HCST

hematopoietic cell signal transducer

Basic information

Region (hg38): 19:35902529-35904377

Previous symbols: [ "PIK3AP" ]

Links

ENSG00000126264

∙ NCBI:10870 ∙ OMIM:604089 ∙ HGNC:16977 ∙ Uniprot:Q9UBK5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HCST gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCST gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			3 clinvar			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1 clinvar	1
Total	0	0	3	0	1

Variants in HCST

This is a list of pathogenic ClinVar variants found in the HCST region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
19-35902613-T-A	not specified	Uncertain significance (Dec 11, 2023)	3104544
19-35902628-T-C	not specified	Uncertain significance (Jun 02, 2024)	3283668
19-35903786-T-C	not specified	Uncertain significance (Jun 27, 2022)	2351270
19-35903787-G-A	not specified	Uncertain significance (Mar 06, 2023)	2493928
19-35904357-A-AC		Benign (Jan 07, 2020)	1238245

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCST	protein_coding	protein_coding	ENST00000246551	4	1898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00205	0.522	125731	0	11	125742	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.483	43	52.9	0.813	0.00000231	567
Missense in Polyphen		10	10.349	0.96624		109
Synonymous	1.03	17	23.3	0.728	0.00000103	215
Loss of Function	0.165	4	4.37	0.915	1.86e-7	53

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000431	0.000431
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000657	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transmembrane adapter protein which associates with KLRK1 to form an activation receptor KLRK1-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full KLRK1-HCST-mediated activation and ultimate killing of target cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity and enhances cytokine production initiated via DAP12/TYROBP-associated receptors. In T-cells, it provides primarily costimulation for TCR-induced signals. KLRK1-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells; indeed, melanoma cells that do not express KLRK1 ligands escape from immune surveillance mediated by NK cells. {ECO:0000269|PubMed:10426994, ECO:0000269|PubMed:10528161, ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:11777960, ECO:0000269|PubMed:12740575, ECO:0000269|PubMed:12740576, ECO:0000269|PubMed:16002667, ECO:0000269|PubMed:16339517, ECO:0000269|PubMed:16582911, ECO:0000269|PubMed:18097042}.;
Pathway: Natural killer cell mediated cytotoxicity - Homo sapiens (human);Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System (Consensus)

Recessive Scores

pRec: 0.192

Intolerance Scores

loftool: 0.515
rvis_EVS: 0.64
rvis_percentile_EVS: 83.63

Haploinsufficiency Scores

pHI: 0.242
hipred: N
hipred_score: 0.180
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.659

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Hcst
Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; immune system phenotype; skeleton phenotype;

Gene ontology

Biological process: protein phosphorylation;positive regulation of phosphatidylinositol 3-kinase signaling;regulation of immune response
Cellular component: plasma membrane;cell surface;integral component of membrane
Molecular function: signaling receptor binding;protein binding;phosphatidylinositol 3-kinase binding