MTHFR
Chr 1ARADmethylenetetrahydrofolate reductase
The protein catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate required for homocysteine remethylation to methionine. Mutations cause homocystinuria due to MTHFR deficiency with autosomal recessive inheritance, while certain variants increase susceptibility to neural tube defects, thromboembolism, and vascular disease. Loss-of-function mutations result in enzyme deficiency leading to elevated homocysteine levels and disrupted methionine metabolism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MTHFR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Methyl-donor Nutrient Supplementation and Methylation Profile in Lupus Patients With Obesity
ENROLLING BY INVITATIONMaternal Methyl-Nutrient Status and Infant Neurodevelopment Study
NOT YET RECRUITINGPrecision Medicine in the Treatment of Epilepsy
RECRUITINGSilent Myocardial Ischemia in Patients Undergoing Non-oncological Abdominal Surgeries
RECRUITINGOptimal Nutrition for Prevention of Hypertension in Pregnancy
ACTIVE NOT RECRUITINGEvaluation of a Genetically Determined Personalized Approach in Prescribing Biologically Active Substances in Patients With Elevated Blood Homocysteine Levels.
RECRUITINGPancreatic Cancer Genetics
RECRUITINGGenomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools