D2HGDH

Chr 2

D-2-hydroxyglutarate dehydrogenase

Also known as: D2HGD

NCBI Gene: 728294 ENSG00000180902 UniProt: Q8N465

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes D-2hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase type 4 family. This enzyme, which is most active in liver and kidney but also active in heart and brain, converts D-2-hydroxyglutarate to 2-ketoglutarate. Mutations in this gene are present in D-2-hydroxyglutaric aciduria, a rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtD-2-hydroxyglutaric aciduria 1

Clinical highlights

Gene-disease validity (ClinGen)

mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.58

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)