L2HGDH Gene: L-2-Hydroxyglutarate Dehydrogenase
Genetic, structural, and clinical insights into L2HGDH, a mitochondrial enzyme involved in lysine metabolism and linked to L-2-hydroxyglutaric aciduria.
Gene Information Card
| Symbol | L2HGDH |
|---|---|
| Full Name | L-2-hydroxyglutarate dehydrogenase |
| Gene Type | protein-coding |
| Chromosomal Location | 14q21.3 (GRCh38) |
| NCBI Gene ID | 79944 ncbi.nlm.nih.gov/gene/79944 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q9H9P8 |
| OMIM ID | 609584 |
| HGNC ID | 18711 |
| Aliases | C14orf160, DKFZp686O24117, L2HGA |
Description
The L2HGDH gene encodes L-2-hydroxyglutarate dehydrogenase, a mitochondrial FAD-dependent enzyme that catalyzes the conversion of L-2-hydroxyglutarate to alpha-ketoglutarate. This reaction is critical for normal metabolism, and its deficiency leads to the accumulation of L-2-hydroxyglutarate, causing L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder. The gene is located on chromosome 14q21.3 and is expressed in various tissues, with highest levels in the liver, kidney, and brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| L-2-hydroxyglutaric aciduria (L2HGA) | Loss-of-function mutations in L2HGDH impair the conversion of L-2-hydroxyglutarate to alpha-ketoglutarate, leading to toxic accumulation of L-2-hydroxyglutarate in the brain and other tissues. | ClinVar, OMIM (609584), PMID: 15609279 |
| Progressive cerebral atrophy and leukoencephalopathy | Chronic accumulation of L-2-hydroxyglutarate causes neurotoxicity, leading to white matter degeneration and seizures. | OMIM, PMID: 15609279 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Liver | 12.3 | Medium |
| Kidney | 10.1 | Medium |
| Brain (cerebellum) | 8.5 | Medium |
| Heart | 4.2 | Low |
| Skeletal muscle | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (liver) | 15.2 | High expression |
| A549 (lung) | 6.7 | Moderate |
| SH-SY5Y (neuroblastoma) | 5.1 | Moderate |
| MCF7 (breast) | 2.3 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.905C>T (p.Pro302Leu) | Missense | Reported in multiple L2HGA patients | Loss of enzymatic activity |
| c.130C>T (p.Arg44*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1148_1149del (p.Glu383Glyfs*22) | Frameshift | Rare | Frameshift leading to truncated protein |
| c.1A>G (p.Met1?) | Start codon loss | Rare | Loss of translation initiation |
Mutation functional classification
Loss of Function (LOF)
Most L2HGDH mutations are loss-of-function, leading to reduced or absent enzymatic activity, causing L-2-hydroxyglutaric aciduria.
Gain of Function (GOF)
No gain-of-function mutations have been reported for L2HGDH.
Dominant Negative (DN)
No dominant-negative effects have been described; the disorder is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • L-2-hydroxyglutarate dehydrogenase activity |
| • FAD binding | • mitochondrion |
| • alpha-ketoglutarate metabolic process | • L-2-hydroxyglutarate metabolic process |
Pathways
• L-lysine degradation
• 2-hydroxyglutarate metabolism
Protein Summary
L-2-hydroxyglutarate dehydrogenase is a 463-amino acid mitochondrial protein (UniProt Q9H9P8) that belongs to the FAD-dependent oxidoreductase family. It catalyzes the oxidation of L-2-hydroxyglutarate to alpha-ketoglutarate, a key step in lysine metabolism. The protein is expressed in mitochondria and is critical for preventing toxic accumulation of L-2-hydroxyglutarate. Mutations causing loss of function lead to L-2-hydroxyglutaric aciduria, characterized by progressive neurological symptoms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| L2HGDH Knockout HEK293 Cell Line | EDJ-KQ14021 | Human | 79944 | Details Get a Quote |
| L2HGDH Knockout A-549 Cell Line | EDJ-KQ43926 | Human | 79944 | Details Get a Quote |
| L2HGDH Knockout HCT 116 Cell Line | EDJ-KQ43927 | Human | 79944 | Details Get a Quote |
| L2HGDH Knockout HeLa Cell Line | EDJ-KQ43928 | Human | 79944 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
