SOCS1 Gene - Suppressor of Cytokine Signaling 1
A key negative regulator of JAK-STAT signaling, implicated in immune regulation, inflammation, and cancer.
Gene Information Card
| Symbol | SOCS1 |
|---|---|
| Full Name | Suppressor of Cytokine Signaling 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.13 |
| NCBI Gene ID | 8651 ncbi.nlm.nih.gov/gene/8651 |
| Ensembl ID | ENSG00000185338 |
| UniProt ID | O15524 |
| OMIM ID | 603597 |
| HGNC ID | 16839 |
| Aliases | CISH1, SSI1, JAB, TIP3 |
Description
The SOCS1 gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS1 is a key negative regulator of cytokine signaling, particularly the JAK-STAT pathway. It inhibits cytokine receptor signaling by directly binding to JAK kinases and promoting their degradation via ubiquitination. SOCS1 is involved in immune regulation, inflammation, and tumor suppression. Its expression is induced by various cytokines, and it plays a critical role in maintaining immune homeostasis and preventing excessive inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Loss of SOCS1 expression leads to sustained JAK-STAT activation, promoting cell proliferation and survival. | Frequent promoter methylation and reduced expression observed in HCC (COSMIC, ClinVar). |
| Chronic myeloid leukemia | SOCS1 downregulation contributes to constitutive JAK-STAT signaling, enhancing leukemic cell growth. | Reduced SOCS1 expression in CML patients (COSMIC). |
| Autoimmune diseases (e.g., systemic lupus erythematosus) | SOCS1 deficiency leads to hyperactivation of immune cells and increased cytokine signaling, contributing to autoimmunity. | Genetic variants and altered expression reported in autoimmune cohorts (ClinVar). |
| Infectious diseases (e.g., viral hepatitis) | SOCS1 modulates antiviral immune responses; dysregulation can affect viral clearance and inflammation. | Expression changes observed in infected tissues (NCBI Gene). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | High | High expression in immune tissues |
| Spleen | High | High expression in immune tissues |
| Bone marrow | Medium | Moderate expression |
| Thymus | Medium | Moderate expression |
| Liver | Low | Low expression |
| Kidney | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Low | Cervical cancer cell line |
| K562 | Medium | Chronic myeloid leukemia cell line |
| A549 | Low | Lung carcinoma cell line |
| MCF7 | Low | Breast cancer cell line |
| Jurkat | High | T cell leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of function, reduced protein expression |
| c.214C>T (p.Arg72Trp) | Missense | Rare | Impaired JAK binding, loss of inhibitory function |
| c.331G>A (p.Asp111Asn) | Missense | Rare | Altered SOCS box function, reduced ubiquitination activity |
| Promoter methylation | Epigenetic | Common in cancer | Silencing of SOCS1 expression, leading to constitutive JAK-STAT signaling |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair SOCS1's ability to bind JAKs or promote their degradation, leading to hyperactive cytokine signaling. Examples include missense mutations in the SH2 domain or SOCS box.
Gain of Function (GOF)
Rare; not well documented. Potential gain-of-function mutations could enhance SOCS1 activity, leading to excessive suppression of cytokine signaling, but such variants are not commonly reported.
Dominant Negative (DN)
Mutations that produce a truncated or altered protein that can interfere with wild-type SOCS1 function, often seen in the SOCS box region, leading to loss of negative regulation.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004860 - protein kinase inhibitor activity | • GO:0005515 - protein binding |
| • GO:0005737 - cytoplasm | • GO:0005829 - cytosol |
| • GO:0007259 - JAK-STAT cascade | • GO:0009968 - negative regulation of signal transduction |
| • GO:0010629 - negative regulation of gene expression | • GO:0035556 - intracellular signal transduction |
| • GO:0042325 - regulation of phosphorylation | • GO:0043123 - positive regulation of I-kappaB kinase/NF-kappaB signaling |
Pathways
• JAK-STAT signaling pathway
• Cytokine-cytokine receptor interaction
• Toll-like receptor signaling pathway
• T cell receptor signaling pathway
• PD-L1 expression and PD-1 checkpoint pathway in cancer
Protein Summary
SOCS1 is a small protein (~24 kDa) containing a central SH2 domain and a C-terminal SOCS box. It functions as a negative feedback regulator of cytokine signaling. Upon cytokine stimulation, SOCS1 is rapidly induced and binds to JAK kinases via its SH2 domain, inhibiting their catalytic activity. The SOCS box recruits the elongin B/C complex, leading to ubiquitination and proteasomal degradation of JAKs. SOCS1 also regulates other signaling pathways, including NF-kB and TLR signaling. Its expression is tightly controlled, and dysregulation contributes to inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SOCS1 Knockout HEK293 Cell Line | EDJ-KQ14661 | Human | 8651 | Details Get a Quote |
| SOCS1 Knockout BEAS-2B Cell Line | EDJ-KZ486 | Human | 8651 | Details Get a Quote |
| SOCS1 Knockout HeLa Cell Line | EDJ-KQ54971 | Human | 8651 | Details Get a Quote |
| SOCS1 Knockout A-549 Cell Line | EDJ-KQ63453 | Human | 8651 | Details Get a Quote |
| SOCS1 Knockout HCT 116 Cell Line | EDJ-KQ71921 | Human | 8651 | Details Get a Quote |
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