MSH2 gene

mutS homolog 2

The MSH2 gene provides instructions for making a protein that plays an essential role in DNA repair. This protein helps fix errors 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 errors 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.

About 40 percent of all cases of Lynch syndrome with an identified gene mutation are associated with inherited mutations in the MSH2 gene. 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 errors 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.

Inherited changes in the MSH2 gene increase the risk of developing ovarian cancer, as well as other types of cancer, as part of Lynch syndrome (described above). Women with Lynch syndrome have an 8 to 10 percent chance of developing ovarian cancer in their lifetimes, as compared with 1.6 percent in the general population.

Cytogenetic Location: 2p21-p16.3, which is the short (p) arm of chromosome 2 between positions 21 and 16.3

Molecular Location: base pairs 47,403,067 to 47,634,501 on chromosome 2 (Homo sapiens Updated Annotation Release 109.20200228, GRCh38.p13) (NCBI)

Cytogenetic Location: 2p21-p16.3, which is the short (p) arm of chromosome 2 between positions 21 and 16.3
  • COCA1
  • HNPCC1
  • mutS (E. coli) homolog 2
  • mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1)
  • mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)