DHFR2

Chr 3

dihydrofolate reductase 2

Also known as: DHFRL1, DHFRP4

NCBI Gene: 200895 ENSG00000178700 UniProt: Q86XF0 OMIM: 616588

The protein is a key enzyme in mitochondrial folate metabolism that catalyzes dihydrofolate reduction and contributes to thymidylate biosynthesis, preventing uracil accumulation in mitochondrial DNA. Mutations cause autosomal recessive mitochondrial DNA depletion syndrome, which typically presents in infancy with severe neurological deterioration, developmental delays, and multi-organ dysfunction. The gene shows moderate tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

Enables dihydrofolate reductase activity and mRNA binding activity. Involved in tetrahydrofolate metabolic process and thymidine biosynthetic process. Located in mitochondrial inner membrane and mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

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P/LP missense

1.44

LOEUF

Mechanism· predicted