|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “mutS homolog 6.”
MSH6 is the gene's official symbol. The MSH6 gene is also known by other names, listed below.
The MSH6 gene provides instructions for making a protein that plays an essential role in repairing DNA. This protein helps fix mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MSH6 protein joins with another protein called MSH2 (produced from the MSH2 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 MSH6 gene is a member of a set of genes known as the mismatch repair (MMR) genes.
Mutations in the MSH6 gene have been reported in about 10 percent of families with Lynch syndrome that have an identified gene mutation. 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. Endometrial cancer is especially common in women with Lynch syndrome caused by MSH6 gene mutations.
MSH6 gene mutations involved in this condition lead to the production of an abnormally short, nonfunctional MSH6 protein or a partially active version of the protein. When the MSH6 protein is absent or nonfunctional, the number of 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.
In a small number of people, mutations in the MSH6 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.
While Lynch syndrome is associated with a mutation in one copy of the MSH6 gene, very rarely, individuals in affected families inherit two MSH6 gene mutations, one from each parent. Most often in these cases, the same mutation occurs in both copies of the gene (a homozygous mutation). People with a homozygous MSH6 gene mutation have a syndrome distinct from Lynch syndrome. In addition to colorectal cancer, they may develop cancers of the blood (leukemia or lymphoma). Some of these individuals will also develop characteristic features of a condition known as neurofibromatosis, including noncancerous tumors that grow along nerves (neurofibromas) and light brown patches of skin called café-au-lait spots. The onset of colon cancer in these individuals is extremely early, often occurring during childhood. This syndrome involving colon cancer, leukemia or lymphoma, and neurofibromatosis is sometimes called CoLoN.
Cytogenetic Location: 2p16
Molecular Location on chromosome 2: base pairs 47,783,082 to 47,806,953
The MSH6 gene is located on the short (p) arm of chromosome 2 at position 16.
More precisely, the MSH6 gene is located from base pair 47,783,082 to base pair 47,806,953 on chromosome 2.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about MSH6 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
cancer ; cell ; cell division ; colon ; colorectal ; DNA ; DNA replication ; duct ; E. coli ; endometrial ; endometrium ; gallbladder ; gene ; homozygous ; inherit ; intestine ; leukemia ; lymphoma ; mutation ; ovarian ; protein ; rectum ; stomach ; subunit ; syndrome ; tumor
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.