CHEK2

CHEK2

<div class="infobox infobox-gene">
<span class="infobox-title">CHEK2</span>
<table>
<tr><th>Full Name</th><td>Checkpoint Kinase 2</td></tr>
<tr><th>Chromosomal Location</th><td>22q12.1</td></tr>
<tr><th>NCBI Gene ID</th><td>1111</td></tr>
<tr><th>OMIM</th><td>604373</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000149554</td></tr>
<tr><th>UniProt ID</th><td>O96017</td></tr>
<tr><th>Protein</th><td>CHEK2 protein</td></tr>
<tr><th>Associated Diseases</th><td>Li-Fraumeni syndrome variant, Prostate cancer, Breast cancer, Osteosarcoma, Glioma</td></tr>
</table>
</div>

Overview

CHEK2

<div class="infobox infobox-gene">
<span class="infobox-title">CHEK2</span>
<table>
<tr><th>Full Name</th><td>Checkpoint Kinase 2</td></tr>
<tr><th>Chromosomal Location</th><td>22q12.1</td></tr>
<tr><th>NCBI Gene ID</th><td>1111</td></tr>
<tr><th>OMIM</th><td>604373</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000149554</td></tr>
<tr><th>UniProt ID</th><td>O96017</td></tr>
<tr><th>Protein</th><td>CHEK2 protein</td></tr>
<tr><th>Associated Diseases</th><td>Li-Fraumeni syndrome variant, Prostate cancer, Breast cancer, Osteosarcoma, Glioma</td></tr>
</table>
</div>

Overview

Checkpoint kinase 2 (CHEK2) is a serine/threonine-protein kinase encoded by the CHEK2 gene located on chromosome 22q12.1[@ahn2000]. CHEK2 plays a critical role in maintaining genomic stability through its involvement in the DNA damage checkpoint pathway. As a key effector of ATM-mediated DNA damage response, CHEK2 helps coordinate cell cycle arrest, DNA repair, and [apoptosis](/entities/apoptosis) in response to genotoxic stress["@matsuoka2000"].

Mutations in CHEK2 have been associated with increased cancer risk, particularly in the context of Li-Fraumeni-like syndromes. The protein's kinase activity is regulated by phosphorylation in response to DNA double-strand breaks, making it a potential therapeutic target in cancers with defective DNA repair mechanisms.

Function

Function

Checkpoint kinase 2 (CHEK2) is a serine/threonine-protein kinase that plays a critical role in the DNA damage checkpoint pathway[@ahn2000]. In response to DNA double-strand breaks (DSBs), ATM kinase phosphorylates CHEK2 at Thr68, activating its kinase activity[@matsuoka2000]. Activated CHEK2 then phosphorylates multiple downstream targets including:

• p53 (TP53): Phosphorylation at Ser20 disrupts MDM2-mediated degradation, stabilizing p53 and promoting DNA repair or apoptosis[@chehab2000]
• CDC25A/B/C: Phosphorylation leads to cell cycle arrest at G1/S and G2/M checkpoints[@zhou2004]
• BRCA1: Phosphorylation supports homologous recombination repair[@zhang2003]
• E2F1: Phosphorylation regulates transcription of pro-apoptotic genes[@stevens2003]

Disease Associations

Cancer

• Li-Fraumeni syndrome: Heterozygous germline CHEK2*1100delC variant increases cancer risk 2-4 fold[@weischer2008]
• Prostate cancer: CHEK2 variants associated with aggressive disease[@seppala2003]
• Breast cancer: CHEK2 I157T variant increases risk 1.5-2 fold[@bane2007]

Neurodegeneration

• Alzheimer's disease: CHEK2 dysregulation reported in AD brain tissue; involved in neuronal DNA damage response[@hashimoto2002]
• [Parkinson's disease](/diseases/parkinsons-disease): CHEK2 phosphorylation patterns altered in PD models[@jhaveri2013]
• Amyotrophic lateral sclerosis (ALS): CHEK2 activation observed in ALS patient spinal cord[@sathasivam2014]

Expression

CHEK2 is ubiquitously expressed in human tissues with highest levels in testis, thymus, and prostate[@us]. In the brain, CHEK2 is expressed in:

• [Neurons](/entities/neurons) (cortical, hippocampal, cerebellar)[@inoue2002]
• [Astrocytes](/entities/astrocytes)
• [Microglia](/cell-types/microglia-neuroinflammation)
• [Oligodendrocytes](/cell-types/oligodendrocytes)

Therapeutic Implications

• CHEK2 inhibitors: Preclinical compounds in development for cancer therapy[@antoni2007]
• DNA damage response modulators: Combination strategies with radiotherapy or chemotherapy[@zhou2014]

See Also

• [ATM](/genes/atm) - ATM kinase, upstream activator of CHEK2
• [p53](/mechanisms/p53-pathway) - Tumor suppressor, downstream target
• [DNA Damage Response](/mechanisms/dna-damage-response) - Broader pathway context
• [BRCA1](/genes/brca1) - DNA repair partner
• [Alzheimer's Disease](/diseases/alzheimers-disease) - Disease association

External Links

• [NCBI Gene: CHEK2](https://www.ncbi.nlm.nih.gov/gene/1111)
• [UniProt: O96017](https://www.uniprot.org/uniprot/O96017)
• [OMIM: 604373](https://www.omim.org/entry/604373)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CHEK2 discovered through SciDEX knowledge graph analysis: