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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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CHEK1
checkpoint kinase 1
Chromosome 11 Β· 11q24.2
NCBI Gene: 1111Ensembl: ENSG00000149554.15HGNC: HGNC:1925UniProt: B4DT73
616PubMed Papers
21Diseases
9Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHub GeneKinase
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
GO:0005615condensed nuclear chromosomeprotein serine/threonine kinase activityprotein bindingneurodegenerative diseaseoocyte/zygote/embryo maturation arrest 21alopecia areataMale infertility due to gonadal dysgenesis or sperm disorder
✦AI Summary

CHEK1 (checkpoint kinase 1) is a serine/threonine protein kinase that serves as a critical component of the DNA damage response and cell cycle checkpoint pathways. The protein functions primarily within the ATR-CHEK1 signaling cascade, which is activated by single-stranded DNA and serves as the principal direct effector of DNA damage and replication checkpoints, making it essential for cell survival 1. CHEK1 mediates cellular responses to DNA damage by regulating the S to G2/M phase transition and maintaining genomic stability through phosphorylation of downstream targets including CEP170 2. The kinase plays important roles in DNA repair processes, particularly in regulating double-strand break repair via homologous recombination 1. CHEK1 expression is significantly elevated in multiple cancer types, including multiple myeloma, lung adenocarcinoma, and thyroid cancer, where high expression correlates with poor clinical outcomes, advanced disease stages, and reduced survival 345. In multiple myeloma, CHEK1 promotes chr11 instability, drug resistance, and bone lesion formation by activating osteoclast differentiation 2. The protein's essential role in checkpoint signaling and its overexpression in cancers make it an attractive therapeutic target, with inhibition showing synergistic effects when combined with other DNA damage response pathway inhibitors 6.

Sources cited
1
CHEK1 is part of the ATR-CHEK1 pathway activated by single-stranded DNA and is essential for DNA damage and replication checkpoints
PMID: 21034966
2
CHEK1 expression is increased in multiple myeloma patients and correlates with poor clinical outcomes
PMID: 32894664
3
CHEK1 promotes chromosomal instability, drug resistance, and bone lesion formation in multiple myeloma through CEP170 phosphorylation
PMID: 34090465
4
CHEK1 is overexpressed in lung adenocarcinoma and serves as a potential prognostic biomarker
PMID: 34882011
5
CHEK1 is a molecular target in thyroid cancer treatment
PMID: 39808342
6
CHEK1 inhibition shows synergistic effects with other DNA damage response pathway inhibitors
PMID: 37898670
Disease Associationsβ“˜21
neurodegenerative diseaseOpen Targets
0.54Moderate
oocyte/zygote/embryo maturation arrest 21Open Targets
0.48Moderate
alopecia areataOpen Targets
0.28Weak
Male infertility due to gonadal dysgenesis or sperm disorderOpen Targets
0.27Weak
hereditary neoplastic syndromeOpen Targets
0.15Weak
Inherited cancer-predisposing syndromeOpen Targets
0.15Weak
neoplasmOpen Targets
0.13Weak
cancerOpen Targets
0.13Weak
non-small cell lung carcinomaOpen Targets
0.13Weak
small cell lung carcinomaOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.11Weak
ovarian cancerOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
lymphomaOpen Targets
0.11Weak
Miyoshi myopathyOpen Targets
0.10Weak
acute myeloid leukemiaOpen Targets
0.10Weak
melanomaOpen Targets
0.10Weak
glioblastoma multiformeOpen Targets
0.10Suggestive
Oocyte/zygote/embryo maturation arrest 21UniProt
Pathogenic Variants5
NM_001114122.3(CHEK1):c.1036C>T (p.Gln346Ter)Likely pathogenic
not provided|Male infertility due to gonadal dysgenesis or sperm disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 346
NM_001114122.3(CHEK1):c.1136G>A (p.Arg379Gln)Pathogenic
Oocyte/zygote/embryo maturation arrest 21
β˜†β˜†β˜†β˜†2023β†’ Residue 379
NM_001114122.3(CHEK1):c.1324del (p.Arg442fs)Pathogenic
Oocyte/zygote/embryo maturation arrest 21
β˜†β˜†β˜†β˜†2023β†’ Residue 442
NM_001114122.3(CHEK1):c.1325G>A (p.Arg442Gln)Pathogenic
Oocyte/zygote/embryo maturation arrest 21
β˜†β˜†β˜†β˜†2023β†’ Residue 442
NM_001114122.3(CHEK1):c.1259G>A (p.Arg420Lys)Pathogenic
Oocyte/zygote/embryo maturation arrest 21
β˜†β˜†β˜†β˜†2023β†’ Residue 420
View on ClinVar β†—
Drug Targets9
AZD-7762Phase I
Serine/threonine-protein kinase Chk1 inhibitor
PF-00477736Phase I
Serine/threonine-protein kinase Chk1 inhibitor
PREXASERTIBPhase II
Serine/threonine-protein kinase Chk1 inhibitor
ovarian cancer
RABUSERTIBPhase II
Serine/threonine-protein kinase Chk1 inhibitor
Malignant Pancreatic Neoplasm
RG-7602Phase I
Serine/threonine-protein kinase Chk1 inhibitor
lymphoma
RG-7741Phase I
Serine/threonine-protein kinase Chk1 inhibitor
lymphoma
SCH-900776Phase II
Serine/threonine-protein kinase Chk1 inhibitor
UCN-01Phase II
3-phosphoinositide dependent protein kinase-1 inhibitor
non-small cell lung carcinoma
XL-844Phase I
Serine/threonine-protein kinase Chk2 inhibitor
Related Genes
MCM4Protein interaction100%CCNA2Protein interaction100%MCM7Protein interaction100%MCM3Protein interaction100%MCM6Protein interaction100%CDT1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
31%
Ovary
8%
Lung
5%
Liver
5%
Heart
4%
Gene Interaction Network
Click a node to explore
CHEK1MCM4CCNA2MCM7MCM3MCM6CDT1
PROTEIN STRUCTURE
Preparing viewer…
PDB2YEX Β· 1.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.83LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.59 [0.43–0.83]
RankingsWhere CHEK1 stands among ~20K protein-coding genes
  • #376of 20,598
    Most Researched616 Β· top 5%
  • #3,461of 5,498
    Most Pathogenic Variants5
  • #7,091of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedCHEK1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer.
PMID: 21034966
Adv Cancer Res Β· 2010
1.00
2
Strong Correlation between the Expression of CHEK1 and Clinicopathological Features of Patients with Multiple Myeloma.
PMID: 32894664
Crit Rev Eukaryot Gene Expr Β· 2020
0.90
3
Integrative analysis of patient-derived tumoroids and ex vivo organoid modelling of ARID1A loss in bladder cancer reveals therapeutic molecular targets.
PMID: 39892702
Cancer Lett Β· 2025
0.86
4
FOXM1 Promotes Non-Small Cell Lung Cancer Progression by Increasing CHEK1 Expression.
PMID: 40434671
Curr Med Sci Β· 2025
0.82
5
Associations of ATR and CHEK1 single nucleotide polymorphisms with breast cancer.
PMID: 23844225
PLoS One Β· 2013
0.80