Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions  
 
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

CHEK2

CHK2 checkpoint homolog (S. pombe)

What is the normal function of the CHEK2 gene?

The CHEK2 gene is believed to be a tumor suppressor gene. This means that the protein made by the gene regulates the cycle of cell division by keeping cells from growing and dividing too fast or in an uncontrolled way.

The CHEK2 protein is activated when the DNA in a cell becomes damaged or when DNA strands break. DNA can be damaged by radiation or chemicals, but breaks in DNA strands also occur naturally when chromosomes exchange genetic material. The CHEK2 protein interacts with another tumor suppressor, tumor protein p53 (made by the TP53 gene), to stop the cycle of cell division in response to DNA damage. The CHEK2 protein also regulates the protein made by the BRCA1 gene (a tumor suppressor gene associated with an increased risk of breast cancer). These proteins play important roles in determining whether a damaged cell will undergo programmed cell death (apoptosis) or repair the damaged DNA. This process prevents cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.

What conditions are related to the CHEK2 gene?

breast cancer - increased risk from variations of the CHEK2 gene

A specific mutation in the CHEK2 gene is associated with a moderately increased risk of breast cancer. The mutation is a deletion of a single nucleotide (the building material of DNA) at position 1100 of the CHEK2 gene. (This mutation can be written as 1100delC.) The 1100delC mutation leads to the production of an abnormally short, nonfunctional protein. Without the CHEK2 protein, cells are unable to regulate cell division properly. As a result, DNA damage accumulates, and cells can divide without control or order. If the cycle of cell division is not tightly controlled, cancerous tumors can develop.

Li-Fraumeni syndrome - associated with the CHEK2 gene

Mutations in the CHEK2 gene have been identified in several families with cancers characteristic of Li-Fraumeni syndrome. The 1100delC mutation was identified in one of these families. Although mutations in the CHEK2 gene may be associated with an increased risk of some cancers, it is uncertain whether they cause Li-Fraumeni syndrome.

other cancers - associated with the CHEK2 gene

Mutations in the CHEK2 gene have also been found in several other types of hereditary and sporadic (not inherited) cancers. Research studies have associated CHEK2 mutations with prostate, lung, and ovarian cancers; brain tumors; and osteosarcomas.

Where is the CHEK2 gene located?

22q12.1

The CHEK2 gene is located on the long (q) arm of chromosome 22 at position 12.1.

The CHEK2 gene is located on the long (q) arm of chromosome 22 at position 12.1.

See "How do geneticists indicate the location of a gene?" in the Handbook (http://ghr.nlm.nih.gov/info=basics/show/gene_location).

Where can I find information about CHEK2?

You and your healthcare professional may find the following resources about CHEK2 helpful.

  • Gene Reviews - Clinical summary (http://www.genetests.org/query?dz=li-fraumeni)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=2856)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://ghr.nlm.nih.gov/gene=chek2/show/PubMed)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604373)
  • Research Resources - Tools for researchers
    • GeneCards (http://genecards.weizmann.ac.il/cgi-bin/cards/carddisp?CHEK2)
    • HUGO Gene Nomenclature Committee (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/get_data.pl?hgnc_id=16627)
    • LocusLink (http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=11200)

What other names do people use for the CHEK2 gene or gene products?

  • CDS1
  • Cds1 kinase
  • checkpoint-like protein CHK2
  • CHK2
  • CHK2_HUMAN
  • Chk2 protein kinase
  • hCds1 protein
  • hCHK2
  • HuCds1
  • RAD53
  • serine/threonine-protein kinase CHK2

See "How are genetic conditions and genes named?" in the Handbook (http://ghr.nlm.nih.gov/info=mutations_and_disorders/show/naming).

What glossary definitions help with understanding CHEK2?

apoptosis ; cancer ; cell division ; chromosome ; deletion ; DNA ; DNA damage ; gene ; homologs ; kinase ; mutation ; nucleotide ; osteosarcoma ; prostate ; protein ; Radiation ; serine ; sporadic ; threonine ; tumor ; tumor suppressor gene

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/ghr/glossary/Glossary).

