IVD Gene - Isovaleryl-CoA Dehydrogenase
IVD: A key enzyme in leucine catabolism, associated with isovaleric acidemia
Gene Information Card
| Symbol | IVD |
|---|---|
| Full Name | Isovaleryl-CoA Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 3712 ncbi.nlm.nih.gov/gene/3712 |
| Ensembl ID | ENSG00000128928 |
| UniProt ID | P26440 |
| OMIM ID | 607036 |
| HGNC ID | 6186 |
| Aliases | ACAD2, IVDH, isovaleryl coenzyme A dehydrogenase |
Description
The IVD gene encodes isovaleryl-CoA dehydrogenase, a mitochondrial enzyme that catalyzes the third step in leucine catabolism, converting isovaleryl-CoA to 3-methylcrotonyl-CoA. Mutations in IVD cause isovaleric acidemia, an autosomal recessive disorder of organic acid metabolism characterized by accumulation of isovaleric acid and its derivatives.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Isovaleric acidemia | Loss-of-function mutations in IVD impair isovaleryl-CoA dehydrogenase activity, leading to accumulation of isovaleryl-CoA and its toxic metabolites. | ClinVar, OMIM |
| Multiple acyl-CoA dehydrogenase deficiency (MADD) | Secondary involvement; IVD activity may be reduced due to defects in electron transfer flavoprotein (ETF) or ETF dehydrogenase, but primary IVD mutations are not causative. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Medium |
| Skeletal muscle | 5.4 | Medium |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | High expression in liver-derived cell line |
| HEK293 | 4.5 | Moderate expression |
| K562 | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.149G>A (p.Arg50Gln) | Missense | Common in isovaleric acidemia | Reduced enzyme activity |
| c.1208A>G (p.Tyr403Cys) | Missense | Rare | Impaired substrate binding |
| c.457C>T (p.Arg153Trp) | Missense | Reported | Loss of function |
| c.1180C>T (p.Arg394Trp) | Missense | Reported | Decreased stability and activity |
Mutation functional classification
Loss of Function (LOF)
Most IVD mutations are loss-of-function, reducing or abolishing isovaleryl-CoA dehydrogenase activity, leading to isovaleric acidemia.
Gain of Function (GOF)
No gain-of-function mutations reported for IVD.
Dominant Negative (DN)
No dominant-negative effects described; isovaleric acidemia is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Valine
• leucine and isoleucine degradation (KEGG: hsa00280)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
Protein Summary
Isovaleryl-CoA dehydrogenase (IVD) is a homotetrameric mitochondrial flavoprotein that catalyzes the oxidative decarboxylation of isovaleryl-CoA to 3-methylcrotonyl-CoA, using FAD as a cofactor. The enzyme is essential for leucine catabolism. Defects in IVD cause isovaleric acidemia, characterized by vomiting, metabolic acidosis, and neurological impairment. The protein is expressed predominantly in liver and kidney.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IVD Knockout HEK293 Cell Line | EDJ-KQ5012 | Human | 3712 | Details Get a Quote |
| IVD Knockout A-549 Cell Line | EDJ-KQ27924 | Human | 3712 | Details Get a Quote |
| IVD Knockout HCT 116 Cell Line | EDJ-KQ27925 | Human | 3712 | Details Get a Quote |
| IVD Knockout HeLa Cell Line | EDJ-KQ27926 | Human | 3712 | Details Get a Quote |
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