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MTHFR gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

MTHFR gene

The MTHFR gene encodes an enzyme critical for processing folate and amino acids, with specific variants linked to elevated homocysteine levels and potential risks for certain health conditions.

Normal Function

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. It is essential for a chemical reaction involving the vitamin folate (vitamin B9), converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This is the primary form of folate in the blood and is necessary to convert the amino acid homocysteine to methionine, which the body uses to make proteins and other important compounds.

Health Conditions Related to Genetic Changes

Homocystinuria

At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria, a disorder where the body cannot properly process homocysteine and methionine. This leads to a buildup of homocysteine in the blood and reduced levels of methionine. Symptoms often include:

  • Eye problems
  • Abnormal blood clotting
  • Skeletal abnormalities
  • Learning problems

Anencephaly and Spina bifida

Variations (polymorphisms) in the MTHFR gene, particularly the 677C>T variant, have been associated with a small increased risk of neural tube defects, such as anencephaly and spina bifida. These variants can result in reduced enzyme activity and hyperhomocysteinemia (elevated homocysteine levels). However, most people with these common polymorphisms do not have children with neural tube defects.

Other disorders

Polymorphisms such as 677C>T and 1298A>C have been studied as potential risk factors for various conditions, including:

  • High blood pressure (hypertension)
  • Blood clots
  • Pregnancy loss
  • Psychiatric disorders
  • Certain types of cancer
  • Vascular disease (heart disease and stroke)
  • Cleft lip and palate

Research results regarding these associations have been mixed, and it is likely that a combination of genetic and environmental factors influences the risk of developing these complex conditions.

Frequently Asked Questions

Severe MTHFR deficiency is an extremely rare, life-threatening metabolic disorder caused by rare, highly destructive mutations that reduce enzyme activity to less than 20 percent. It causes severe homocystinuria, developmental delays, microcephaly, and early vascular thrombosis. In contrast, common polymorphisms like C677T and A1298C are benign genetic variants found in a large portion of the global population; they slightly reduce enzyme efficiency but rarely cause significant disease on their own.
Major clinical organizations, including the American College of Medical Genetics and Genomics (ACMG) and the Centers for Disease Control and Prevention (CDC), do not recommend replacing folic acid with L-methylfolate for neural tube defect prevention. Folic acid is the only form of folate clinically proven in large-scale human trials to prevent neural tube defects. Unless a clinician identifies significantly elevated plasma homocysteine or a documented metabolic barrier, standard dietary folate and prenatal folic acid remain the recommended standard of care.
Current medical consensus concludes they do not. While early observational studies suggested a potential link, extensive meta-analyses have shown that common MTHFR polymorphisms alone do not independently increase the risk of deep vein thrombosis, pulmonary embolism, or recurrent pregnancy loss. Consequently, guidelines from the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) explicitly advise against routine clinical screening for MTHFR variants in workups for recurrent pregnancy loss or thrombophilia.
The most useful test is a simple fasting total plasma homocysteine level, often ordered alongside serum vitamin B12 and folate levels. Genotype alone does not predict clinical impact; a normal plasma homocysteine level demonstrates that the cellular methylation cycle is functioning adequately, meaning no specialized nutritional therapy or prescription supplementation is medically indicated.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.