 
Sources for this page

  • Bartek J, Falck J, Lukas J. CHK2 kinase--a busy messenger. Nat Rev Mol Cell Biol. 2001 Dec;2(12):877-86. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=11733767)
  • Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999 Dec 24;286(5449):2528-31. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=10617473)
  • Dong X, Wang L, Taniguchi K, Wang X, Cunningham JM, McDonnell SK, Qian C, Marks AF, Slager SL, Peterson BJ, Smith DI, Cheville JC, Blute ML, Jacobsen SJ, Schaid DJ, Tindall DJ, Thibodeau SN, Liu W. Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet. 2003 Feb;72(2):270-80. Epub 2003 Jan 17. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=12533788)
  • Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, van Veghel-Plandsoen M, Elstrodt F, van Duijn C, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton D, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Evans DG, Houlston R, Murday V, Narod S, Peretz T, Peto J, Phelan C, Zhang HX, Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson KL, Weber B, Rahman N, Stratton MR; CHEK2-Breast Cancer Consortium. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002 May;31(1):55-9. Epub 2002 Apr 22. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=11967536)
  • Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, Koeffler HP. Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Genes Chromosomes Cancer. 2002 Jan;33(1):17-21. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=11746983)
  • Seppala EH, Ikonen T, Mononen N, Autio V, Rokman A, Matikainen MP, Tammela TL, Schleutker J. CHEK2 variants associate with hereditary prostate cancer. Br J Cancer. 2003 Nov 17;89(10):1966-70. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=14612911)
  • Sodha N, Houlston RS, Bullock S, Yuille MA, Chu C, Turner G, Eeles RA. Increasing evidence that germline mutations in CHEK2 do not cause Li-Fraumeni syndrome. Hum Mutat. 2002 Dec;20(6):460-2. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=12442270)
  • Sodha N, Houlston RS, Williams R, Yuille MA, Mangion J, Eeles RA. A robust method for detecting CHK2/RAD53 mutations in genomic DNA. Hum Mutat. 2002 Feb;19(2):173-7. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=11793476)
  • The CHEK2 Breast Cancer Case-Control Consortium. CHEK2*1100delC and Susceptibility to Breast Cancer: A Collaborative Analysis Involving 10,860 Breast Cancer Cases and 9,065 Controls from 10 Studies. Am J Hum Genet. 2004 Jun;74(6):1175-1182. Epub 2004 Apr 30. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=15122511)
  • Vahteristo P, Bartkova J, Eerola H, Syrjakoski K, Ojala S, Kilpivaara O, Tamminen A, Kononen J, Aittomaki K, Heikkila P, Holli K, Blomqvist C, Bartek J, Kallioniemi OP, Nevanlinna H. A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet. 2002 Aug;71(2):432-8. Epub 2002 Jul 28. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=12094328)
  • Varley J, Haber DA. Familial breast cancer and the hCHK2 1100delC mutation: assessing cancer risk. Breast Cancer Res. 2003;5(3):123-5. Epub 2003 Feb 20. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db;=pubmed&dopt;=Abstract&list;_uids=12793891)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See "How can I find a genetics professional in my area?" in the Handbook (http://ghr.nlm.nih.gov/info=consultation/show/finding_professional).
 
Last Comprehensive Review: July 2004
Updated: July 27, 2004
Published: October 18, 2004
Contact NLM Customer ServiceThis link leads to a site outside Genetics Home Reference.
Lister Hill National Center for Biomedical CommunicationsThis link leads to a site outside Genetics Home Reference.
U.S. National Library of MedicineThis link leads to a site outside Genetics Home Reference., National Institutes of HealthThis link leads to a site outside Genetics Home Reference., Department of Health & Human ServicesThis link leads to a site outside Genetics Home Reference.
Freedom of Information ActThis link leads to a site outside Genetics Home Reference. CopyrightThis link leads to a site outside Genetics Home Reference. PrivacyThis link leads to a site outside Genetics Home Reference. AccessibilityThis link leads to a site outside Genetics Home Reference. FirstGov.govThis link leads to a site outside Genetics Home Reference.
For selection criteria for web links, see Genetics Home Reference at http://ghr.nlm.nih.gov/
This link leads to a site outside Genetics Home Reference. Indicates a page outside Genetics Home Reference.