MMACHC (Q9Y4U1) variants and mutations

MMACHC (also known as Q9Y4U1) is a human protein-coding gene encoding a cyanocobalamin reductase / alkylcobalamin dealkylase protein. It processes intracellular cobalamin so that vitamin B12 can be converted into the active cofactors needed for methionine synthase and methylmalonyl-CoA mutase. Biallelic loss causes cblC disease, with combined methylmalonic acidemia and homocystinuria and highly variable neurologic and systemic manifestations. This analysis covers 726 MMACHC variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes Methylmalonic acidemia with homocystinuria, type cblC, methylmalonic aciduria and homocystinuria type cblC, and Methylmalonic acidemia with homocystinuria. Example MMACHC variants include M1I, M1L, and M1R.

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 MMACHC variants

Examples include M1I, M1L, M1R, M1T, M1V, E2G, E2K, E2V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.