CHEK2 Gene

Name	checkpoint kinase 2
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. [provided by RefSeq, Apr 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHEK2 (Chk2) is a serine‐threonine protein kinase that plays a central role in the cellular response to DNA damage. In cells that acquire persistent double‐strand breaks, CHEK2 functions not only in enforcing cell cycle checkpoints by phosphorylating key downstream effectors such as p53 and BRCA1 but also in mediating non–cell autonomous signals—for example, by facilitating the secretion of inflammatory cytokines from damaged, senescent cells, thereby alerting the tissue microenvironment to genomic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Germline loss‐of‐function mutations, such as the truncating CHEK21100delC variant, compromise its kinase activity and have been associated with a moderate increase in breast cancer risk and predisposition to other cancer types, underscoring its function as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Collectively, these findings illustrate that CHEK2 integrates signals from upstream DNA damage sensors (such as ATM) to coordinate cell cycle arrest, promote DNA repair processes, and maintain genomic stability, all of which are critical for suppressing tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francis Rodier, Jean-Philippe Coppé, Christopher K Patil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1909"}], "href": "https://doi.org/10.1038/ncb1909"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19597488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19597488"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hanne Meijers-Heijboer, Ans van den Ouweland, Jan Klijn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low-penetrance susceptibility to breast cancer due to CHEK2()1100delC in noncarriers of BRCA1 or BRCA2 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng879"}], "href": "https://doi.org/10.1038/ng879"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11967536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11967536"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hiroyuki Takai, Kazuhito Naka, Yuki Okada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdf506"}], "href": "https://doi.org/10.1093/emboj/cdf506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12356735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12356735"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "C Cybulski, B Górski, T Huzarski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHEK2 is a multiorgan cancer susceptibility gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/426403"}], "href": "https://doi.org/10.1086/426403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15492928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15492928"}]}]}]}
Synonyms	RAD53, PP1425, HCDS1, CDS1, LFS2, HUCDS1, CHK2
Proteins	CHK2_HUMAN
NCBI Gene ID	11200
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CHEK2 has 13,164 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 136 datasets.

Click the + buttons to view associations for CHEK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CHEK2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CHEK2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHEK2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHEK2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CHEK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CHEK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CHEK2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CHEK2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CHEK2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CHEK2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CHEK2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CHEK2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CHEK2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CHEK2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CHEK2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHEK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CHEK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CHEK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CHEK2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CHEK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CHEK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CHEK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CHEK2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CHEK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CHEK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CHEK2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CHEK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CHEK2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CHEK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CHEK2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CHEK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate CHEK2 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CHEK2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CHEK2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CHEK2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CHEK2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CHEK2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CHEK2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CHEK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CHEK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CHEK2 protein from the curated DrugBank Drug Targets dataset.