a Quote |
| SOCS3 Knockout A-549 Cell Line | EDJ-KQ18869 | Human | 9021 | Details Get a Quote |
| SOCS3 Knockout HCT 116 Cell Line | EDJ-KQ18870 | Human | 9021 | Details Get a Quote |
| SOCS3 Knockout HeLa Cell Line | EDJ-KQ18871 | Human | 9021 | Details Get a Quote |
| SOCS3 Knockout BEAS-2B Cell Line | EDJ-KZ487 | Human | 9021 | Details Get a Quote |
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