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Genetics Home Reference: your guide to understanding genetic conditions
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MLH1

Reviewed April 2008

What is the official name of the MLH1 gene?

The official name of this gene is “mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli).”

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

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 fixes mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MLH1 protein joins with another protein, the PMS2 protein, to form an active protein complex. This protein 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 mutations in the MLH1 gene. Several hundred MLH1 mutations that predispose people to colorectal cancer have been found. These mutations prevent the production of MLH1 protein or lead to an altered version of this protein that does not function properly. When the MLH1 protein is absent or ineffective, the number of mistakes that are left unrepaired during cell division increases substantially. If the cells continue to divide, errors accumulate in DNA; the cells become unable to function properly and may form a tumor in the colon or another part of the body.

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, gallbladder duct, upper urinary tract, and brain.

Mutations in the MLH1 gene sometimes 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.

other cancers - caused by mutations in the MLH1 gene

Some individuals in families affected by Lynch syndrome have a mutation in both copies of the MLH1 gene. Most often, the same mutation occurs in both copies of the gene (a homozygous mutation) in each cell. People with a homozygous MLH1 mutation have a syndrome distinct from Lynch syndrome. In addition to colorectal cancer, they may develop cancers of the blood (leukemia or lymphoma). Some of these individuals will also develop noncancerous tumors that grow along nerves (neurofibromas) and have light brown patches of skin called café-au-lait spots. These two signs are characteristic of a condition known as neurofibromatosis. 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 37,034,840 to 37,092,336

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 37,034,840 to base pair 37,092,336 on chromosome 3.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about MLH1?

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

  • Educational resources - Information pages

    • Cancer Medicine (sixth edition, 2003): DNA Mismatch Repair Gene Defects and HNPCC (http://www.ncbi.nlm.nih.gov/books/NBK12469/)
    • Molecular Biology of the Cell (fourth edition, 2002): Defects in DNA Mismatch Repair Provide an Alternative Route to Colorectal Cancer (http://www.ncbi.nlm.nih.gov/books/NBK26902/)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hnpcc)

  • Gene Tests - DNA tests ordered by healthcare professionals

    • Gene Tests: Lynch Syndrome (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2622)
    • Gene Tests: MLH1-Related Lynch Syndrome (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/316509)

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

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(MLH1%5BTI%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • MutL, E. COLI, HOMOLOG OF, 1 (http://omim.org/entry/120436)
    • NEUROFIBROMATOSIS, TYPE I (http://omim.org/entry/162200)
    • MISMATCH REPAIR CANCER SYNDROME (http://omim.org/entry/276300)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_MLH1.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4292)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4292)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=7127)

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

  • COCA2
  • DNA mismatch repair protein Mlh1
  • FCC2
  • hMLH1
  • HNPCC
  • HNPCC2
  • MGC5172
  • MLH1_HUMAN
  • mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2)
  • MutL protein homolog 1

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

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 ; homologs ; homozygous ; intestine ; leukemia ; lymphoma ; mutation ; ovary ; protein ; sign ; stomach ; syndrome ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005;4(4):323-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16341812?dopt=Abstract)
  • Cohen MM Jr. Molecular dimensions of gastrointestinal tumors: some thoughts for digestion. Am J Med Genet A. 2003 Nov 1;122A(4):303-14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14518068?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4292)
  • Gene Review: Lynch Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hnpcc)
  • Jacob S, Praz F. DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie. 2002 Jan;84(1):27-47. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11900875?dopt=Abstract)
  • Marti TM, Kunz C, Fleck O. DNA mismatch repair and mutation avoidance pathways. J Cell Physiol. 2002 Apr;191(1):28-41. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11920679?dopt=Abstract)
  • Mitchell RJ, Farrington SM, Dunlop MG, Campbell H. Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review. Am J Epidemiol. 2002 Nov 15;156(10):885-902. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12419761?dopt=Abstract)
  • OMIM: MutL, E. COLI, HOMOLOG OF, 1 (http://omim.org/entry/120436)
  • Peltomäki P. Lynch syndrome genes. Fam Cancer. 2005;4(3):227-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16136382?dopt=Abstract)
  • Raevaara TE, Korhonen MK, Lohi H, Hampel H, Lynch E, Lönnqvist KE, Holinski-Feder E, Sutter C, McKinnon W, Duraisamy S, Gerdes AM, Peltomäki P, Kohonen-Ccorish M, Mangold E, Macrae F, Greenblatt M, de la Chapelle A, Nyström M. Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1. Gastroenterology. 2005 Aug;129(2):537-49. (http://www.ncbi.nlm.nih.gov/pubmed/16083711?dopt=Abstract)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2008
Published: May 21, 2012