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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 MTRR gene?

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

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

What is the normal function of the MTRR gene?

The MTRR gene provides instructions for making an enzyme called methionine synthase reductase. This enzyme is required for the proper function of another enzyme called methionine synthase. Methionine synthase helps process amino acids, which are the building blocks of proteins. Specifically, it converts the amino acid homocysteine to another amino acid called methionine. After a period of being turned on (active), methionine synthase turns off (becomes inactive). Methionine synthase reductase reactivates methionine synthase so the enzyme can continue to produce methionine.

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

homocystinuria - caused by mutations in the MTRR gene

At least 20 mutations in the MTRR gene have been identified in people with homocystinuria. Some of these mutations change single amino acids in methionine synthase reductase. Other mutations lead to an abnormally small, nonfunctional version of the enzyme. All these mutations prevent the enzyme from functioning normally. Without methionine synthase reductase, methionine synthase cannot convert homocysteine 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 MTRR gene

A specific version (variant) of the MTRR gene may be associated with an increased risk of various health problems before birth. The variant replaces a building block of DNA (nucleotide) called adenine with the nucleotide guanine at position 66 of the MTRR gene (written as A66G). This variant is associated with birth defects that occur during the development of the brain and spinal cord (neural tube defects). This variant may also increase the risk of having a child with Down syndrome, a condition characterized by intellectual disability and associated health problems. Researchers have not determined why there may be a connection between the A66G variant of the MTRR gene and the risk of neural tube defects or Down syndrome. Many factors play a part in determining the risk of these disorders.

Where is the MTRR gene located?

Cytogenetic Location: 5p15.31

Molecular Location on chromosome 5: base pairs 7,851,186 to 7,901,124

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

The MTRR gene is located on the short (p) arm of chromosome 5 at position 15.31.

The MTRR gene is located on the short (p) arm of chromosome 5 at position 15.31.

More precisely, the MTRR gene is located from base pair 7,851,186 to base pair 7,901,124 on chromosome 5.

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

Where can I find additional information about MTRR?

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

  • cblE
  • methionine synthase reductase
  • MSR

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

What glossary definitions help with understanding MTRR?

acids ; adenine ; amino acid ; anemia ; disability ; DNA ; enzyme ; gene ; guanine ; megaloblastic anemia ; methionine ; methyltransferase ; neural tube defects ; nucleotide ; syndrome

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


  • 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. (
  • Hobbs CA, Sherman SL, Yi P, Hopkins SE, Torfs CP, Hine RJ, Pogribna M, Rozen R, James SJ. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet. 2000 Sep;67(3):623-30. Epub 2000 Aug 7. (
  • NCBI Gene (
  • Vilaseca MA, Vilarinho L, Zavadakova P, Vela E, Cleto E, Pineda M, Coimbra E, Suormala T, Fowler B, Kozich V. CblE type of homocystinuria: mild clinical phenotype in two patients homozygous for a novel mutation in the MTRR gene. J Inherit Metab Dis. 2003;26(4):361-9. (
  • Wilson A, Leclerc D, Rosenblatt DS, Gravel RA. Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism. Hum Mol Genet. 1999 Oct;8(11):2009-16. (
  • Zavadakova P, Fowler B, Zeman J, Suormala T, Pristoupilová K, Kozich V, Zavad'áková P. CblE type of homocystinuria due to methionine synthase reductase deficiency: clinical and molecular studies and prenatal diagnosis in two families. J Inherit Metab Dis. 2002 Oct;25(6):461-76. Erratum in: J Inherit Metab Dis. 2003;26(1):95. (


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