MTHFS
Chr 15ARmethenyltetrahydrofolate synthetase
Also known as: HsT19268, NEDMEHM
The protein catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate and helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for purine, thymidine and amino acid biosynthesis. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination. The gene shows tolerance to loss-of-function variants (LOEUF 1.548), suggesting the pathogenic variants may have other effects on protein function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MTHFS · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools