MTHFD1
Description
The MTHFD1 (methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1) is a protein-coding gene located on chromosome 14.
The MTHFD1 gene, located on chromosome 14, encodes a protein with three distinct enzymatic activities: methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formate–tetrahydrofolate ligase. These activities catalyze the interconversion of 1-carbon derivatives of tetrahydrofolate, which are essential for methionine, thymidylate, and de novo purine synthesis. The protein consists of two major domains: an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. Mutations in the MTHFD1 gene can lead to methylenetetrahydrofolate dehydrogenase 1 deficiency, characterized by combined immunodeficiency, megaloblastic anemia, and hyperhomocysteinemia.
This enzyme catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate. These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis.
MTHFD1 is also known as CIMAH, MTHFC, MTHFD.
Associated Diseases
- Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
- Neural tube defects, folate-sensitive
