CHEK2: Checkpoint Kinase 2 - A Key DNA Damage Response Regulator
Comprehensive gene card, expression, mutations, and clinical significance of CHEK2 in cancer susceptibility
Gene Information Card
| Symbol | CHEK2 |
|---|---|
| Full Name | Checkpoint kinase 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 22q12.1 |
| NCBI Gene ID | 11200 ncbi.nlm.nih.gov/gene/11200 |
| Ensembl ID | ENSG00000183765 |
| UniProt ID | O96017 |
| OMIM ID | 604373 |
| HGNC ID | 16627 |
| Aliases | CDS1, CHK2, RAD53, HuCds1, PP1425 |
Description
CHEK2 (checkpoint kinase 2) is a serine/threonine-protein kinase that plays a critical role in the DNA damage response pathway. It is activated by ATM in response to double-strand breaks and phosphorylates key substrates including p53, BRCA1, and CDC25A, leading to cell cycle arrest, DNA repair, or apoptosis. Germline mutations in CHEK2 are associated with increased risk of breast, prostate, and colorectal cancers, and are implicated in Li-Fraumeni syndrome 2.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss-of-function mutations impair DNA damage checkpoint, leading to genomic instability | ClinVar, COSMIC |
| Li-Fraumeni syndrome 2 | Germline CHEK2 mutations disrupt p53-mediated apoptosis and cell cycle arrest | OMIM #604373 |
| Prostate cancer | CHEK2 variants (e.g., I157T) reduce kinase activity, increasing susceptibility | NCBI Gene, ClinVar |
| Colorectal cancer | CHEK2 truncating mutations (e.g., 1100delC) elevate cancer risk | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 12.5 | Medium |
| Prostate | 8.3 | Low |
| Colon | 15.1 | Medium |
| Lung | 10.2 | Medium |
| Ovary | 9.8 | Low |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 14.2 | Moderate expression |
| PC3 (prostate cancer) | 7.9 | Low expression |
| HCT116 (colorectal cancer) | 16.5 | Moderate expression |
| A549 (lung cancer) | 11.0 | Moderate expression |
| HEK293 (embryonic kidney) | 20.3 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| 1100delC | Frameshift deletion | ~1% in European populations | Loss of function; truncates protein, abolishes kinase activity |
| I157T | Missense | ~5% in European populations | Reduced kinase activity; moderate risk for breast/prostate cancer |
| R145W | Missense | Rare | Loss of function; disrupts ATM-mediated activation |
| S428F | Missense | Rare | Loss of function; impairs substrate phosphorylation |
Mutation functional classification
Loss of Function (LOF)
Most CHEK2 cancer-associated mutations (e.g., 1100delC, I157T, R145W) are loss-of-function, impairing kinase activity or activation, leading to defective DNA damage checkpoint and increased genomic instability.
Gain of Function (GOF)
No well-characterized gain-of-function mutations are reported in CHEK2.
Dominant Negative (DN)
Some missense mutations (e.g., I157T) may exert a dominant-negative effect by dimerizing with wild-type CHEK2 and reducing overall checkpoint function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ATM-mediated DNA damage response (Reactome: R-HSA-5693565)
• p53-dependent G1/S DNA damage checkpoint (Reactome: R-HSA-69580)
• Cell cycle checkpoints (KEGG: hsa04110)
• Apoptosis (KEGG: hsa04210)
Protein Summary
CHEK2 is a 543-amino acid serine/threonine kinase with an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal kinase domain. It is activated by ATM phosphorylation at Thr68 in response to DNA double-strand breaks. Activated CHEK2 phosphorylates multiple substrates including p53 (Ser20), BRCA1 (Ser988), and CDC25A (Ser123), promoting cell cycle arrest, DNA repair, or apoptosis. The protein exists as a monomer in the inactive state and dimerizes upon activation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHEK2 Knockout HEK293 Cell Line | EDJ-KQ7330 | Human | 11200 | Details Get a Quote |
| CHEK2 Knockout A-549 Cell Line | EDJ-KQ32412 | Human | 11200 | Details Get a Quote |
| CHEK2 Knockout HCT 116 Cell Line | EDJ-KQ32413 | Human | 11200 | Details Get a Quote |
| CHEK2 Knockout HeLa Cell Line | EDJ-KQ32414 | Human | 11200 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
