CHEK1
Chr 11ADcheckpoint kinase 1
Also known as: CHK1, OZEMA21
This serine/threonine kinase regulates cell cycle checkpoints and DNA damage repair by phosphorylating key substrates including CDC25 phosphatases, TP53, and RAD51. Mutations cause oocyte/zygote/embryo maturation arrest 21, an autosomal dominant condition affecting early reproductive development. The gene is highly intolerant to loss-of-function mutations (pLI near 0, LOEUF 0.931), suggesting that complete protein loss is likely incompatible with normal development.
Primary Disease Associations & Inheritance
No known disease relationship
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
202 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 3 | 60 | 0 | 64 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 1 | 63 | 12 | 1 | 77 |
Likely Benign | 1 | 1 | 11 | 25 | 38 |
Benign | 0 | 1 | 8 | 1 | 10 |
| Total | 3 | 68 | 94 | 27 | 192 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CHEK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Moving Foward With Myeloma (MFM)
NOT YET RECRUITINGStudy of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers
ACTIVE NOT RECRUITINGA Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
RECRUITINGNiraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects
ACTIVE NOT RECRUITINGStudy of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations
RECRUITINGExternal Resources
Links to major genomics databases and tools