ACADVL

Chr 17AR

acyl-CoA dehydrogenase very long chain

Also known as: ACAD6, LCACD, VLCAD

NCBI Gene: 37 ENSG00000072778 UniProt: P49748 OMIM: 609575

The protein catalyzes the first step of mitochondrial fatty acid beta-oxidation, specifically dehydrogenating very long-chain fatty acyl-CoAs (12-24 carbons) to produce energy from fats. Autosomal recessive mutations cause VLCAD deficiency, which presents with cardiomyopathy due to reduced myocardial fatty acid beta-oxidation. The pathogenic mechanism involves loss of function mutations that impair the enzyme's ability to break down long-chain fatty acids.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

VLCAD deficiencyMIM #201475

UniProtAcyl-CoA dehydrogenase very long-chain deficiency

Clinical highlights

Gene-disease validity (ClinGen)

very long chain acyl-CoA dehydrogenase deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ACADVL

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.32

OE 0.76 (0.56–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.03 (0.95–1.12)

390 obs / 378.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.56–1.05)

0≤0.351.4

Missense OE?1.03 (0.95–1.12)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 27 / 35.5Missense obs/exp: 390 / 378.5Syn Z: -1.74

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ACADVL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — ACADVL

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Mitochondrial DiseasesPearson Syndrome

Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)

RECRUITING

NCT06017869Phase PHASE2Minovia Therapeutics Ltd.Started 2023-07-31

MNV-201

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Biochemical and molecular characteristics among infants with abnormal newborn screen for very-long-chain acyl-CoA dehydrogenase deficiency: A single center experience

Upadia J et al.·Mol Genet Metab Rep

2023