GCDH Gene - Glutaryl-CoA Dehydrogenase
Genetic and functional insights into GCDH, associated with glutaric acidemia type I
Gene Information Card
| Symbol | GCDH |
|---|---|
| Full Name | Glutaryl-CoA Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.13 |
| NCBI Gene ID | 2639 ncbi.nlm.nih.gov/gene/2639 |
| Ensembl ID | ENSG00000105607 |
| UniProt ID | Q92947 |
| OMIM ID | 608801 |
| HGNC ID | 4189 |
| Aliases | ACAD5, GCD |
Description
The GCDH gene encodes glutaryl-CoA dehydrogenase, a mitochondrial enzyme involved in the catabolism of lysine, hydroxylysine, and tryptophan. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO2. Mutations in GCDH cause glutaric acidemia type I (GA1), an autosomal recessive disorder characterized by accumulation of glutaric acid and neurological damage.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glutaric acidemia type I (GA1) | Loss-of-function mutations impair glutaryl-CoA dehydrogenase activity, leading to accumulation of glutaric acid and 3-hydroxyglutaric acid, causing striatal injury and encephalopathic crises. | ClinVar, OMIM |
| Multiple acyl-CoA dehydrogenase deficiency (MADD) | Secondary deficiency due to electron transfer flavoprotein defects; GCDH activity is indirectly affected. | OMIM |
| Glutaric aciduria type I | Same as GA1; alternative nomenclature. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.2 | Medium |
| Brain | 6.1 | Medium |
| Heart | 5.8 | Medium |
| Skeletal muscle | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Hepatocyte-derived, high expression |
| HEK293 | 7.4 | Embryonic kidney, moderate expression |
| SH-SY5Y | 5.9 | Neuroblastoma, moderate expression |
| K562 | 3.2 | Leukemia, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1240C>T (p.Arg414Trp) | Missense | Common in European populations | Loss of function, reduced enzyme activity |
| c.1204C>T (p.Arg402Trp) | Missense | Found in GA1 patients | Loss of function |
| c.914C>T (p.Thr305Met) | Missense | Reported in multiple ethnic groups | Loss of function |
| c.1240C>A (p.Arg414Ser) | Missense | Rare | Loss of function |
| c.1150G>A (p.Gly384Arg) | Missense | Reported in GA1 | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most GCDH mutations are loss-of-function, reducing or abolishing enzyme activity, leading to glutaric acidemia type I.
Gain of Function (GOF)
No gain-of-function mutations reported for GCDH.
Dominant Negative (DN)
No dominant-negative mutations reported; GA1 is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Lysine degradation (KEGG: hsa00310)
• Tryptophan metabolism (KEGG: hsa00380)
• Fatty acid degradation (KEGG: hsa00071)
Protein Summary
Glutaryl-CoA dehydrogenase (GCDH) is a 438-amino acid mitochondrial flavoprotein that forms a homotetramer. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA, a key step in the catabolism of lysine, hydroxylysine, and tryptophan. The enzyme requires FAD as a cofactor. Deficiency leads to glutaric acidemia type I, with accumulation of neurotoxic metabolites.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCDH Knockout HEK293 Cell Line | EDJ-KQ4688 | Human | 2639 | Details Get a Quote |
| GCDH Knockout A-549 Cell Line | EDJ-KQ26152 | Human | 2639 | Details Get a Quote |
| GCDH Knockout HCT 116 Cell Line | EDJ-KQ27394 | Human | 2639 | Details Get a Quote |
| GCDH Knockout HeLa Cell Line | EDJ-KQ27395 | Human | 2639 | Details Get a Quote |
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