L2HGDH
Chr 14ARL-2-hydroxyglutarate dehydrogenase
Also known as: C14orf160, L2HGA
L-2-hydroxyglutarate dehydrogenase is a FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in mammalian tissues. Mutations cause L-2-hydroxyglutaric aciduria, an autosomal recessive neurometabolic disorder resulting in moderate to severe cognitive disability. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.787), indicating intolerance to protein-disrupting mutations.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
L2HGDH · 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