ACADVL acyl-CoA dehydrogenase very long chain [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACADVLprovided by HGNC
Official Full Name: acyl-CoA dehydrogenase very long chainprovided by HGNC
Primary source: HGNC:HGNC:92
See related: Ensembl:ENSG00000072778 MIM:609575
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]
Expression: Ubiquitous expression in adrenal (RPKM 228.7), duodenum (RPKM 185.5) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 17p13.1

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	17	NC_000017.11 (7217125..7225267)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (7120444..7128586)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

There are currently no biochemical markers for prediction of disease severity and for the need for treatment in VLCAD deficiency. Mutation analysis may offer predictive value but this may not be robust enough for a large proportion of those mutations that have not been previously reported in clinically affected patients.
Title: VLCAD deficiency: Follow-up and outcome of patients diagnosed through newborn screening in Victoria.
We retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by NBS and describe initial presentations, diagnosis, clinical outcomes and treatment in a cohort of 52 individuals ages 1-18year.
Title: Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.
LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy.
Title: Tissue specific expression of human fatty acid oxidation enzyme genes in late pregnancy.
following variants should be considered likely pathogenic c.1273G > A (p.A425T), c.1001T > G (p.M334R), c.538G > A (p.A180T), c.640T > G (p.F214V), c.1076C > T (p.A359V), c.1019G > T (p.G340V), c.889_891delGAG (p.E297del), and c.1103A > C (p.Q368P); patients homozygous for the most common pathogenic variant, c.848T > C (p.V283A) can be expected to have a more benign clinical course
Title: Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States.
11 mutations in ACADVL gene in 7 patients, 7 reported (p.S22X, p.W427X, p.A213T, p.G222R, p.R450H, c.296-297delCA, c.1605+1G>T), 4 novel (p.S72F, p.Q100X, p.M437T, p.D466Y). p.R450H and p.D466Y (14.28%, 2/14 alleles) mutations identified in 2 alleles.
Title: Clinical features and mutations in seven Chinese patients with very long chain acyl-CoA dehydrogenase deficiency.
Case Report: missense mutation within the ACADVL gene responsible for very-long-chain acyl-CoA dehydrogenase deficiency and sudden infant death.
Title: Genotype-phenotype correlations: sudden death in an infant with very-long-chain acyl-CoA dehydrogenase deficiency.
These results emphasize the importance of functional investigation of abnormal NBS or clinical testing suggestive but not diagnostic of very-long-chain acyl-CoA dehydrogenase .
Title: Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency.
These findings support the importance of considering that mutations may be present in the ACADVL gene when a significant partial deficiency is found in CPTII activity, but no mutations in the CPT2 gene can be identified.
Title: Novel mutations in the gene encoding very long-chain acyl-CoA dehydrogenase identified in patients with partial carnitine palmitoyltransferase II deficiency.
Identification of 2 VLCAD mutations leads to precautions in the management of the children with VLCAD deficiency.
Title: VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment.
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].

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Very long chain acyl-CoA dehydrogenase deficiency MedGen: C3887523 OMIM: 201475 GeneReviews: Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

Go to the top of the page Help

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...
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 degradation, organism-specific biosystem (from KEGG)
Fatty acid degradation, organism-specific biosystem
Fatty acid degradation
Fatty acid degradation, conserved biosystem (from KEGG)
Fatty acid degradation, conserved biosystem
Fatty acid degradation
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...
IRE1alpha activates chaperones, organism-specific biosystem (from REACTOME)
IRE1alpha activates chaperones, 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 ...
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...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
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 (UPR), organism-specific biosystem (from REACTOME)
Unfolded Protein Response (UPR), 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...
XBP1(S) activates chaperone genes, organism-specific biosystem (from REACTOME)
XBP1(S) activates chaperone genes, 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...
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...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D17S1508E (e-PCR)
- UniSTS:151713

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

RH11576 (e-PCR)
- UniSTS:3310

Homology

Homologs of the ACADVL gene: The ACADVL gene is conserved in chimpanzee, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, and C.elegans.
Orthologs from Annotation Pipeline: 200 organisms have orthologs with human gene ACADVL
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
fatty-acyl-CoA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
flavin adenine dinucleotide binding	IEA Inferred from Electronic Annotation more info
long-chain-acyl-CoA dehydrogenase activity	IDA Inferred from Direct Assay more info	PubMed
very-long-chain-acyl-CoA dehydrogenase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
IRE1-mediated unfolded protein response	TAS Traceable Author Statement more info
energy derivation by oxidation of organic compounds	TAS Traceable Author Statement more info	PubMed
epithelial cell differentiation	IEP Inferred from Expression Pattern more info	PubMed
fatty acid beta-oxidation	TAS Traceable Author Statement more info
fatty acid beta-oxidation using acyl-CoA dehydrogenase	IDA Inferred from Direct Assay more info	PubMed
fatty acid beta-oxidation using acyl-CoA dehydrogenase	ISS Inferred from Sequence or Structural Similarity 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
response to cold	IEA Inferred from Electronic Annotation more info
temperature homeostasis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
cytosol	IDA Inferred from Direct Assay more info
mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrial membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrial nucleoid	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info
mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
nucleolus	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info

