Reviewed July 2011
What is the official name of the MTHFR gene?
The official name of this gene is “methylenetetrahydrofolate reductase (NAD(P)H).”
MTHFR is the gene's official symbol. The MTHFR gene is also known by other names, listed below.
Read more about gene names and symbols on the About page.
What is the normal function of the MTHFR gene?
The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the B-vitamin folate (also called folic acid or vitamin B9). Specifically, this enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.
How are changes in the MTHFR gene related to health conditions?
homocystinuria - caused by mutations in the MTHFR gene
At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria. Most of these mutations change single amino acids in methylenetetrahydrofolate reductase. These changes impair the function of the enzyme, and some cause the enzyme to be turned off (inactivated). Other mutations lead to the production of an abnormally small, nonfunctional version of the enzyme. Without functional methylenetetrahydrofolate reductase, 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.
anencephaly - associated with the MTHFR gene
Several variations (polymorphisms) in the MTHFR gene have been associated with an increased risk of neural tube defects (NTDs), a group of birth defects that occur during the development of the brain and spinal cord. Anencephaly is one of the most common types of neural tube defect. Affected individuals are missing large parts of the brain and have missing or incompletely formed skull bones.
The most well-studied polymorphism related to the risk of neural tube defects changes a single DNA building block (nucleotide) in the MTHFR gene. Specifically, it replaces the nucleotide cytosine with the nucleotide thymine at position 677 (written as 677C>T). This variant, which is relatively common in many populations worldwide, produces a form of methylenetetrahydrofolate reductase that has reduced activity at higher temperatures (thermolabile). People with the thermolabile form of the enzyme have increased levels of homocysteine in their blood.
It is unclear how variations in the MTHFR gene increase the likelihood of neural tube defects. However, the increased risk may be related to differences in the ability of methylenetetrahydrofolate reductase to process folate. A shortage of this vitamin is an established risk factor for neural tube defects.
spina bifida - associated with the MTHFR gene
Polymorphisms in the MTHFR gene are also associated with an increased risk of spina bifida, another common type of neural tube defect. In people with this condition, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. As a result, part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage.
As described above, variations in the MTHFR gene may increase the risk of neural tube defects by changing the ability of methylenetetrahydrofolate reductase to process folate.
- other disorders - increased risk from variations of the MTHFR gene
Polymorphisms in the MTHFR gene have also been studied as possible risk factors for a variety of common conditions. These include heart disease, stroke, high blood pressure (hypertension), high blood pressure during pregnancy (preeclampsia), an eye disorder called glaucoma, psychiatric disorders, and certain types of cancer. The 677C>T polymorphism in the MTHFR gene has also been suggested as a risk factor for cleft lip and palate, a birth defect in which there is a split in the upper lip and an opening in the roof of the mouth. Studies of MTHFR gene variations in people with these disorders have had mixed results, with associations found in some studies but not in others. Therefore, it remains unclear what role changes in the MTHFR gene play in determining the risk of these complex conditions.
Where is the MTHFR gene located?
Cytogenetic Location: 1p36.3
Molecular Location on chromosome 1: base pairs 11,785,729 to 11,806,102
The MTHFR gene is located on the short (p) arm of chromosome 1 at position 36.3.
More precisely, the MTHFR gene is located from base pair 11,785,729 to base pair 11,806,102 on chromosome 1.
See How do geneticists indicate the location of a gene? in the Handbook.
Where can I find additional information about MTHFR?
You and your healthcare professional may find the following resources about MTHFR 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 MTHFR gene or gene products?
- 5,10-methylenetetrahydrofolate reductase (NADPH)
- methylenetetrahydrofolate reductase
Where can I find general information about genes?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding MTHFR?
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? in the Handbook.