D2HGDH
Chr 2ARD-2-hydroxyglutarate dehydrogenase
Also known as: D2HGD
This mitochondrial enzyme catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate and is most active in liver and kidney but also functions in heart and brain. Mutations cause D-2-hydroxyglutaric aciduria, an autosomal recessive neurometabolic disorder presenting with developmental delay, epilepsy, hypotonia, and dysmorphic features. The gene is highly constrained against loss-of-function variants (LOEUF 0.58), reflecting its essential metabolic role.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
D2HGDH · 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