Checkpoint Kinase 2

Alternative Names

  • CHEK2
  • Checkpoint Kinase 2, S. pombe, Homolog of
  • CHK2
  • RAD53, S. Cerevisiae, Homolog of
  • RAD53
  • CDS1, S. Pombe, Homolog of

Associated Diseases

Breast Cancer
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OMIM Number

604373

NCBI Gene ID

11200

Uniprot ID

O96017

Length

54,680 bases

No. of Exons

22

No. of isoforms

13

Protein Name

Serine/threonine-protein kinase Chk2

Molecular Mass

60915 Da

Amino Acid Count

543

Genomic Location

chr22:28,687,743-28,742,422

Gene Map Locus
22q12.1

Description

In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [From RefSeq]

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_007194.4:c.470T>CLebanonchr22:28725099Likely Pathogenic, Pathogenic, Risk factorUncertain SignificanceBreast CancerNG_008150.2:g.21768T>C; NM_007194.4:c.470T>C; NP_009125.1:p.Ile157Thr178799615591

Other Reports

United Arab Emirates

In a retrospective study of breast cancer patients in the UAE, Altinoz et al (2020) identified three Emirati patients with pathogenic variants in the CHEK2 gene. An additional two Emiratis were found to have variants of uncertain significance in the same gene.  

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