D2HGDH Gene (D-2-Hydroxyglutarate Dehydrogenase)
Mitochondrial enzyme involved in D-2-hydroxyglutarate metabolism and linked to D-2-hydroxyglutaric aciduria
Gene Information Card
| Symbol | D2HGDH |
|---|---|
| Full Name | D-2-hydroxyglutarate dehydrogenase |
| Gene Type | protein-coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 728294 ncbi.nlm.nih.gov/gene/728294 |
| Ensembl ID | ENSG00000138079 |
| UniProt ID | Q8N465 |
| OMIM ID | 609186 |
| HGNC ID | 28358 |
| Aliases | D2HGD, D-2-HGDH, FLJ12713 |
Description
The D2HGDH gene encodes D-2-hydroxyglutarate dehydrogenase, a mitochondrial enzyme that catalyzes the conversion of D-2-hydroxyglutarate (D-2-HG) to alpha-ketoglutarate. This reaction is critical for preventing the accumulation of D-2-HG, a metabolite that can disrupt cellular metabolism and promote tumorigenesis. Mutations in D2HGDH cause D-2-hydroxyglutaric aciduria, a neurometabolic disorder characterized by elevated D-2-HG levels in body fluids.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| D-2-hydroxyglutaric aciduria | Loss-of-function mutations in D2HGDH impair D-2-HG catabolism, leading to toxic accumulation of D-2-HG in the brain and other tissues. | OMIM #600721; multiple case reports and functional studies |
| Metabolic encephalopathy | Secondary to D-2-HG accumulation, causing neurological symptoms such as seizures, developmental delay, and hypotonia. | ClinVar; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 6.7 | Low |
| Heart | 5.1 | Low |
| Skeletal Muscle | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 9.8 | Moderate expression |
| HepG2 | 7.4 | Low expression |
| SH-SY5Y | 11.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.905G>A (p.Arg302His) | Missense | Rare | Loss of function; associated with D-2-hydroxyglutaric aciduria |
| c.1124T>C (p.Leu375Pro) | Missense | Rare | Loss of function; reduced enzyme activity |
| c.1291C>T (p.Arg431*) | Nonsense | Rare | Loss of function; premature truncation |
Mutation functional classification
Loss of Function (LOF)
Most reported D2HGDH mutations are loss-of-function, leading to reduced or absent enzyme activity and D-2-HG accumulation.
Gain of Function (GOF)
No gain-of-function mutations have been described for D2HGDH.
Dominant Negative (DN)
No dominant-negative effects have been reported; the disorder follows an autosomal recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • D-2-hydroxyglutarate dehydrogenase activity (GO:0008670) |
| • 2-oxoglutarate metabolic process (GO:0006103) | • glyoxylate metabolic process (GO:0046487) |
Pathways
• D-2-hydroxyglutarate degradation (Reactome: R-HSA-389661)
• Metabolism of alpha-ketoglutarate (KEGG: hsa00280)
Protein Summary
D-2-hydroxyglutarate dehydrogenase is a 521-amino acid mitochondrial protein that belongs to the FAD-dependent oxidoreductase family. It catalyzes the reversible oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate, using FAD as a cofactor. The enzyme is essential for clearing D-2-HG, an oncometabolite that inhibits alpha-ketoglutarate-dependent dioxygenases. Deficiency leads to D-2-hydroxyglutaric aciduria and may contribute to cancer progression when D-2-HG levels are elevated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| D2HGDH Knockout HEK293 Cell Line | EDJ-KQ13090 | Human | 728294 | Details Get a Quote |
| D2HGDH Knockout A-549 Cell Line | EDJ-KQ42377 | Human | 728294 | Details Get a Quote |
| D2HGDH Knockout HCT 116 Cell Line | EDJ-KQ42378 | Human | 728294 | Details Get a Quote |
| D2HGDH Knockout HeLa Cell Line | EDJ-KQ42379 | Human | 728294 | Details Get a Quote |
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