General protein information

Go to the top of the page Help

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

Names: acyl-Coenzyme A dehydrogenase, very long chain

NP_000009.1

EC 1.3.8.9

NP_001029031.1

EC 1.3.8.9

NP_001257376.1

EC 1.3.8.9

NP_001257377.1

EC 1.3.8.9

XP_006721579.2

EC 1.3.8.9

XP_011522131.1

EC 1.3.8.9

XP_011522132.1

EC 1.3.8.9

XP_024306509.1

EC 1.3.8.9

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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

4998..10434

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000018.4 → NP_000009.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_000009.1

Status: REVIEWED

Description

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

Source sequence(s)

BC000399

Consensus CDS

CCDS11090.1

UniProtKB/Swiss-Prot

P49748

Related

ENSP00000349297.5, ENST00000356839.9

Conserved Domains (1) summary

cd01161
Location:72 → 481

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

See identical proteins and their annotated locations for NP_001029031.1

Status: REVIEWED

Description

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

Source sequence(s)

BC020218, BP387474, DA945553

Consensus CDS

CCDS42249.1

UniProtKB/Swiss-Prot

P49748

Related

ENSP00000344152.5, ENST00000350303.9

Conserved Domains (2) summary

cd01161
Location:50 → 459

VLCAD; Very long chain acyl-CoA dehydrogenase

COG1960
Location:80 → 451

CaiA; Acyl-CoA dehydrogenase related to the alkylation response protein AidB [Lipid transport and metabolism]
NM_001270447.1 → NP_001257376.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (3) is longer and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC120057, AK293549, BC000399, BP387474

Consensus CDS

CCDS58509.1

UniProtKB/Swiss-Prot

P49748

Related

ENSP00000438689.2, ENST00000543245.6

Conserved Domains (2) summary

cd01161
Location:95 → 504

VLCAD; Very long chain acyl-CoA dehydrogenase

COG1960
Location:125 → 496

CaiA; Acyl-CoA dehydrogenase related to the alkylation response protein AidB [Lipid transport and metabolism]
NM_001270448.1 → NP_001257377.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform 4

See identical proteins and their annotated locations for NP_001257377.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an additional segment in the 5' exon, compared to variant 1. The 5'-most supported initiation codon, as used in variant 1, is associated with a weak Kozak sequence and a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG, and result in an isoform (4), which is shorter at the N-terminus, compared to isoform 1.

Source sequence(s)

AK056083, BI822737, BP387474, DA945553

UniProtKB/TrEMBL

B3KPA6

Conserved Domains (2) summary

cd01161
Location:1 → 405

VLCAD; Very long chain acyl-CoA dehydrogenase

COG1960
Location:26 → 397

CaiA; Acyl-CoA dehydrogenase related to the alkylation response protein AidB [Lipid transport and metabolism]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p12 Primary Assembly

Range

7217125..7225267

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006721516.3 → XP_006721579.2 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform X1

Conserved Domains (2) summary

cd01161
Location:72 → 481

VLCAD; Very long chain acyl-CoA dehydrogenase

COG1960
Location:102 → 473

CaiA; Acyl-CoA dehydrogenase related to the alkylation response protein AidB [Lipid transport and metabolism]
XM_024450741.1 → XP_024306509.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform X2

Conserved Domains (1) summary

cd01161
Location:72 → 478

VLCAD; Very long chain acyl-CoA dehydrogenase
XM_011523830.2 → XP_011522132.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform X4

Conserved Domains (2) summary

cd01161
Location:72 → 478

VLCAD; Very long chain acyl-CoA dehydrogenase

COG1960
Location:102 → 473

CaiA; Acyl-CoA dehydrogenase related to the alkylation response protein AidB [Lipid transport and metabolism]
XM_011523829.2 → XP_011522131.1 very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform X3

Conserved Domains (2) summary

cd01161
Location:72 → 478

VLCAD; Very long chain acyl-CoA dehydrogenase

COG1960
Location:102 → 473

CaiA; Acyl-CoA dehydrogenase related to the alkylation response protein AidB [Lipid transport and metabolism]