HCST (Hematopoietic Cell Signal Transducer)
DAP10, a key signaling adaptor in NK and T cell activation
Gene Information Card
| Symbol | HCST |
|---|---|
| Full Name | Hematopoietic cell signal transducer |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 10870 ncbi.nlm.nih.gov/gene/10870 |
| Ensembl ID | ENSG00000126264 |
| UniProt ID | Q9UBK5 |
| OMIM ID | 604089 |
| HGNC ID | 4858 |
| Aliases | DAP10, KAP10, PIK3AP |
Description
HCST encodes DAP10, a transmembrane signaling adaptor protein that associates with NKG2D (KLRK1) to form an activating receptor complex on natural killer (NK) cells and some T cells. DAP10 contains a YxxM motif in its cytoplasmic tail that recruits PI3K and GRB2, mediating cell activation, cytotoxicity, and cytokine production. HCST is essential for NK cell-mediated immune surveillance and has been implicated in cancer, autoimmune diseases, and viral infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency (NK cell deficiency) | Loss-of-function mutations in HCST impair NKG2D signaling, leading to defective NK cell cytotoxicity and increased susceptibility to viral infections. | ClinVar, OMIM |
| Celiac disease | HCST polymorphisms may alter NKG2D-mediated activation of intraepithelial lymphocytes, contributing to intestinal inflammation. | NCBI Gene, literature |
| Cancer (various) | HCST expression is dysregulated in tumors; loss of DAP10 reduces NKG2D-mediated tumor cell killing, facilitating immune evasion. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lung | 8.3 | Low |
| Bone marrow | 7.1 | Low |
| Small intestine | 6.9 | Low |
| Whole blood | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 | 15.2 | High expression in NK cell line |
| Jurkat | 2.1 | Low expression in T cell line |
| K-562 | 1.8 | Low expression in erythroleukemia line |
| HEK293 | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.95G>A (p.Arg32Gln) | Missense | <0.01% | Alters transmembrane domain, may impair NKG2D binding |
| c.236C>T (p.Pro79Leu) | Missense | <0.01% | Located in cytoplasmic tail, potential effect on signaling |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt DAP10 expression or NKG2D association lead to impaired NK cell activation and increased infection risk.
Gain of Function (GOF)
Not reported in HCST; gain-of-function is not a known mechanism for this gene.
Dominant Negative (DN)
No dominant-negative mutations have been described for HCST.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NKG2D signaling in NK cells (Reactome: R-HSA-2424491)
• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome: R-HSA-198933)
• PI3K/AKT activation (via YxxM motif)
Protein Summary
DAP10 (HCST) is a 93-amino-acid transmembrane adaptor protein with a short extracellular domain, a transmembrane region, and a cytoplasmic tail containing a YxxM motif. It forms a disulfide-linked homodimer that non-covalently associates with NKG2D. Upon ligand binding, the YxxM motif is phosphorylated, recruiting PI3K and GRB2, leading to activation of downstream pathways including AKT and MAPK. DAP10 is critical for NK cell cytotoxicity, cytokine production, and T cell co-stimulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCST Knockout HEK293 Cell Line | EDJ-KQ7194 | Human | 10870 | Details Get a Quote |
| HCST Knockout HeLa Cell Line | EDJ-KQ55505 | Human | 10870 | Details Get a Quote |
| HCST Knockout A-549 Cell Line | EDJ-KQ63994 | Human | 10870 | Details Get a Quote |
| HCST Knockout HCT 116 Cell Line | EDJ-KQ72445 | Human | 10870 | Details Get a Quote |
