Reviewed May 2013
What is the official name of the MSH2 gene?
The official name of this gene is “mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli).”
MSH2 is the gene's official symbol. The MSH2 gene is also known by other names, listed below.
What is the normal function of the MSH2 gene?
The MSH2 gene provides instructions for making a protein that plays an essential role in DNA repair. This protein helps fix mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MSH2 protein joins with one of two other proteins, MSH6 or MSH3 (each produced from a different gene), to form a protein complex. This complex identifies locations on the DNA where mistakes have been made during DNA replication. Another group of proteins, the MLH1-PMS2 protein complex, then repairs the errors. The MSH2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.
How are changes in the MSH2 gene related to health conditions?
- Lynch syndrome - increased risk from variations of the MSH2 gene
About 40 percent of all cases of Lynch syndrome with an identified gene mutation are associated with mutations in the MSH2 gene. Several hundred MSH2 gene mutations have been found in people with this condition. Lynch syndrome increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the endometrium (lining of the uterus), ovaries, stomach, small intestine, liver, gallbladder duct, upper urinary tract, and brain.
MSH2 gene mutations involved in Lynch syndrome may cause the production of an abnormally short or inactive MSH2 protein that cannot perform its normal function. When the MSH2 protein is absent or nonfunctional, the number of DNA mistakes that are left unrepaired during cell division increases substantially. The errors accumulate as the cells continue to divide, which may cause the cells to function abnormally, increasing the risk of tumor formation in the colon or another part of the body.
Some mutations in the MSH2 gene cause a variant of Lynch syndrome called Muir-Torre syndrome. In addition to colorectal cancer, people with this condition have an increased risk of developing several uncommon skin tumors. These rare skin tumors include sebaceous adenomas and carcinomas, which occur in glands that produce an oily substance called sebum (sebaceous glands). Multiple rapidly growing tumors called keratoacanthomas may also occur, usually on sun-exposed areas of skin.
Where is the MSH2 gene located?
Cytogenetic Location: 2p21
Molecular Location on chromosome 2: base pairs 47,630,205 to 47,710,366
The MSH2 gene is located on the short (p) arm of chromosome 2 at position 21.
More precisely, the MSH2 gene is located from base pair 47,630,205 to base pair 47,710,366 on chromosome 2.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about MSH2?
You and your healthcare professional may find the following resources about MSH2 helpful.
Educational resources - Information pages
- American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer (http://www.nchpeg.org/documents/crc/Basics%20of%20genetic%20testing.pdf)
- Cancer Medicine (sixth edition, 2003): DNA Mismatch Repair Gene Defects and HNPCC (http://www.ncbi.nlm.nih.gov/books/NBK12469/)
- Molecular Biology of the Cell (fourth edition, 2002): Defects in DNA Mismatch Repair Provide an Alternative Route to Colorectal Cancer (http://www.ncbi.nlm.nih.gov/books/NBK26902/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1211/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for MSH2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4436%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(MSH2%5BTI%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- MutS, E. COLI, HOMOLOG OF, 2 (http://omim.org/entry/609309)
- MUIR-TORRE SYNDROME (http://omim.org/entry/158320)
- NEUROFIBROMATOSIS, TYPE I (http://omim.org/entry/162200)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_MSH2.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4436)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4436)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=7325)
What other names do people use for the MSH2 gene or gene products?
- mutS (E. coli) homolog 2
- mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1)
- mutS homolog 2
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding MSH2?
cell division ;
DNA repair ;
DNA replication ;
E. coli ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005;4(4):323-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16341812?dopt=Abstract)
- Cohen MM Jr. Molecular dimensions of gastrointestinal tumors: some thoughts for digestion. Am J Med Genet A. 2003 Nov 1;122A(4):303-14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14518068?dopt=Abstract)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4436)
- Gene Review: Lynch Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1211/)
- Guillem JG, Moore HG, Palmer C, Glogowski E, Finch R, Nafa K, Markowitz AJ, Offit K, Ellis NA. A636P testing in Ashkenazi Jews. Fam Cancer. 2004;3(3-4):223-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15516845?dopt=Abstract)
- Lützen A, de Wind N, Georgijevic D, Nielsen FC, Rasmussen LJ. Functional analysis of HNPCC-related missense mutations in MSH2. Mutat Res. 2008 Oct 14;645(1-2):44-55. doi: 10.1016/j.mrfmmm.2008.08.015. Epub 2008 Sep 4. (http://www.ncbi.nlm.nih.gov/pubmed/18822302?dopt=Abstract)
- Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):919-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12621137?dopt=Abstract)
- Mitchell RJ, Farrington SM, Dunlop MG, Campbell H. Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review. Am J Epidemiol. 2002 Nov 15;156(10):885-902. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12419761?dopt=Abstract)
- Pande M, Wei C, Chen J, Amos CI, Lynch PM, Lu KH, Lucio LA, Boyd-Rogers SG, Bannon SA, Mork ME, Frazier ML. Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry. Fam Cancer. 2012 Sep;11(3):441-7. doi: 10.1007/s10689-012-9534-6. (http://www.ncbi.nlm.nih.gov/pubmed/22714864?dopt=Abstract)
- Peltomäki P. Lynch syndrome genes. Fam Cancer. 2005;4(3):227-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16136382?dopt=Abstract)
- Rishi K, Font RL. Sebaceous gland tumors of the eyelids and conjunctiva in the Muir-Torre syndrome: a clinicopathologic study of five cases and literature review. Ophthal Plast Reconstr Surg. 2004 Jan;20(1):31-6. Review. Erratum in: Ophthal Plast Reconstr Surg. 2004 May;11(5):953. (http://www.ncbi.nlm.nih.gov/pubmed/14752307?dopt=Abstract)
- South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A. The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst. 2008 Feb 20;100(4):277-81. doi: 10.1093/jnci/djm291. Epub 2008 Feb 12. (http://www.ncbi.nlm.nih.gov/pubmed/18270343?dopt=Abstract)
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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.