Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659).
Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest.
Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML.
Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1.
Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978).
Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659)
Homodimer. Homodimerization is part of the activation process but the dimer may dissociate following activation. Interacts with PML.
Interacts with TP53. Interacts with RB1; phosphorylates RB1. Interacts with BRCA1.
Interacts (phosphorylated at Thr-68) with MDC1; requires ATM-mediated phosphorylation of CHEK2. Interacts with TP53BP1; modulates CHEK2 phosphorylation at Thr-68 in response to ionizing radiation. Interacts with CDC25A; phosphorylates CDC25A and mediates its degradation in response to ionizing radiation.
Interacts with CUL1; mediates CHEK2 ubiquitination and regulation. Interacts with CDKN2AIP. Interacts (via protein kinase domain) with CCAR2 (via N-terminus).
Interacts with SIRT1
High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues
A disorder characterized by an increased risk for developing various types of benign and/or malignant neoplasms that arise at an accelerated rate and in different organs.
A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
A sarcoma originating in bone-forming cells, affecting the ends of long bones.
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type.
Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
No mutation information available.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CHEK2, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 15
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT06033092 | BRCA Mutation, PALB2 Gene Mutation, Ductal Carcinoma in Situ, Lobular Carcinoma in Situ, ATM Gene Mutation, CHEK2 Gene Mutation, CDH1 Gene Mutation, RAD51C Gene Mutation, RAD51D Gene Mutation | Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT05033756 | Malignant Neoplasm of Breast, Breast Cancer | Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT07499999 | Breast Cancer, Ductal Carcinoma, Estrogen-receptor-positive Breast Cancer, Atypical Lobular Hyperplasia, BRCA2 Mutation, CHEK2 Gene Mutation, Ataxia Telangiectasia Mutated Gene Mutation | Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer | PHASE2 | NOT_YET_RECRUITING |
| NCT02401347 | Advanced Breast Cancer, HER2/Neu Negative, Triple-Negative Breast Cancer | Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors | PHASE2 | COMPLETED |
| NCT03344965 | Metastatic Breast Cancer, Invasive Breast Cancer, Somatic Mutation Breast Cancer (BRCA1), Somatic Mutation Breast Cancer (BRCA2), CHEK2 Gene Mutation, ATM Gene Mutation, PALB2 Gene Mutation, RAD51 Gene Mutation, BRIP1 Gene Mutation, NBN Gene Mutation | Olaparib In Metastatic Breast Cancer | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT03377556 | ATM Gene Mutation, ATR Gene Mutation, BARD1 Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, CHEK1 Gene Mutation, CHEK2 Gene Mutation, FANCA Gene Mutation, FANCC Gene Mutation, FANCD2 Gene Mutation, FANCF Gene Mutation, FANCM Gene Mutation, NBN Gene Mutation, PALB2 Gene Mutation, RAD51 Gene Mutation, RAD51B Gene Mutation, RAD54L Gene Mutation, Recurrent Squamous Cell Lung Carcinoma, RPA1 Gene Mutation, Stage IV Squamous Cell Lung Carcinoma AJCC v7 | Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer | PHASE2 | COMPLETED |
| NCT02952534 | Metastatic Castration Resistant Prostate Cancer | A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency | PHASE2 | COMPLETED |
| NCT05097274 | Prostate Cancer, BRCA Mutation, Mismatch Repair Gene Mutation, ATM Gene Mutation, HOXB13 Germline Mutation, CHEK2 Gene Mutation, PALB2 Gene Mutation | The GENPET Study - An Imaging Study of FCH-PET-CT in Men With Prostate Cancer and a DNA Repair Gene Mutation. | N/A | RECRUITING |
| NCT05420064 | BRCA1 Mutation, POLD1 Gene Mutation, CDKN2A Mutation, BRCA2 Mutation, POLE Gene Mutation, APC Gene Mutation, ATM Gene Mutation, MLH1 Gene Mutation, BARD1 Gene Mutation, MSH2 Gene Mutation, BRIP1 Gene Mutation, MSH6 Gene Mutation, CHEK2 Gene Mutation, PMS2 Gene Mutation, PALB2 Gene Mutation, EPCAM Gene Mutation, RAD51C Gene Mutation, BMPR1A Gene Mutation, RAD51D Gene Mutation, SMAD4, PTEN Gene Mutation, GREM1 | An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results | NA | RECRUITING |
| NCT06177171 | BRCA1 Mutation, BRCA2 Mutation, BRCA Mutation, PALB2 Gene Mutation, Checkpoint Kinase 2 Gene Mutation, ATM Gene Mutation | Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors | PHASE1 | RECRUITING |