ACADVL

Chr 17AR

acyl-CoA dehydrogenase very long chain

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.051 OMIM phenotype
Clinical SummaryACADVL
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Gene-Disease Validity (ClinGen)
very long chain acyl-CoA dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — ACADVL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.000
Z-score 1.32
OE 0.76 (0.561.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.21Z-score
OE missense 1.03 (0.951.12)
390 obs / 378.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.76 (0.561.05)
00.351.4
Missense OE1.03 (0.951.12)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 27 / 35.5Missense obs/exp: 390 / 378.5Syn Z: -1.74
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveACADVL-related very long chain acyl-CoA dehydrogenase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.6442th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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