Rare Disease Genes

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Introduction

The ACADVL gene, which stands for acyl-CoA dehydrogenase very long chain, is located on chromosome 17p13.1. It has 20 exons spanning ~5.4kb and encodes a 655 amino acid protein (Very Long-Chain Acyl-CoA Dehydrogenase or VLCAD). VLCAD is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway (1) breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (2). This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids (1). Among the different mitochondrial acyl-CoA dehydrogenases, VLCAD acts specifically on acyl-CoAs with saturated 12 to 24 carbons long primary chains (2).

Predominantly expressed in heart and skeletal muscle also detected in kidney and liver, a deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. The enzyme was found to catalyze the major part of mitochondrial palmitoyl-CoA dehydrogenation in liver, heart, skeletal muscle, and skin fibroblasts (3).

More than 450 unique disease-causing variants in the ACADVL gene have been identified in VLCAD patients and are represented in this database (4). The variants occur across the entire length of the gene and include frameshift, splice site, copy-number, nonsense and missense variants.

Variant List

To see more information, click on the Variant in the table. Hover on the Variant in the table to see its location on the gene. For more information on table headers, HGVS nomenclature, and ACMG classification please use the following links here.

Gene Structure

Show entries

Search by any gene or variant detail to filter the table below:

Variant ID	Variant	Amino Acid Change	Gene Symbol	Variant Type	Effect Type	Display ACMG Call	Disease Subtype	Times Observed	Phenotype	PMID	Location	Present in ClinVar

ACADVL_0001	c.1699_1700delinsTC	p.Arg567Ser	ACADVL	Inversion	Missense	Likely Pathogenic	VLCAD	<5		16183823	Exon 18	No
ACADVL_0002	c.?	p.Met478Ile	ACADVL			Uncertain Significance	VLCAD	<5		35400565		Unknown
ACADVL_0003	c.?	p.Trp249Arg	ACADVL			Uncertain Significance	VLCAD	<5		35400565		Unknown
ACADVL_0006	c.1592G>T	p.Arg531Leu	ACADVL	SNV	Missense	Likely Pathogenic	VLCAD	<5		27209629	Exon 16	No
ACADVL_0007	c.49C>T	p.Leu17Phe	ACADVL	SNV	Missense	Conflict	VLCAD	<5		30445591	Exon 1	Yes
ACADVL_0009	c.1238T>G	p.Ile413Arg	ACADVL	SNV	Missense	Likely Pathogenic	VLCAD	<5		16950999	Exon 12	No
ACADVL_0010	c.1933_1934delinsAA	p.Gly645Asn	ACADVL	Inversion	Missense	Uncertain Significance	VLCAD	<5		16183823	Exon 20	No
ACADVL_0011	c.?	p.Gly354Lys	ACADVL			Uncertain Significance	VLCAD	<5	Abnormality of metabolism/homeostasis, Elevated circulating creatine kinase concentration, Hypoglycemia, Liver abnormality, Myoglobinuria	11596652		Unknown
ACADVL_0012	c.614T>C	p.Leu205Pro	ACADVL	SNV	Missense	Likely Pathogenic	VLCAD	<5		16860141, 16950999	Exon 7	Yes
ACADVL_0013	c.?	p.Gly481Asp	ACADVL			Likely Pathogenic	VLCAD	<5		16950999		Unknown

Showing 1 to 10 of 481 entries

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Column Name	Table View	Detail View
Variant ID
Variant
Amino Acid Change
Gene Symbol
Variant Type
Effect Type
Display ACMG Call
Disease Subtype
Times Observed
Phenotype
PMID
Article Count
Location
Protein Domain
ACMG Call Last Revised Date
GRCh38
Record Last Revised Date
Present in ClinVar
ACMG Call
Predicted ACMG Call
Thousand Genomes Allele Frequency
Ontology Relations
ExAC Allele Frequency
GnomAD Alleles
Associated Geography
Variants Seen With

Notes:

Click the PMID number to go to the corresponding publication.
All variants are referencing NM_000018.3 and NM_000018.4 and there is no change between these versions with respect to the coding sequence.
Genomic coordinates are calculated based on variant data provided: in some cases coordinates are estimated in order to allow users to sort the variants linearly, by approximation.
Click the Present in ClinVar link to go to the corresponding ClinVar VariationID.
Don’t see a variant of interest? Contribute data through the Register Variant form.
Explore considerations about Variants of Uncertain Significance (VUS)

Definition of acronyms:

"*": Referenced a stop codon insertion when listed under amino acid change.
ACMG: American College of Medical Genetics and Genomics
CNV: Copy number variant which here describes a change 100 DNA nucleotides or larger.
SNV: Single DNA nucleotide variant
del: Deletion
dup: Duplication
fs: Frameshift
ins: Insertion

References:

https://www.ncbi.nlm.nih.gov/gene/37
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ACADVL
Aoyama, T. et al., Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients. J Clin Invest. 1995 Jun;95(6):2465-73.
Richbourg et al. Phenotype associations from a comprehensive database of long-chain fatty acid oxidation disorder gene variants (Abstract and poster presentation, ASHG 2023).

Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency ​

Introduction

Variant List

Gene Structure

Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency