MLH1

The MLH1 gene makes a protein that plays an essential role in repairing DNA. This protein fixes mistakes that are made when DNA is copied (replicated) in preparation for cell division. The MLH1 protein uses the energy molecule adenosine triphosphate (ATP) as it performs its work. The MLH1 protein becomes active in the presence of ATP when it is paired with another protein made from the PMS2 gene. This active protein complex coordinates the binding of various other proteins that repair mistakes made during DNA replication. The repairs are made by removing a section of DNA that contains the mistakes and replacing it with a correctly matched DNA sequence. The MLH1 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

The following genes are involved in the DNA mismatch repair (MMR) pathway and repair DNA that is not correctly copied before cell division.

• MLH1:mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
• MSH2:mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
• MSH6:mutS homolog 6 (E. coli)
• PMS2:PMS2 postmeiotic segregation increased 2 (S. cerevisiae)

hereditary nonpolyposis colorectal cancer - increased risk from variations of the MLH1 gene

About 40 percent of all cases of hereditary nonpolyposis colon cancer (HNPCC) with an identified mutation are associated with mutations in the MLH1 gene. Several hundred MLH1 mutations that predispose people to colorectal cancer and other associated cancers have been found. These mutations prevent the production of MLH1 protein or lead to an altered version of this protein that doesn't function properly. When the MLH1 protein is absent or working inadequately, the number of mistakes that occur in DNA during cell division increases substantially. Errors in DNA accumulate if cells continue to divide, leading to uncontrolled cell growth and the formation of a cancerous tumor.

People with a mutation in this gene also have an increased chance of developing several other types of cancer, including cancers of the endometrium (lining of the uterus), ovary, stomach, small intestine, liver and gallbladder duct, upper urinary tract, and brain. Turcot syndrome, which includes particular kinds of brain tumors, namely glioblastomas, in addition to colorectal cancer, can also be caused by mutations in the MLH1 gene.

3p21.3

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

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

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

• Educational resources - Information pages
  Mismatch Repair Genes hMLH1 and hMSH2 and Colorectal Cancer - CDC fact sheet
• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals

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

• PubMed - Recent literature
• OMIM - Genetic disorder catalog (3 links)
• Research Resources - Tools for researchers (4 links)

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How does a gene make a protein?
• How can gene mutations cause disorders?

These links provide additional genetics resources that may be useful.

• Genetics education
• Human Genome Project
• Resources for Genetic Researchers

adenosine triphosphate ; ATP ; cancer ; cell division ; colon ; colorectal ; DNA ; DNA replication ; duct ; endometrium ; gene ; glioblastoma ; homologs ; intestine ; molecule ; mutation ; protein ; segregation ; tumor

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