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CHEK2 (CHK2 checkpoint homolog (S. pombe))

Written2004-05Nancy Uhrhammer
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France

(Note : for Links provided by Atlas : click)


Alias (NCBI)CHK2
HGNC Alias symbCDS1
HGNC Previous nameRAD53
HGNC Previous nameCHK2 (checkpoint, S.pombe) homolog
 CHK2 checkpoint homolog (S. pombe)
LocusID (NCBI) 11200
Atlas_Id 312
Location 22q12.1  [Link to chromosome band 22q12]
Location_base_pair Starts at 28687743 and ends at 28741834 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CHEK2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AHI1 (6q23.3)::CHEK2 (22q12.1)CHEK2 (22q12.1)::PARVB (22q13.31)PPP2R2A (8p21.2)::CHEK2 (22q12.1)


Description 17 exons spanning 57 kb
Transcription Two isoforms are expressed, isoform a (2547nt) includes all 17 exons, while isoform b (2460 nt) does not include exon 12, deleting 87nt (29 codons) from the mRNA. The translation start site is in exon 4.


Description 61 kDa. Isoform a: 543 amino acids; isoform b: 514 amino acids. Contains FHA and ser/thr kinase domains. Molecular studies of Chk2 typically do not distinguish between the different isoforms.
Expression All tissues tested.
Localisation nuclear
Function Chk2 plays a role in the DNA damage signal cascade, especially in response to double-strand breaks. After detection of DNA damage, Chk2 is phosphorylated on Thr-68 by ATM and ATR. Thus activated, Chk2 targets p53 for phosphorylation on Ser20, releasing p53 from its inhibitor MDM2 and allowing transcriptional activation of genes responsible for cell cycle arrest, such as p21waf1/cip1, as well as initiation of apoptosis. In S phase, Chk2 phosphorylates Cdc25A on Ser123, targeting it for degradation and making it unavailable for the activation of cdk2, thus inhibiting the advance of S phase. In G2 phase, Chk2 phosphorylates Ser216 of Cdc25C, blocking entry into mitosis.

Chk2 is also involved in the regulation of BRCA1. Under normal conditions the two proteins are associated; after irradiation Chk2 phosphorylates Ser988 of BRCA1. This step is required for their dissociation, and the liberated BRCA1 participates directly in DNA repair and cell cycle arrest.

Finally, Chk2 can provoke apoptosis independently of p53, for example via phosphorylation of PML.

Homology 26 % identical to the Rad53 S. cereviscea homolog. The FHA and kinase domains are particularly conserved.


Germinal The northern european founder mutation "1100delC" is the most common found in breast cancer families. Other small deletions, stops, and missense mutations in the FHA or kinase domains such as Arg145Trp and Ile157Thr are rare in cancer families but not found in controls. The 1100delC mutation appears to increase the penetrance of mutations in certain other breast cancer genes, notably BRCA2. It should be noted that the publications describing "1100delC" have used the A of the initiation codon as nucleotide 1. This mutation thus corresponds to position 1861 in the complete, isoform a mRNA.
Somatic Missense mutations in the FHA and kinase domains as well as frameshifts and nonsense mutations have been found at low frequencies in osteosarcoma and more rarely in carcinomas of the ovary, lung, and vulva. Reduced or missing protein expression has been observed in some cases of non-Hodgkins lymphoma, although neither mutation nor silencing of the gene by methylation was detected.

Implicated in

Entity Li-Fraumeni, Li-Fraumeni-like syndrome, somatic osteosarcoma and familial aggregations of breast cancer and colon cancer.
Note The importance of Chk2 mutations in hereditary cancer risk is controversial, as some studies have failed to show an excess of mutations in selected populations, such as male breast cancer and patients with multiple colorectal adenomas developing colon cancer. In addition, some studies of breast cancer families suggest that only the relatively frequent 1100delC mutation is significant.
Prognosis No known association with the clinical parameters of solid tumors. There is a possible association with more agressive non-Hodgkins lymphomas.


DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis.
Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY
Oncogene. 1999 ; 18 (55) : 7883-7899.
PMID 10630641
Contribution of the CHEK2 1100delC variant to risk of multiple colorectal adenoma and carcinoma.
Lipton L, Fleischmann C, Sieber OM, Thomas HJ, Hodgson SV, Tomlinson IP, Houlston RS
Cancer letters. 2003 ; 200 (2) : 149-152.
PMID 14568168
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
Matsuoka S, Huang M, Elledge SJ
Science (New York, N.Y.). 1998 ; 282 (5395) : 1893-1897.
PMID 9836640
Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors.
Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, Koeffler HP
Genes, chromosomes & cancer. 2002 ; 33 (1) : 17-21.
PMID 11746983
Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility.
Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG, Eccles D, Meijers C, Lohman F, Klijn J, van den Ouweland A, Futreal PA, Nathanson KL, Weber BL, Easton DF, Stratton MR, Breast Cancer Linkage Consortium, Rahman N
American journal of human genetics. 2003 ; 72 (4) : 1023-1028.
PMID 12610780
CHEK2 1100delC is not a risk factor for male breast cancer population.
Syrjäkoski K, Kuukasjä T, Auvinen A, Kallioniemi OP
International journal of cancer. Journal international du cancer. 2004 ; 108 (3) : 475-476.
PMID 14648717
p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition.
Vahteristo P, Tamminen A, Karvinen P, Eerola H, Eklund C, Aaltonen LA, Blomqvist C, Aittomäki K, Nevanlinna H
Cancer research. 2001 ; 61 (15) : 5718-5722.
PMID 11479205


This paper should be referenced as such :
Uhrhammer, N. CHEK2 (CHK2 checkpoint homolog (S
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):191-192.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Therapy-Related Hematopoietic Neoplasia

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 3 ]
  Familial nervous system tumour syndromes Hereditary breast cancer Li-Fraumeni syndrome

External links

HGNC (Hugo)CHEK2   16627
LRG (Locus Reference Genomic)LRG_302
Entrez_Gene (NCBI)CHEK2    checkpoint kinase 2
AliasesCDS1; CHK2; HuCds1; LFS2; 
PP1425; RAD53; hCds1
GeneCards (Weizmann)CHEK2
Ensembl hg19 (Hinxton)ENSG00000183765 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000183765 [Gene_View]  ENSG00000183765 [Sequence]  chr22:28687743-28741834 [Contig_View]  CHEK2 [Vega]
ICGC DataPortalENSG00000183765
TCGA cBioPortalCHEK2
Genatlas (Paris)CHEK2
SOURCE (Princeton)CHEK2
Genetics Home Reference (NIH)CHEK2
Genomic and cartography
GoldenPath hg38 (UCSC)CHEK2  -     chr22:28687743-28741834 -  22q12.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CHEK2  -     22q12.1   [Description]    (hg19-Feb_2009)
GoldenPathCHEK2 - 22q12.1 [CytoView hg19]  CHEK2 - 22q12.1 [CytoView hg38]
Genome Data Viewer NCBICHEK2 [Mapview hg19]  
OMIM114480   176807   259500   604373   609265   
Gene and transcription
Genbank (Entrez)AB040105 AB164374 AF086904 AF096279 AF174135
RefSeq transcript (Entrez)NM_001005735 NM_001257387 NM_001349956 NM_007194 NM_145862
Consensus coding sequences : CCDS (NCBI)CHEK2
Gene ExpressionCHEK2 [ NCBI-GEO ]   CHEK2 [ EBI - ARRAY_EXPRESS ]   CHEK2 [ SEEK ]   CHEK2 [ MEM ]
Gene Expression Viewer (FireBrowse)CHEK2 [ Firebrowse - Broad ]
GenevisibleExpression of CHEK2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)11200
GTEX Portal (Tissue expression)CHEK2
Human Protein AtlasENSG00000183765-CHEK2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CHEK2
Human Protein Atlas [tissue]ENSG00000183765-CHEK2 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:15:00 CEST 2021

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