SOCS4 Gene - Suppressor of Cytokine Signaling 4 | Function, Mutations & Disease

SOCS4 encodes a member of the suppressor of cytokine signaling (SOCS) family, which are negative regulators of cytokine receptor signaling via the JAK/STAT pathway. The protein contains a central SH2 domain and a C-terminal SOCS box, mediating interaction with phosphorylated tyrosine residues and targeting signaling proteins for ubiquitination. SOCS4 is involved in immune regulation, growth factor signaling, and has been implicated in cancer and inflammatory diseases.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• JAK-STAT signaling pathway (KEGG: hsa04630)

• Cytokine-cytokine receptor interaction (KEGG: hsa04060)

• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)

SOCS4 is a 440-amino acid protein (UniProt Q8WXH5) with a central SH2 domain that binds phosphotyrosine motifs on activated cytokine receptors and JAK kinases, and a C-terminal SOCS box that recruits E3 ubiquitin ligase components to target bound proteins for proteasomal degradation. It negatively regulates signaling by cytokines such as IL-6, EGF, and growth hormone. SOCS4 is widely expressed in immune tissues and is frequently downregulated in cancers, where its loss contributes to persistent STAT3 activation and tumor progression.