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Reviewed October 2015

What is the official name of the MLH1 gene?

The official name of this gene is “mutL homolog 1.”

MLH1 is the gene's official symbol. The MLH1 gene is also known by other names, listed below.

Read more about gene names and symbols on the About page.

What is the normal function of the MLH1 gene?

The MLH1 gene provides instructions for making a protein that plays an essential role in DNA repair. This protein helps fix mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MLH1 protein joins with another protein called PMS2 (produced from the PMS2 gene), to form a protein complex. This complex coordinates the activities of other proteins that repair mistakes made during DNA replication. The repairs are made by removing a section of DNA that contains mistakes and replacing the section with a corrected DNA sequence. The MLH1 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

How are changes in the MLH1 gene related to health conditions?

Lynch syndrome - increased risk from variations of the MLH1 gene

About 50 percent of all cases of Lynch syndrome with an identified gene mutation are associated with inherited mutations in the MLH1 gene. Several hundred MLH1 gene mutations have been found in people with this condition. 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.

MLH1 gene mutations involved in this condition prevent the production of the MLH1 protein or lead to an altered version of this protein that does not function properly. When the MLH1 protein is absent or nonfunctional, the number of DNA 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.

Some mutations in the MLH1 gene 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.

Another variant of Lynch syndrome, called Muir-Torre syndrome, can also be caused by mutations in the MLH1 gene. 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.

ovarian cancer - increased risk from variations of the MLH1 gene

Inherited changes in the MLH1 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.

other cancers - increased risk from variations of the MLH1 gene

While Lynch syndrome is associated with a mutation in one copy of the MLH1 gene, very rarely, individuals in affected families inherit two MLH1 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 MLH1 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.

Where is the MLH1 gene located?

Cytogenetic Location: 3p21.3

Molecular Location on chromosome 3: base pairs 36,993,350 to 37,050,846

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBIThis link leads to a site outside Genetics Home Reference.)

The MLH1 gene is located on the short (p) arm of chromosome 3 at position 21.3.

The MLH1 gene is located on the short (p) arm of chromosome 3 at position 21.3.

More precisely, the MLH1 gene is located from base pair 36,993,350 to base pair 37,050,846 on chromosome 3.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about MLH1?

You and your healthcare professional may find the following resources about MLH1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the MLH1 gene or gene products?

  • COCA2
  • FCC2
  • hMLH1
  • HNPCC2
  • mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2)
  • mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
  • MutL protein homolog 1

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding MLH1?

cancer ; cell ; cell division ; colon ; colorectal ; DNA ; DNA repair ; DNA replication ; duct ; E. coli ; endometrium ; gallbladder ; gene ; glioblastoma ; homozygous ; inherit ; inherited ; intestine ; leukemia ; lymphoma ; mutation ; ovarian ; population ; protein ; rectum ; stomach ; syndrome ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (14 links)


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? in the Handbook.

Reviewed: October 2015
Published: February 8, 2016