HCK

HCK proto-oncogene, Src family tyrosine kinase, the group of Src family tyrosine kinases|SH2 domain containing

Basic information

Region (hg38): 20:32052197-32101856

Links

ENSG00000101336 ∙ NCBI:3055 ∙ OMIM:142370 ∙ HGNC:4840 ∙ Uniprot:P08631 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoinflammation with pulmonary and cutaneous vasculitis (Limited), mode of inheritance: Unknown
• autoinflammation with pulmonary and cutaneous vasculitis (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammation with pulmonary and cutaneous vasculitis	AD	Allergy/Immunology/Infectious	Individuals may be at risk of infections, and awareness may allow preventative measures and early and aggressive treatment of infections; The condition can involve systemic autoinflammation, and medical management (eg, with JAK inhibitors) has been described as providing some benefit	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Pulmonary	34536415

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCK 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					1	1
missense			41	6		47
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	1	41	7	1

Variants in HCK

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

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

Position	Type	Phenotype	Significance	ClinVar
20-32052425-C-T		not specified	Likely benign (Apr 16, 2024)
20-32052427-G-T		HCK-related condition	Uncertain significance (Aug 13, 2024)
20-32052437-T-A			Likely benign (May 01, 2024)
20-32052437-T-C		not specified	Uncertain significance (Jan 18, 2023)
20-32052455-G-A		not specified	Uncertain significance (Sep 27, 2021)
20-32054284-A-G		HCK-related condition	Uncertain significance (Sep 09, 2024)
20-32071696-G-A		not specified	Likely benign (Jun 05, 2024)
20-32071700-G-T		not specified	Uncertain significance (Dec 21, 2022)
20-32071774-A-C		not specified	Uncertain significance (Jun 17, 2024)
20-32071775-T-G		not specified	Uncertain significance (Sep 17, 2021)
20-32071781-C-T		not specified	Uncertain significance (Oct 22, 2021)
20-32073327-T-C			Benign (Jul 01, 2024)
20-32073335-A-G		not specified	Uncertain significance (Oct 29, 2024)
20-32073347-C-A		not specified	Uncertain significance (Dec 03, 2024)
20-32073358-G-C		not specified	Uncertain significance (Feb 21, 2025)
20-32073373-C-T		not specified	Likely benign (Mar 03, 2025)
20-32073757-G-A		not specified	Uncertain significance (Apr 25, 2023)
20-32073763-A-G		not specified	Uncertain significance (Dec 14, 2023)
20-32073771-C-G		not specified	Uncertain significance (Nov 10, 2022)
20-32074623-A-G			Likely benign (Feb 01, 2025)
20-32074630-G-C		not specified	Uncertain significance (Oct 16, 2024)
20-32074646-G-A		not specified	Uncertain significance (Aug 02, 2021)
20-32074696-C-T		not specified	Uncertain significance (Nov 17, 2022)
20-32074708-C-G		not specified	Uncertain significance (Dec 03, 2024)
20-32079797-G-A		not specified	Uncertain significance (Aug 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCK	protein_coding	protein_coding	ENST00000375852	13	49669

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0198	0.980	125718	0	29	125747	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.70	236	322	0.733	0.0000198	3455
Missense in Polyphen		81	149.77	0.54085		1582
Synonymous	1.49	106	127	0.832	0.00000843	1000
Loss of Function	3.64	9	30.8	0.292	0.00000181	327

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000306	0.000304
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790, ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024, ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982, ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996, ECO:0000269|PubMed:9407116}.
• Disease: DISEASE: Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.; DISEASE: Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;IL-3 Signaling Pathway;Focal Adhesion;IL-6 signaling pathway;Chemokine signaling pathway;Microglia Pathogen Phagocytosis Pathway;Disease;Signaling by Interleukins;hiv-1 defeats host-mediated resistance by cem15;Cytokine Signaling in Immune system;Host Interactions of HIV factors;HIV Infection;Infectious disease;Immune System;KitReceptor;BCR;roles of arrestin dependent recruitment of src kinases in gpcr signaling;Nef and signal transduction;CXCR4-mediated signaling events;Thromboxane A2 receptor signaling;The role of Nef in HIV-1 replication and disease pathogenesis;Ephrin B reverse signaling;Class I PI3K signaling events;IL5;IL6;Glypican 1 network;IL8- and CXCR1-mediated signaling events;amb2 Integrin signaling;Regulation of p38-alpha and p38-beta;Alpha-synuclein signaling;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;IL6-mediated signaling events;IL8- and CXCR2-mediated signaling events;EPHA forward signaling;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.532

Intolerance Scores

• loftool: 0.176
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.09

Haploinsufficiency Scores

• pHI: 0.642
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hck
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; neoplasm; 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype

Gene ontology

• Biological process: leukocyte migration involved in immune response;innate immune response-activating signal transduction;protein phosphorylation;inflammatory response;cell adhesion;transmembrane receptor protein tyrosine kinase signaling pathway;integrin-mediated signaling pathway;mesoderm development;positive regulation of cell population proliferation;regulation of cell shape;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;cell differentiation;positive regulation of actin filament polymerization;lipopolysaccharide-mediated signaling pathway;peptidyl-tyrosine autophosphorylation;Fc-gamma receptor signaling pathway involved in phagocytosis;negative regulation of apoptotic process;leukocyte degranulation;respiratory burst after phagocytosis;protein autophosphorylation;regulation of defense response to virus by virus;regulation of inflammatory response;regulation of phagocytosis;regulation of DNA-binding transcription factor activity;interferon-gamma-mediated signaling pathway;regulation of podosome assembly;positive regulation of actin cytoskeleton reorganization
• Cellular component: nucleoplasm;lysosome;Golgi apparatus;cytosol;actin filament;plasma membrane;caveola;focal adhesion;transport vesicle;extrinsic component of cytoplasmic side of plasma membrane;cell projection
• Molecular function: phosphotyrosine residue binding;protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;signaling receptor binding;protein binding;ATP binding