MTHFR (P42898) variants and mutations

MTHFR (also known as P42898) is a human protein-coding gene encoding a methylenetetrahydrofolate reductase (NADPH) protein. It generates 5-methyltetrahydrofolate for remethylation of homocysteine to methionine, linking folate metabolism with methyl-group supply. Severe biallelic deficiency causes homocystinuria with neurologic and thrombotic complications, while common variants produce much smaller effects on homocysteine. This analysis covers 1,345 MTHFR variants and mutations. Of these, 58% have computational variant effect predictions. Disease context includes homocystinuria due to methylene tetrahydrofolate reductase deficiency, schizophrenia, and neural tube defects, folate-sensitive. Example MTHFR variants include M1?, M1K, and V2A.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable MTHFR variants

Examples include M1?, M1K, V2A, V2M, N3K, E4K, E4Q, R6G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.