HCK Gene – Hematopoietic Cell Kinase | NCBI, UniProt, OMIM, ClinVar

HCK (hematopoietic cell kinase) is a member of the Src family of non-receptor tyrosine kinases. It is predominantly expressed in hematopoietic cells, particularly in myeloid lineages. HCK plays critical roles in cell proliferation, differentiation, phagocytosis, and immune signaling. Dysregulation of HCK has been implicated in chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and other hematologic malignancies. HCK is also involved in inflammatory responses and has been studied as a potential therapeutic target.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG: hsa04664 – Fc epsilon RI signaling pathway

• KEGG: hsa04650 – Natural killer cell mediated cytotoxicity

• KEGG: hsa04666 – Fc gamma R-mediated phagocytosis

• Reactome: R-HSA-2029480 – Fcgamma receptor (FCGR) dependent phagocytosis

• Reactome: R-HSA-1433557 – Signaling by SCF-KIT

HCK encodes a 526-amino acid protein (UniProt P08631) with a molecular weight of approximately 59 kDa. It contains an N-terminal SH4 domain for membrane localization, followed by SH3, SH2, and tyrosine kinase domains. HCK is activated by engagement of various immune receptors (e.g., Fc receptors, integrins) and phosphorylates downstream targets such as STAT5, VAV1, and PI3K. Its activity is tightly regulated by phosphorylation at Tyr411 (activation loop) and Tyr527 (C-terminal inhibitory site).