CSK

C-terminal Src kinase, the group of SH2 domain containing|Csk family tyrosine kinases

Basic information

Region (hg38): 15:74782079-74803197

Links

ENSG00000103653 ∙ NCBI:1445 ∙ OMIM:124095 ∙ HGNC:2444 ∙ Uniprot:P41240 ∙ 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 CSK gene.

• Inborn genetic diseases (4 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSK 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			4		1	5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	1	1

Variants in CSK

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

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

Position	Type	Phenotype	Significance	ClinVar
15-74798663-G-A		not specified	Uncertain significance (Jan 19, 2024)
15-74798834-C-G		not specified	Uncertain significance (Feb 13, 2024)
15-74798889-G-A		not specified	Uncertain significance (Jan 24, 2024)
15-74799293-A-C			Likely benign (Oct 01, 2022)
15-74799310-G-A		not specified	Uncertain significance (Jan 02, 2024)
15-74799325-C-T		not specified	Uncertain significance (Jun 07, 2023)
15-74799396-G-A		not specified	Uncertain significance (Nov 10, 2022)
15-74801568-G-A			Benign (Jun 12, 2018)
15-74801841-C-T		not specified	Uncertain significance (Dec 13, 2022)
15-74802368-A-G		not specified	Uncertain significance (Jun 11, 2021)
15-74802442-G-A			Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSK	protein_coding	protein_coding	ENST00000220003	12	21142

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000234	124652	0	1	124653	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.98	103	295	0.349	0.0000193	2914
Missense in Polyphen		34	156.76	0.2169		1542
Synonymous	0.168	124	126	0.981	0.00000917	877
Loss of Function	4.76	1	28.3	0.0353	0.00000163	293

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T- cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK. {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:9281320}.
• Pathway: Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);VEGF Signaling Pathway;Integrin-mediated Cell Adhesion;Integrated Lung Cancer Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;MAP2K and MAPK activation;Disease;Signal Transduction;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;integrin signaling pathway;vegf hypoxia and angiogenesis;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;Phosphorylation of CD3 and TCR zeta chains;TCR signaling;PD-1 signaling;Costimulation by the CD28 family;Integrin alphaIIb beta3 signaling;Immune System;Adaptive Immune System;Signaling by EGFR;Platelet Aggregation (Plug Formation);cell to cell adhesion signaling;Platelet activation, signaling and aggregation;IL-7 signaling;EGFR1;Integrin signaling;CXCR4-mediated signaling events;Hemostasis;GAB1 signalosome;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;BCR signaling pathway;JAK STAT pathway and regulation;EPO signaling;Signaling by Receptor Tyrosine Kinases;Signaling by RAS mutants;VEGF;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;TCR signaling in naïve CD8+ T cells;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.671

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.691
• hipred: Y
• hipred_score: 0.831
• ghis: 0.477

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Csk
• Phenotype: respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; 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); 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); normal phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; immune system phenotype; cellular phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: csk
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: adaptive immune response;protein phosphorylation;brain development;negative regulation of cell population proliferation;negative regulation of low-density lipoprotein particle clearance;peptidyl-tyrosine phosphorylation;T cell costimulation;negative regulation of interleukin-6 production;negative regulation of kinase activity;adherens junction organization;negative regulation of Golgi to plasma membrane protein transport;positive regulation of MAP kinase activity;negative regulation of bone resorption;protein autophosphorylation;oligodendrocyte differentiation;negative regulation of phagocytosis;T cell receptor signaling pathway;regulation of Fc receptor mediated stimulatory signaling pathway;negative regulation of ERK1 and ERK2 cascade;cellular response to peptide hormone stimulus
• Cellular component: cytoplasm;cytosol;plasma membrane;cell-cell junction;membrane raft;extracellular exosome
• Molecular function: protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;protein binding;ATP binding;protein C-terminus binding;kinase activity;protein phosphatase binding;protein kinase A catalytic subunit binding;identical protein binding;metal ion binding;proline-rich region binding