PMS2 gene

PMS1 homolog 2, mismatch repair system component

The PMS2 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 PMS2 protein joins with another protein called MLH1 (produced from the MLH1 gene) to form a protein complex. This complex coordinates the activities of other proteins that repair mistakes made during DNA replication. Repairs are made by removing the section of DNA that contains mistakes and replacing it with a corrected DNA sequence. The PMS2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

Mutations in the PMS2 gene have been reported in about 2 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. PMS2 gene mutations involved in this condition lead to the production of an abnormally short or inactive PMS2 protein that cannot efficiently repair mistakes made during DNA replication. 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 PMS2 gene can cause a variant of Lynch syndrome called Turcot syndrome. In addition to colorectal cancer, people with Turcot syndrome tend to develop a particular type of brain tumor called a glioblastoma.

Genetics Home Reference provides information about ovarian cancer.

While Lynch syndrome is associated with a mutation in one copy of the PMS2 gene, very rarely, individuals in affected families inherit two PMS2 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 PMS2 gene mutation have a syndrome distinct from Lynch syndrome. In addition to colorectal cancer, these individuals 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: 7p22.1, which is the short (p) arm of chromosome 7 at position 22.1

Molecular Location: base pairs 5,970,925 to 6,009,106 on chromosome 7 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 7p22.1, which is the short (p) arm of chromosome 7 at position 22.1
  • DNA mismatch repair gene homologue
  • HNPCC4
  • MLH4
  • PMS2-C terminal -like
  • PMS2 postmeiotic segregation increased 2 (S. cerevisiae)
  • PMS2CL
  • PMSL2
  • postmeiotic segregation increased (S. cerevisiae) 2