MTHFD2L Gene: Function, Expression, and Disease Associations | Biomedical Database

MTHFD2L encodes a mitochondrial enzyme that catalyzes the interconversion of folate derivatives, specifically the NADP+-dependent oxidation of methylenetetrahydrofolate to methenyltetrahydrofolate and the subsequent hydrolysis to formyltetrahydrofolate. This enzyme is part of the mitochondrial folate one-carbon metabolism pathway, which is essential for purine and thymidylate synthesis, amino acid metabolism, and redox homeostasis. MTHFD2L is expressed in various tissues and is upregulated in certain cancers, suggesting a role in tumor metabolism.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Folate metabolism (mitochondrial one-carbon pool)

• Glycine

• serine and threonine metabolism

• Purine metabolism (indirect via one-carbon units)

MTHFD2L is a 350-amino acid mitochondrial protein with bifunctional enzymatic activity: it acts as a methylenetetrahydrofolate dehydrogenase (NADP+) and a methenyltetrahydrofolate cyclohydrolase. The protein is localized in the mitochondrial matrix and is involved in the conversion of 5,10-methylenetetrahydrofolate to 10-formyltetrahydrofolate, which is used for de novo purine synthesis and formylmethionyl-tRNA formation. MTHFD2L shares sequence similarity with MTHFD2 but is distinct in its tissue distribution and regulation. It is expressed at low levels in most normal tissues but is upregulated in several cancer types, suggesting a role in tumor metabolism. The protein structure includes an N-terminal mitochondrial targeting sequence and a catalytic domain. Post-translational modifications and interacting partners are not well characterized.