Reviewed May 2013
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.
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 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.
- 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 36,993,349 to 37,050,845
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 36,993,349 to base pair 37,050,845 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
- American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer (http://www.nchpeg.org/documents/crc/Basics%20of%20genetic%20testing.pdf)
- 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/books/NBK1211)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for MLH1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4292%5Bgeneid%5D)
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=%28MLH1%5BTI%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- MISMATCH REPAIR CANCER SYNDROME (http://omim.org/entry/276300)
- MUIR-TORRE SYNDROME (http://omim.org/entry/158320)
- MutL, E. COLI, HOMOLOG OF, 1 (http://omim.org/entry/120436)
- NEUROFIBROMATOSIS, TYPE I (http://omim.org/entry/162200)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/MLH1ID149ch3p21.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=7127)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4292)
What other names do people use for the MLH1 gene or gene products?
- mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2)
- mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
- 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?
cell division ;
DNA repair ;
DNA replication ;
E. coli ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Andersen SD, Liberti SE, Lützen A, Drost M, Bernstein I, Nilbert M, Dominguez M, Nyström M, Hansen TV, Christoffersen JW, Jäger AC, de Wind N, Nielsen FC, Tørring PM, Rasmussen LJ. Functional characterization of MLH1 missense variants identified in Lynch syndrome patients. Hum Mutat. 2012 Dec;33(12):1647-55. doi: 10.1002/humu.22153. Epub 2012 Jul 23. (http://www.ncbi.nlm.nih.gov/pubmed/22753075?dopt=Abstract)
- 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)
- Dowty JG, Win AK, Buchanan DD, Lindor NM, Macrae FA, Clendenning M, Antill YC, Thibodeau SN, Casey G, Gallinger S, Marchand LL, Newcomb PA, Haile RW, Young GP, James PA, Giles GG, Gunawardena SR, Leggett BA, Gattas M, Boussioutas A, Ahnen DJ, Baron JA, Parry S, Goldblatt J, Young JP, Hopper JL, Jenkins MA. Cancer risks for MLH1 and MSH2 mutation carriers. Hum Mutat. 2013 Mar;34(3):490-7. doi: 10.1002/humu.22262. (http://www.ncbi.nlm.nih.gov/pubmed/23255516?dopt=Abstract)
- Gene Review: Lynch Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1211)
- Lebrun C, Olschwang S, Jeannin S, Vandenbos F, Sobol H, Frenay M. Turcot syndrome confirmed with molecular analysis. Eur J Neurol. 2007 Apr;14(4):470-2. (http://www.ncbi.nlm.nih.gov/pubmed/17389002?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)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4292)
- Pande M, Wei C, Chen J, Amos CI, Lynch PM, Lu KH, Lucio LA, Boyd-Rogers SG, Bannon SA, Mork ME, Frazier ML. Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry. Fam Cancer. 2012 Sep;11(3):441-7. doi: 10.1007/s10689-012-9534-6. (http://www.ncbi.nlm.nih.gov/pubmed/22714864?dopt=Abstract)
- 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)
- South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A. The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst. 2008 Feb 20;100(4):277-81. doi: 10.1093/jnci/djm291. Epub 2008 Feb 12. (http://www.ncbi.nlm.nih.gov/pubmed/18270343?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.