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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed July 2011

What is the official name of the MTR gene?

The official name of this gene is “5-methyltetrahydrofolate-homocysteine methyltransferase.”

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

What is the normal function of the MTR gene?

The MTR gene provides instructions for making an enzyme called methionine synthase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Specifically, methionine synthase carries out a chemical reaction that converts the amino acid homocysteine to another amino acid called methionine. The body uses methionine to make proteins and other important compounds. To function properly, methionine synthase requires methylcobalamin (a form of vitamin B12) and another enzyme called methionine synthase reductase, which is produced from the MTRR gene.

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

homocystinuria - caused by mutations in the MTR gene

More than 20 mutations in the MTR gene have been identified in people with homocystinuria. Many of these mutations lead to the production of an abnormally small, nonfunctional version of methionine synthase. Other mutations change single amino acids in the enzyme. One of the most common mutations replaces the amino acid proline with the amino acid leucine at position 1173 (written as Pro1173Leu or P1173L), resulting in an enzyme with reduced function. Without functional methionine synthase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.

other disorders - increased risk from variations of the MTR gene

A specific version (variant) of the MTR gene has been associated with various health problems before birth. The variant replaces one building block of DNA (nucleotide) called adenine with the nucleotide guanine at position 2756 in the MTR gene (written as A2756G). This variant has been associated with an increased risk of birth defects that occur during the development of the brain and spinal cord (neural tube defects). Some studies have suggested that the variant also increases the risk of having a child with Down syndrome, which is a condition characterized by intellectual disability and associated health problems, but other studies found no increased risk. Researchers do not know why there may be a connection between the A2756G variant of the MTR gene and the risk of neural tube defects or Down syndrome. Many factors play a part in determining the risk of these complex disorders.

Where is the MTR gene located?

Cytogenetic Location: 1q43

Molecular Location on chromosome 1: base pairs 236,794,304 to 236,903,981

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The MTR gene is located on the long (q) arm of chromosome 1 at position 43.

The MTR gene is located on the long (q) arm of chromosome 1 at position 43.

More precisely, the MTR gene is located from base pair 236,794,304 to base pair 236,903,981 on chromosome 1.

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

Where can I find additional information about MTR?

You and your healthcare professional may find the following resources about MTR 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 MTR gene or gene products?

  • 5-methyltetrahydrofolate-homocysteine methyltransferase 1
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • cblG
  • cobalamin-dependent methionine synthase
  • Homocysteine-methyl tetrahydrofolate methyltransferase
  • Methionine Synthase
  • Tetrahydropteroylglutamate Methyltransferase

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

What glossary definitions help with understanding MTR?

acids ; adenine ; amino acid ; anemia ; cobalamin ; deficiency ; disability ; DNA ; enzyme ; gene ; guanine ; leucine ; megaloblastic anemia ; methionine ; methyl ; methyltransferase ; neural tube defects ; nucleotide ; proline ; syndrome ; vitamin B12

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


  • Bosco P, Guéant-Rodriguez RM, Anello G, Barone C, Namour F, Caraci F, Romano A, Romano C, Guéant JL. Methionine synthase (MTR) 2756 (A --> G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are three risk factors for having a child with Down syndrome. Am J Med Genet A. 2003 Sep 1;121A(3):219-24. (
  • Carmel R, Green R, Rosenblatt DS, Watkins D. Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program. 2003:62-81. Review. (
  • Doolin MT, Barbaux S, McDonnell M, Hoess K, Whitehead AS, Mitchell LE. Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida. Am J Hum Genet. 2002 Nov;71(5):1222-6. Epub 2002 Oct 9. (
  • Guéant-Rodriguez RM, Rendeli C, Namour B, Venuti L, Romano A, Anello G, Bosco P, Debard R, Gérard P, Viola M, Salvaggio E, Guéant JL. Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans. Neurosci Lett. 2003 Jul 3;344(3):189-92. (
  • NCBI Gene (
  • Watkins D, Ru M, Hwang HY, Kim CD, Murray A, Philip NS, Kim W, Legakis H, Wai T, Hilton JF, Ge B, Doré C, Hosack A, Wilson A, Gravel RA, Shane B, Hudson TJ, Rosenblatt DS. Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L. Am J Hum Genet. 2002 Jul;71(1):143-53. Epub 2002 May 30. (


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: July 2011
Published: February 1, 2016