MTHFD1

Chr 14AR

methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1

Also known as: CIMAH, MTHFC, MTHFD

NCBI Gene: 4522 ENSG00000100714 UniProt: P11586 OMIM: 172460

This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Neural tube defects, folate-sensitive, susceptibility to}MIM #601634

Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemiaMIM #617780

UniProtColorectal cancer

Clinical highlights

Gene-disease validity (ClinGen)

combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

Mechanism· predicted