acyl-CoA dehydrogenase very long chain
Annotations refreshed 1 month ago.
Diagnostic Grade (Green)
Acute rhabdomyolysis
BIALLELIC, autosomal or pseudoautosomalDDG2P
BIALLELIC, autosomal or pseudoautosomalFetal anomalies
BIALLELIC, autosomal or pseudoautosomalHyperammonaemia
BIALLELIC, autosomal or pseudoautosomalLikely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomalLimb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
BIALLELIC, autosomal or pseudoautosomalPaediatric or syndromic cardiomyopathy
BIALLELIC, autosomal or pseudoautosomalRhabdomyolysis and metabolic muscle disorders
BIALLELIC, autosomal or pseudoautosomal+7 more panels — install the extension to see the full list inline on any page.
very long chain acyl-CoA dehydrogenase deficiency
hereditary disease
long chain acyl-CoA dehydrogenase deficiency
rhabdomyolysis
Acute rhabdomyolysis
Abnormal circulating enzyme concentration
metabolic myopathy
Abnormality of the musculature
cardiac arrhythmia
myopathy
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Very long-chain acyl-CoA dehydrogenase, mitochondrial
Catalyzes the first of the four reactions of the mitochondrial fatty acid beta-oxidation (FAO) pathway, which consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:17564966, PubMed:18227065, PubMed:26474213, PubMed:7668252, PubMed:9461620, PubMed:9599005, PubMed:9839948). The mitochondrial FAO pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions (PubMed:26474213, PubMed:7668252). Each FAO cycle shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA (for the citric acid cycle), one FADH(2), and one NADH (which donate electrons to the respiratory chain for ATP production) (PubMed:26474213, PubMed:7668252). Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on fatty acyl-CoAs with saturated 12 to 24 carbons long primary chains (PubMed:17564966, PubMed:21237683, PubMed:9839948), but can also catalyze monounsaturated fatty acids such as oleate ((9Z)-octadecenoate), (9Z)-hexadecenoate, and others (PubMed:17564966). Can use (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate as substrate in vitro (which is not primarily used for energy but mainly beta-oxidized in the peroxisomes) (PubMed:17564966, PubMed:26474213). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on substrates that have not been tested experimentally but are metabolized by mitochondrial FAO, including long-chain unsaturated fatty acids such as linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others (PubMed:26474213). Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACAD9 and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the heart and skeletal muscle (PubMed:17564966)
ACADVL · P49748
Mean pLDDT
90.3/ 100
Very high
655 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
