Methenyltetrahydrofolate Synthetase Domain Containing Protein (MTHFSD)

Methenyltetrahydrofolate synthetase (EC 6.3.3.2) catalyzes the irreversible ATP and Mg2+-dependent transformation of 5-formyltetrahydrofolate (N5-HCO-H4-pteroylglutamic acid (PteGlu] to 5,10-methenyltetrahydrofolate. Methenyltetrahydrofolate synthetase (MTHFS) is the only enzyme that metabolizes 5-formylTHF and catalyzes its ATP-dependent conversion to 5,10-methenylTHF. This reaction determines intracellular 5-formylTHF concentrations and converts 5-formylTHF into an enzyme cofactor. Patients with deletions spanning the entire FOX cluster (FOXF1, MTHFSD, FOXC2 and FOXL1) at 16q24.1 have, in addition to ACD/MPV, esophageal atresia, tracheo-esophageal fistula, and other gastro-intestinal tract atresias. Mutations in MTHFSD and FOXL1 have not been described in humans.