CHEK1

checkpoint kinase 1

Basic information

Region (hg38): 11:125625163-125676255

Links

ENSG00000149554 ∙ NCBI:1111 ∙ OMIM:603078 ∙ HGNC:1925 ∙ Uniprot:O14757 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial ovarian cancer (No Known Disease Relationship), mode of inheritance: AD
• hereditary breast carcinoma (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 21	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Obstetric	33948904; 33953335; 35231158

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHEK1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHEK1 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				23	1	24
missense			24		1	25
nonsense		1	1			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	2	4
Total	0	1	26	24	4

Variants in CHEK1

This is a list of pathogenic ClinVar variants found in the CHEK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-125625767-T-A		CHEK1-related disorder	Uncertain significance (Jan 04, 2024)
11-125625780-A-T		CHEK1-related disorder	Benign (Dec 23, 2019)
11-125625824-G-A		CHEK1-related disorder	Benign (Nov 26, 2019)
11-125625837-A-G		CHEK1-related disorder	Benign (Nov 08, 2019)
11-125625838-C-T		CHEK1-related disorder	Likely benign (May 04, 2022)
11-125625842-T-C		CHEK1-related disorder	Benign (Nov 15, 2019)
11-125625845-A-G		CHEK1-related disorder	Benign (Oct 30, 2019)
11-125625851-C-G		CHEK1-related disorder	Benign (Oct 30, 2019)
11-125625863-C-T		CHEK1-related disorder	Likely benign (Sep 08, 2020)
11-125625873-C-T		CHEK1-related disorder	Uncertain significance (Mar 03, 2023)
11-125625878-G-C		CHEK1-related disorder	Uncertain significance (Jul 09, 2024)
11-125625919-G-T		CHEK1-related disorder	Likely benign (Feb 01, 2023)
11-125625941-G-C		CHEK1-related disorder	Uncertain significance (Jul 18, 2024)
11-125625944-A-T		CHEK1-related disorder	Uncertain significance (Dec 08, 2023)
11-125625950-T-C		CHEK1-related disorder	Uncertain significance (Sep 15, 2022)
11-125625996-G-A		CHEK1-related disorder	Likely benign (Mar 02, 2022)
11-125626807-A-G		CHEK1-related disorder	Uncertain significance (Mar 09, 2024)
11-125626811-C-T		not specified	Likely benign (Feb 17, 2021)
11-125627447-A-G			Benign (Apr 27, 2020)
11-125627626-A-G			Uncertain significance (Mar 03, 2016)
11-125627634-T-C		not specified	Likely benign (May 29, 2021)
11-125627646-C-T		not specified	Likely benign (Sep 21, 2020)
11-125627704-G-A		not specified	Uncertain significance (Apr 05, 2023)
11-125627771-G-T		not specified • CHEK1-related disorder	Uncertain significance (Sep 06, 2022)
11-125627913-T-G		Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHEK1	protein_coding	protein_coding	ENST00000534070	12	51115

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.14e-8	0.926	125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	170	249	0.683	0.0000121	3143
Missense in Polyphen		53	107.08	0.49498		1338
Synonymous	-0.477	89	83.5	1.07	0.00000382	852
Loss of Function	1.83	16	26.1	0.613	0.00000129	337

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000118	0.000118
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000203	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.000198	0.000163
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser- 124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell- cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.
• Pathway: Cell cycle - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Cell Cycle;miRNA Regulation of DNA Damage Response;Retinoblastoma (RB) in Cancer;TP53 Regulates Transcription of DNA Repair Genes;ATR Signaling;ATM Signaling Network in Development and Disease;DNA Damage Response;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Signal Transduction;Gene expression (Transcription);DNA Double-Strand Break Repair;role of brca1 brca2 and atr in cancer susceptibility;cdc25 and chk1 regulatory pathway in response to dna damage;regulation of cell cycle progression by plk3;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Homology Directed Repair;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;RNA Polymerase II Transcription;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;p53-Independent DNA Damage Response;p53-Independent G1/S DNA damage checkpoint;G1/S DNA Damage Checkpoints;G2/M DNA damage checkpoint;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;p73 transcription factor network;cell cycle: g2/m checkpoint;atm signaling pathway;TP53 Regulates Transcription of DNA Repair Genes;Fanconi anemia pathway;rb tumor suppressor/checkpoint signaling in response to dna damage;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling by SCF-KIT;Cell Cycle;Signaling by Receptor Tyrosine Kinases;Circadian rhythm pathway;Processing of DNA double-strand break ends;ATR signaling pathway;p53 pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.527

Intolerance Scores

• loftool: 0.961
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.994
• hipred: Y
• hipred_score: 0.755
• ghis: 0.707

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.830

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chek1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; embryo 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); reproductive 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); neoplasm; pigmentation 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)

Zebrafish Information Network

• Gene name: chek1
• Affected structure: swim bladder
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: DNA damage checkpoint;DNA replication;DNA repair;protein phosphorylation;apoptotic process;cellular response to DNA damage stimulus;DNA damage induced protein phosphorylation;cell cycle;regulation of double-strand break repair via homologous recombination;regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage;peptidyl-threonine phosphorylation;histone H3-T11 phosphorylation;intracellular signal transduction;positive regulation of cell cycle;negative regulation of mitotic nuclear division;regulation of mitotic centrosome separation;chromatin-mediated maintenance of transcription;negative regulation of G0 to G1 transition;cellular response to mechanical stimulus;signal transduction involved in G2 DNA damage checkpoint;replicative senescence;regulation of signal transduction by p53 class mediator;regulation of histone H3-K9 acetylation
• Cellular component: chromosome, telomeric region;chromatin;condensed nuclear chromosome;extracellular space;nucleus;nucleoplasm;cytoplasm;centrosome;cytosol;protein-containing complex;intracellular membrane-bounded organelle
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;kinase activity;protein domain specific binding;histone kinase activity (H3-T11 specific)