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MLH1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

MLH1 gene

The MLH1 gene provides instructions for a protein essential for DNA repair, and mutations in this gene are linked to increased cancer risks.

Normal Function

The MLH1 gene provides instructions for making a protein that plays an essential role in DNA repair. This protein helps correct errors that occur during DNA replication in preparation for cell division. The MLH1 protein joins with another protein, PMS2, to form a dimer. This complex coordinates other proteins to remove and replace incorrect DNA sequences. The MLH1 gene is classified as a mismatch repair (MMR) gene. While MLH1 can also form dimers with MLH3 or PMS1, the specific functions of these combinations are not yet well understood.

Health Conditions Related to Genetic Changes

Constitutional mismatch repair deficiency syndrome

Pathogenic variants in both copies of the MLH1 gene (one from each parent) cause constitutional mismatch repair deficiency (CMMRD) syndrome. This condition significantly increases the risk of developing cancer in early childhood, including:

  • Leukemia or lymphoma
  • Brain cancer
  • Colorectal cancer

Approximately 50 percent of people with CMMRD develop cancer by age 10, and 90 percent by age 18. Many individuals also experience changes in skin pigmentation. Because both copies of the gene are affected, the body cannot fix DNA replication errors, leading to an accumulation of mutations in all cells.

Lynch syndrome

Lynch syndrome occurs when an individual inherits one normal MLH1 gene and one MLH1 gene with a pathogenic variant. While the normal copy typically produces enough functional protein to repair DNA, problems arise if the normal copy acquires a pathogenic variant during a person's lifetime. This leads to a loss of functional MLH1 protein in specific cells, increasing the risk of various cancers, including:

  • Colorectal cancer
  • Cancer of the lining of the uterus
  • Ovarian, stomach, small intestine, gallbladder duct, upper urinary tract, and brain cancers

By age 70, people with Lynch syndrome caused by MLH1 variants have a 65 to 80 percent risk of developing cancer.

Other Names for This Gene

  • COCA2
  • FCC2
  • MLH-1

Frequently Asked Questions

CMMRD syndrome results from inheriting two mutated MLH1 copies (one from each parent) and causes a very high risk of aggressive cancers, often in early childhood, including leukemia, lymphoma, brain tumors, and colorectal cancer. Lynch syndrome, on the other hand, results from inheriting one mutated MLH1 copy. While it significantly increases cancer risk, these cancers (primarily colorectal, endometrial, ovarian, and others) typically develop in adulthood and often at younger ages than in the general population.
For individuals with an MLH1 mutation (Lynch syndrome), screening typically begins at a younger age than the general population. This includes regular colonoscopies, often starting in the 20s or early 30s, and potentially upper endoscopies. Women may be advised to have gynecologic surveillance (e.g., endometrial biopsies, transvaginal ultrasounds) or consider risk-reducing surgeries like hysterectomy and oophorectomy. Specific recommendations vary based on family history and individual risk factors, so consultation with a genetics specialist is crucial.
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.

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