ACADL

Chr 2

acyl-CoA dehydrogenase long chain

Also known as: ACAD4, LCAD

NCBI Gene: 33ENSG00000115361UniProt: P28330

The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

118
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ACADL
🧬
Gene-Disease Validity (ClinGen)
long chain acyl-CoA dehydrogenase deficiency · ARDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 70 VUS of 118 total submissions

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.
1.16LOEUF
pLI 0.000
Z-score 0.91
OE 0.81 (0.57–1.16)
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.
0.86Z-score
OE missense 0.84 (0.75–0.95)
196 obs / 232.7 exp
Tolerant

Mild missense constraint

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.0.81 (0.57–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.75–0.95)
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.0.75
0≤1.21.6
LoF obs/exp: 21 / 26.0Missense obs/exp: 196 / 232.7Syn Z: 1.79

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
VUS70
Likely Benign16
Benign6
Conflicting3
23
Pathogenic
70
VUS
16
Likely Benign
6
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
0
0
0
VUS
2
61
7
0
70
Likely Benign
1
3
5
7
16
Benign
0
2
2
2
6
Conflicting
—3
Total366379118

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

View in ClinVar →

Protein Context — Lollipop Plot

ACADL · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma.
Cai J et al.·Int J Biol Sci
2023
HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing.
Yang J et al.·Int J Nanomedicine
2024
Refining prognostic stratification of atypical meningiomas: significance of chromosome 1p deletion and brain invasion.
Zanconato G et al.·Acta Neuropathol Commun
2025
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
Roberts JL et al.·Gene
2014
A gene therapy targeting medium-chain acyl-CoA dehydrogenase (MCAD) did not protect against diabetes-induced cardiac pathology.
Weeks KL et al.·J Mol Med (Berl)
2024
A Prognostic Model Based on Six Metabolism-Related Genes in Colorectal Cancer.
Sun YL et al.·Biomed Res Int
2020Functional
Comprehensive Analysis of Alteration Landscape and Its Clinical Significance of Mitochondrial Energy Metabolism Pathway-Related Genes in Lung Cancers.
Ye Z et al.·Oxid Med Cell Longev
2021
Identification and Verification of Hub Mitochondrial Dysfunction Genes in Osteoarthritis Based on Bioinformatics Analysis.
Niu H et al.·J Immunol Res
2024
Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma.
Zhang J et al.·Sci Rep
2015
Integrated analysis of gene expression and methylation profiles of 48 candidate genes in breast cancer patients.
Li Z et al.·Breast Cancer Res Treat
2016Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Prognostic significance of ACADL and MCM2 in meningiomas: Current evidence and clinical implications.
Pietrantoni A et al.·Histol Histopathol
2026
ACADL and ADH1B signify ketone body metabolic reprogramming in osteoarthritic synovium: insights from bioinformatics and animal model studies.
Li K et al.·Front Med (Lausanne)
2026🔓 Open AccessFunctional
Integrated transcriptomic analysis and experimental validation identify ACADL as a mitochondrial tumor suppressor via the FOXO3a/PUMA axis in lung adenocarcinoma.
Wang Y et al.·Eur J Med Res
2026🔓 Open Access
EBF3 transcriptionally activates ACADL to block the Hippo/YAP signaling pathway and inhibits breast cancer progression.
Cao C et al.·Pathol Res Pract
2026
Retraction: ACADL functions as a tumor suppressor in hepatocellular carcinoma metastasis by inhibiting matrix metalloproteinase 14.
Frontiers Editorial Office.·Front Oncol
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools