{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gebbia M"],"funding":["NHLBI NIH HHS","NHGRI NIH HHS"],"pagination":["2675-2692"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11639082"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["111(12)"],"pubmed_abstract":["The tumor suppressor CHEK2 encodes the serine/threonine protein kinase CHK2 which, upon DNA damage, is important for pausing the cell cycle, initiating DNA repair, and inducing apoptosis. CHK2 phosphorylation of the tumor suppressor BRCA1 is also important for mitotic spindle assembly and chromosomal stability. Consistent with its cell-cycle checkpoint role, both germline and somatic variants in CHEK2 have been linked to breast and other cancers. Over 90% of clinical germline CHEK2 missense variants are classified as variants of uncertain significance, complicating diagnosis of CHK2-dependent cancer. We therefore sought to test the functional impact of all possible missense variants in CHK2. Using a scalable multiplexed assay based on the ability of human CHK2 to complement DNA sensitivity"],"journal":["American journal of human genetics"],"pubmed_title":["A missense variant effect map for the human tumor-suppressor protein CHK2."],"pmcid":["PMC11639082"],"funding_grant_id":["R01 HL164675","RM1 HG010461"],"pubmed_authors":["Roth FP","Kishore N","Reuter J","Gavac M","Hamilton R","Jiang R","Li R","Boonen RA","van Attikum H","Nguyen M","Weile J","Wahl A","Fowler DM","Zimmerman D","Sun S","Johnson B","Gebbia M","Dines JN","Couch FJ"],"additional_accession":[]},"is_claimable":false,"name":"A missense variant effect map for the human tumor-suppressor protein CHK2.","description":"The tumor suppressor CHEK2 encodes the serine/threonine protein kinase CHK2 which, upon DNA damage, is important for pausing the cell cycle, initiating DNA repair, and inducing apoptosis. CHK2 phosphorylation of the tumor suppressor BRCA1 is also important for mitotic spindle assembly and chromosomal stability. Consistent with its cell-cycle checkpoint role, both germline and somatic variants in CHEK2 have been linked to breast and other cancers. Over 90% of clinical germline CHEK2 missense variants are classified as variants of uncertain significance, complicating diagnosis of CHK2-dependent cancer. We therefore sought to test the functional impact of all possible missense variants in CHK2. Using a scalable multiplexed assay based on the ability of human CHK2 to complement DNA sensitivity","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-03T03:08:49.694Z","creation":"2025-04-04T01:54:40.749Z"},"accession":"S-EPMC11639082","cross_references":{"pubmed":["39642869"],"doi":["10.1016/j.ajhg.2024.10.013"]}}