CSK Gene: C-Terminal Src Kinase - Function, Mutations, and Disease Associations

The CSK gene encodes C-terminal Src kinase, a cytoplasmic tyrosine kinase that negatively regulates Src family kinases (SFKs) by phosphorylating their C-terminal inhibitory tyrosine residue. CSK plays a critical role in controlling cell proliferation, adhesion, migration, and immune receptor signaling. Dysregulation of CSK is implicated in various cancers and immune disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Regulation of Src family kinases (Reactome: R-HSA-8848021)

• Signaling by Src-family kinases (Reactome: R-HSA-177929)

• T-cell receptor signaling pathway (KEGG: hsa04660)

• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)

CSK is a 50 kDa cytoplasmic tyrosine kinase composed of an N-terminal SH2 domain, a central SH3 domain, and a C-terminal kinase domain. It specifically phosphorylates the C-terminal tyrosine (Tyr530 in Src) of Src family kinases, inducing an intramolecular inhibitory conformation. CSK is ubiquitously expressed but enriched in hematopoietic tissues. Its activity is essential for maintaining low basal SFK activity and regulating immune receptor signaling.