CISH: Cytokine Inducible SH2 Containing Protein
A negative regulator of cytokine signaling with roles in immune regulation and cancer susceptibility.
Gene Information Card
| Symbol | CISH |
|---|---|
| Full Name | Cytokine Inducible SH2 Containing Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 1154 ncbi.nlm.nih.gov/gene/1154 |
| Ensembl ID | ENSG00000114737 |
| UniProt ID | Q9NSE2 |
| OMIM ID | 602441 |
| HGNC ID | 1984 |
| Aliases | SOCS, CIS, CIS-1, G18 |
Description
The CISH gene encodes a member of the suppressor of cytokine signaling (SOCS) family. This protein contains an SH2 domain and a SOCS box domain. It functions as a negative regulator of cytokine signaling by binding to phosphorylated tyrosine residues on cytokine receptors and inhibiting JAK-STAT signaling pathways. CISH is induced by various cytokines, including IL-2, IL-3, IL-6, and erythropoietin, and plays a critical role in immune homeostasis, T-cell development, and growth hormone signaling. Polymorphisms in CISH have been associated with susceptibility to infectious diseases and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Infectious disease susceptibility (e.g., malaria, tuberculosis, bacteremia) | CISH polymorphisms reduce expression, impairing negative regulation of cytokine signaling, leading to altered immune responses. | Association studies in human populations (NCBI, OMIM) |
| Hepatocellular carcinoma | CISH overexpression may promote tumor growth by modulating JAK-STAT signaling and immune evasion. | Expression studies and clinical correlations (COSMIC, NCBI) |
| Breast cancer | CISH copy number alterations and expression changes affect cytokine signaling and cell proliferation. | Genomic profiling studies (COSMIC, ClinVar) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Medium |
| Lung | 4.1 | Low |
| Liver | 3.5 | Low |
| Kidney | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HEK 293 (embryonic kidney) | 6.7 | Moderate expression |
| HeLa (cervical cancer) | 4.2 | Low expression |
| A549 (lung carcinoma) | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.292C>T (p.Arg98Trp) | Missense | Rare | Potential loss of function; altered SH2 domain binding |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression |
| c.292+1G>A | Splice donor | Rare | Splicing defect; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the SH2 domain or SOCS box, or cause premature truncation, impair the ability of CISH to bind phosphorylated receptors and inhibit JAK-STAT signaling, leading to enhanced cytokine responses.
Gain of Function (GOF)
Not well documented; overexpression of wild-type CISH can suppress cytokine signaling, but specific gain-of-function mutations are not reported.
Dominant Negative (DN)
Mutations that produce a truncated protein lacking the SOCS box may interfere with wild-type CISH function by competing for receptor binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• JAK-STAT signaling pathway (KEGG: hsa04630)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• SOCS-mediated negative regulation of cytokine signaling (Reactome: R-HSA-913531)
Protein Summary
CISH (Cytokine Inducible SH2 Containing Protein) is a 257-amino acid protein with a molecular weight of approximately 29 kDa. It contains an N-terminal SH2 domain that binds to phosphotyrosine residues on activated cytokine receptors (e.g., IL-2 receptor beta chain, erythropoietin receptor, growth hormone receptor) and a C-terminal SOCS box that mediates interaction with the ubiquitin-proteasome system, targeting bound signaling proteins for degradation. By inhibiting JAK-STAT signaling, CISH acts as a key negative feedback regulator of cytokine responses, controlling T-cell activation, proliferation, and differentiation. Its expression is rapidly induced by cytokines, ensuring tight regulation of immune and inflammatory responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CISH Knockout HEK293 Cell Line | EDJ-KQ451 | Human | 1154 | Details Get a Quote |
| CISH Knockout HCT 116 Cell Line | EDJ-KQ18758 | Human | 1154 | Details Get a Quote |
| CISH Knockout HeLa Cell Line | EDJ-KQ18759 | Human | 1154 | Details Get a Quote |
| CISH Knockout A-549 Cell Line | EDJ-KQ61379 | Human | 1154 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
