ACADVL acyl-CoA dehydrogenase, very long chain [Homo sapiens] - Gene

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Summary

Official Symbol: ACADVLprovided by HGNC
Official Full Name: acyl-CoA dehydrogenase, very long chainprovided by HGNC
Primary source: HGNC:92
See related: Ensembl:ENSG00000072778; HPRD:01940; MIM:609575; Vega:OTTHUMG00000102157
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ACAD6; LCACD; VLCAD
Summary: The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 17p13.1

Sequence :: Chromosome: 17; NC_000017.10 (7123153..7128585)

See ACADVL in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The expressions of LCHAD gene and protein are remarkably reduced in early onset severe preeclampsia and HELLP syndrome.
Title: [Correlation between severe preeclampsia and abnormal expression of long-chain fatty acid oxidative enzyme].
Analyzed potential rhabdomyolysis-susceptibility genes (RYR 1, CPT II, VLCAD and CYP 2D6) from autopsy samples of methamphetamine abusers; no obvious relationship between the genetic mutations observed in this study and rhabdomyolysis was seen.
Title: Genetic analysis of the rhabdomyolysis-associated genes in forensic autopsy cases of methamphetamine abusers.
Down regulation of ACADVL is associated with cervical squamous cell carcinoma.
Title: Differential gene expression identified in Uigur women cervical squamous cell carcinoma by suppression subtractive hybridization.
Missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase is associated with inborn errors of lipid metabolism.
Title: Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.
This study confirms that VLCAD deficiency, although being less frequent than CPT II deficiency, should be systematically considered in the differential diagnosis of exercise-induced rhabdomyolysis.
Title: Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-Coenzyme A dehydrogenase (VLCAD) deficiency.
Results suggest a novel regulatory mechanism for homeostatic VLCAD activity, whose dysregulation might be involved in the production of oxidative stress and in the pathogenesis of idiopathic pulmonary fibrosis.
Title: Dysregulation of very long chain acyl-CoA dehydrogenase coupled with lipid peroxidation.
Observational study of gene-disease association. (HuGE Navigator)
Title: Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.
Loss of heterozygosity on 17p13 and down-regulation of ACADVL can be used to discriminate adrenal cortex neoplasms from adrenocortical adenoma.
Title: Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors.
Bezafibrate, a widely prescribed hypolipidemic drug, cn be used for the correction of VLCAD deficiency and exemplifies the integration of molecular information in a therapeutic strategy
Title: Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.
Report the course of disease in a pair of monozygotic twin sisters.
Title: Very long chain acyl-CoA dehydrogenase deficiency in a pair of mildly affected monozygotic twin sister in their late fifties.

Submit: New GeneRIF Correction See all (13)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD), which catalyzes the initial step of mitochondrial beta-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons, is associated with three phenotypes. The severe early-onset cardiac and multiorgan failure form typically presents in the first months of life with hypertrophic or dilated cardiomyopathy, pericardial effusion, and arrhythmias, as well as hypotonia, hepatomegaly, and intermittent hypoglycemia. The hepatic or hypoketotic hypoglycemic form typically presents during early childhood with hypoketotic hypoglycemia and hepatomegaly, but without cardiomyopathy. The later-onset episodic myopathic form presents with intermittent rhabdomyolysis, muscle cramps and/or pain, and/or exercise intolerance. Hypoglycemia typically is not present at the time of symptoms.

Diagnosis Testing

Diagnosis relies on (1) comprehensive acylcarnitine analysis by tandem mass spectrometry of plasma or a dried blood spot specimen collected during a period of metabolic stress (especially fasting or reduced caloric intake during infectious illness or procedures), followed by (2) molecular genetic testing of ACADVL, the only gene in which mutations are known to cause VLCAD deficiency. Additional diagnostic tests are functional analysis of fatty acid oxidation in cultured fibroblasts and measurement of VLCAD enzyme activity in fibroblasts or lymphocytes.

