DHFR2
Chr 3dihydrofolate reductase 2
Also known as: DHFRL1, DHFRP4
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
DHFR2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools