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MSH2 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

MSH2 gene

The MSH2 gene plays an essential role in DNA repair, and pathogenic variants in this gene are linked to hereditary cancer syndromes including Lynch syndrome and CMMRD.

Normal Function

The MSH2 gene provides instructions for making a protein that plays an essential role in repairing DNA. This protein helps correct errors that are made when DNA is copied in preparation for cell division, a process called DNA replication. The MSH2 protein joins with another protein to form a two-protein complex called a dimer. This complex identifies locations where errors have been made during DNA replication. The MSH2 dimer, together with another dimer and additional proteins, makes the repairs by replacing the section of DNA that contains an error with a corrected DNA sequence. The MSH2 gene is one of a set of genes called mismatch repair (MMR) genes.

Health Conditions Related to Genetic Changes

Constitutional mismatch repair deficiency syndrome

Pathogenic variants in the MSH2 gene have been associated with a condition called constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD greatly increases a person's risk of developing cancer throughout their lifetime, beginning in early childhood. The most common cancers that occur in people with CMMRD are cancers of the blood (leukemia or lymphoma), brain, and colon and rectum (collectively referred to as colorectal cancer). Approximately 50 percent of people with CMMRD will develop cancer by age 10, and 90 percent will develop cancer by age 18. Many people with CMMRD develop additional features, including changes in skin coloring (pigmentation).

People must inherit a pathogenic variant in both copies of the MSH2 gene (one from each parent) to have CMMRD. Because both copies are affected, the production of functional MSH2 protein is impaired in all cells of the body, causing DNA errors to accumulate and increasing cancer risk.

Lynch syndrome

Pathogenic variants in the MSH2 gene can also cause a condition called Lynch syndrome. Lynch syndrome increases the risk of many types of cancer, particularly colorectal cancer and cancer of the lining of the uterus. People with Lynch syndrome also have an increased risk of cancers of the ovaries, stomach, small intestine, gallbladder ducts, upper urinary tract, and brain. By age 70, the risk of developing cancer is approximately 77 percent in people who have Lynch syndrome caused by variants in the MSH2 gene.

People with Lynch syndrome typically inherit a normal MSH2 gene from one parent and an MSH2 gene with a pathogenic variant from the other. If the normal copy of the gene acquires a pathogenic variant during a person’s lifetime, those specific cells will no longer produce enough functional MSH2 protein to repair DNA, increasing the risk of cancer.

Some variants in the MSH2 gene cause a form 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, such as sebaceous adenomas, carcinomas, and keratoacanthomas.

Other Names for This Gene

  • COCA1
  • FCC1
  • MSH-2

Frequently Asked Questions

Lynch syndrome is an autosomal dominant condition caused by a pathogenic variant in one copy of the MSH2 gene, leading to an increased risk of colorectal and endometrial cancers typically appearing in adulthood. Constitutional Mismatch Repair Deficiency (CMMRD) syndrome is a much rarer, autosomal recessive condition where a person inherits pathogenic variants in both copies of the MSH2 gene. CMMRD presents with significantly higher cancer risks, including childhood leukemias and brain tumors, often starting in early childhood.
Genetic testing for MSH2 and other mismatch repair genes is generally recommended if there is a strong family history of early-onset colorectal cancer, endometrial cancer, or other Lynch syndrome-associated cancers. A genetic counselor can evaluate your specific family tree to determine if testing is appropriate. It is important to test an affected family member first if possible, as testing an unaffected individual may yield a negative result that does not rule out the family risk.
Individuals with Lynch syndrome due to MSH2 mutations have a significantly elevated lifetime risk of colorectal cancer, endometrial cancer, ovarian cancer, gastric cancer, and urinary tract cancers. The risk is highest for colorectal and endometrial cancers. For those with CMMRD, the risk extends to childhood cancers such as leukemia, lymphoma, and brain tumors, in addition to the adult-onset cancers seen in Lynch syndrome.
For individuals with Lynch syndrome, guidelines typically recommend starting colorectal cancer screening with colonoscopy every 1 to 2 years beginning at age 20 to 25. For women, annual endometrial cancer screening, which may include transvaginal ultrasound and endometrial biopsy, is often recommended starting at age 30 to 35. Regular skin checks and awareness of symptoms in other organs are also part of comprehensive management.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.