MTHFD2L

Chr 4

methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like

NCBI Gene: 441024 ENSG00000163738 UniProt: Q9H903 OMIM: 614047

This bifunctional mitochondrial enzyme catalyzes methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities in folate metabolism. Mutations cause combined oxidative phosphorylation deficiency 37 with developmental delay, microcephaly, and lactic acidosis through autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (low constraint), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

Multiple*

Mechanism· predicted