ACADVL

Chr 17

acyl-CoA dehydrogenase very long chain

Also known as: ACAD6, LCACD, VLCAD

NCBI Gene: 37ENSG00000072778UniProt: P49748

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]

Primary Disease Associations & Inheritance

UniProtAcyl-CoA dehydrogenase very long-chain deficiency
181
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ACADVL
🧬
Gene-Disease Validity (ClinGen)
very long chain acyl-CoA dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 80 VUS of 181 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (2)

omim: Error: OMIM fetch failed: 429

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.21Z-score
OE missense 1.03 (0.95–1.12)
390 obs / 378.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.76 (0.56–1.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.95–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 27 / 35.5Missense obs/exp: 390 / 378.5Syn Z: -1.74

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic14
VUS80
Likely Benign70
Conflicting1
16
Pathogenic
14
Likely Pathogenic
80
VUS
70
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
8
0
16
Likely Pathogenic
7
6
1
0
14
VUS
2
60
10
8
80
Likely Benign
0
0
52
18
70
Benign
0
0
0
0
0
Conflicting
—1
Total16677126181

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Gene2Phenotype Curations

ACADVL-related very long chain acyl-CoA dehydrogenase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — ACADVL
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Polydatin Targets ACADVL to Combat Obesity by Promoting Adipocyte Browning and Activating Fatty Acid Oxidation.
He W et al.·Phytother Res
2026
ACADVL upregulation is associated with placental ferroptosis in intrahepatic cholestasis of pregnancy.
Tang M et al.·Biochim Biophys Acta Mol Cell Biol Lipids
2026
Clinical, Biochemical and Molecular Characterisation of Newborns With Fatty Acid β-Oxidation Disorders: Novel Variants in the ACADM , ACADVL and SLC22A5 Genes.
Hidalgo Mayoral I et al.·Clin Genet
2026
Characterization of Variants of Uncertain Significance in ACADVL Gene From a Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency Patient.
Wang Q et al.·Mol Genet Genomic Med
2025🔓 Open Access
ACADVL Deep Sequencing in a Case Study: Beyond the Common c.848T>C Pathogenic Variant.
Baldo F et al.·Genes (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

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

External Resources

Links to major genomics databases and tools