Genetic Counseling

VLCAD deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

References

PMID: 20301763

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
P49748	P49748	ACADVL	HPRD	PubMed
BioGRID:106555	BioGRID:106555	ACADVL	BioGRID	PubMed	Co-purification
BioGRID:106555	BioGRID:109622	ICT1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106555	BioGRID:114488	SOCS3	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:106555	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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General gene information

Markers

D17S1508E (e-PCR)
- UniSTS:151713

SHGC-35547 (e-PCR)
- UniSTS:15298

RH11576 (e-PCR)
- UniSTS:3310

Genotypes

See ACADVL SNP Geneview Report
See ACADVL SNP Genotype Report
See ACADVL SNP Variation Viewer Report

Homology

Homologs of the ACADVL gene: The ACADVL gene is conserved in chimpanzee, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, and C.elegans.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Activation of Chaperone Genes by XBP1(S), organism-specific biosystem (from REACTOME)
Activation of Chaperone Genes by XBP1(S), organism-specific biosystemXbp-1 (S) binds the sequence CCACG in ER Stress Responsive Elements (ERSE, consensus sequence CCAAT (N)9 CCACG) located upstream from many genes. The ubiquitous transcription factor NF-Y, a heterotri...
Activation of Chaperones by IRE1alpha, organism-specific biosystem (from REACTOME)
Activation of Chaperones by IRE1alpha, organism-specific biosystemIRE1-alpha is a single-pass transmembrane protein that resides in the endoplasmic reticulum (ER) membrane. The C-terminus of IRE1-alpha is located in the cytosol; the N-terminus is located in the ER ...
Beta oxidation of palmitoyl-CoA to myristoyl-CoA, organism-specific biosystem (from REACTOME)
Beta oxidation of palmitoyl-CoA to myristoyl-CoA, organism-specific biosystemThis first pass through the beta-oxidation spiral starts with the saturated fatty acid palmitoyl-CoA and produces myristoyl-CoA. Four enzymatic steps are required, starting with VLCAD CoA dehydrogena...
Diabetes pathways, organism-specific biosystem (from REACTOME)
Diabetes pathways, organism-specific biosystemThis module groups several normal processes that have key roles in the synthesis and function of insulin, insulin-like growth factors and ghrelin, and whose derangement is thus central to the pathoge...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem (from Pathway Interaction Database)
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem
FOXA2 and FOXA3 transcription factor networks
Fatty Acid Beta Oxidation, organism-specific biosystem (from WikiPathways)
Fatty Acid Beta Oxidation, organism-specific biosystemComplete fatty acid beta-oxidation pathway for saturated and unsaturated fatty acids, developed and curated internally by BiGCaT Bioinformatics. This pathway was previously split into three parts p...
Fatty acid metabolism, organism-specific biosystem (from KEGG)
Fatty acid metabolism, organism-specific biosystem
Fatty acid metabolism
Fatty acid metabolism, conserved biosystem (from KEGG)
Fatty acid metabolism, conserved biosystem
Fatty acid metabolism
Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
Mitochondrial Fatty Acid Beta-Oxidation, organism-specific biosystem (from REACTOME)
Mitochondrial Fatty Acid Beta-Oxidation, organism-specific biosystemBeta-oxidation begins once fatty acids have been imported into the mitochondrial matrix by carnitine acyltransferases. The beta-oxidation spiral of fatty acids metabolism involves the repetitive remo...
Mitochondrial LC-Fatty Acid Beta-Oxidation, organism-specific biosystem (from WikiPathways)
Mitochondrial LC-Fatty Acid Beta-Oxidation, organism-specific biosystem
Mitochondrial LC-Fatty Acid Beta-Oxidation
Unfolded Protein Response, organism-specific biosystem (from REACTOME)
Unfolded Protein Response, organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...
beta-Oxidation, organism-specific biosystem (from KEGG)
beta-Oxidation, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Fatty acid metabolism
beta-Oxidation, conserved biosystem (from KEGG)
beta-Oxidation, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Fatty acid metabolism
mitochondrial fatty acid beta-oxidation of saturated fatty acids, organism-specific biosystem (from REACTOME)
mitochondrial fatty acid beta-oxidation of saturated fatty acids, organism-specific biosystemOnce fatty acids have been imported into the mitochondrial matrix by the carnitine acyltransferases, the beta-oxidation spiral begins. Each turn of this spiral concludes with the repetitive removal o...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
acyl-CoA dehydrogenase activity	TAS Traceable Author Statement more info
fatty-acyl-CoA binding	IEA Inferred from Electronic Annotation more info
flavin adenine dinucleotide binding	IEA Inferred from Electronic Annotation more info
long-chain-acyl-CoA dehydrogenase activity	TAS Traceable Author Statement more info	PubMed
very-long-chain-acyl-CoA dehydrogenase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
activation of signaling protein activity involved in unfolded protein response	TAS Traceable Author Statement more info
cellular lipid metabolic process	TAS Traceable Author Statement more info
endoplasmic reticulum unfolded protein response	TAS Traceable Author Statement more info
energy derivation by oxidation of organic compounds	TAS Traceable Author Statement more info	PubMed
fatty acid beta-oxidation	TAS Traceable Author Statement more info
fatty acid beta-oxidation using acyl-CoA dehydrogenase	ISS Inferred from Sequence or Structural Similarity more info
fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
negative regulation of fatty acid biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of fatty acid oxidation	ISS Inferred from Sequence or Structural Similarity more info
regulation of cholesterol metabolic process	ISS Inferred from Sequence or Structural Similarity more info
small molecule metabolic process	TAS Traceable Author Statement more info
temperature homeostasis	ISS Inferred from Sequence or Structural Similarity more info
very long-chain fatty acid catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
membrane	IEA Inferred from Electronic Annotation more info
mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrial nucleoid	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	ISS Inferred from Sequence or Structural Similarity more info

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General protein information

Preferred Names: very long-chain specific acyl-CoA dehydrogenase, mitochondrial

Names: very long-chain specific acyl-CoA dehydrogenase, mitochondrial; acyl-Coenzyme A dehydrogenase, very long chain

NP_000009.1

EC 1.3.99.-

NP_001029031.1

EC 1.3.99.-

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007975.1 RefSeqGene

Range

5001..10433

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000018.2 → NP_000009.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AA643658, AL536186, BC012912, BI822737

Consensus CDS

CCDS11090.1

UniProtKB/Swiss-Prot

P49748

Related

ENSP00000325395, ENST00000322910

Conserved Domains (2) summary

COG1960
Location:94 – 473
Blast Score: 753

CaiA; Acyl-CoA dehydrogenases [Lipid metabolism]

cd01161
Location:72 – 481
Blast Score: 1851

VLCAD; Very long chain acyl-CoA dehydrogenase
NM_001033859.1 → NP_001029031.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in a shorter protein (isoform 2).

Source sequence(s)

AA643658, AL536186, BC020218, BI822737

Consensus CDS

CCDS42249.1

UniProtKB/Swiss-Prot

P49748

Related

ENSP00000344152, ENST00000350303

Conserved Domains (2) summary

COG1960
Location:72 – 451
Blast Score: 751

CaiA; Acyl-CoA dehydrogenases [Lipid metabolism]

cd01161
Location:50 – 459
Blast Score: 1845

VLCAD; Very long chain acyl-CoA dehydrogenase

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

7123153..7128585

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

7015143..7020575

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC120057.9 (173978..179410)	None
genomic	AF244932.1	None
genomic	AJ012053.1	None
genomic	CH471108.2	EAW90246.1
		EAW90247.1
		EAW90248.1
		EAW90249.1
		EAW90250.1
genomic	D78298.2	BAA29057.1
genomic	L46590.1	AAA79002.1
mRNA	AA643658.1	None
mRNA	AK056083.1	BAG51618.1
mRNA	AK056956.1	BAG51833.1
mRNA	AK058109.1	None
mRNA	AK097243.1	None
mRNA	AK222518.1	BAD96238.1
mRNA	AK293537.1	BAG57019.1
mRNA	AK293549.1	BAG57027.1
mRNA	AK302653.1	BAG63892.1
mRNA	AL536186.3	None
mRNA	BC000399.2	AAH00399.1
mRNA	BC012912.1	AAH12912.1
mRNA	BC020218.1	AAH20218.1
mRNA	BI822737.1	None
mRNA	D43682.1	BAA07781.1
mRNA	X86556.1	CAA60253.1