ACOX1

Chr 17ADAR

acyl-CoA oxidase 1

Also known as: ACOX, AOX, MITCH, PALMCOX, SCOX

NCBI Gene: 51ENSG00000161533UniProt: Q15067

The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Mitchell syndromeMIM #618960
AD
Peroxisomal acyl-CoA oxidase deficiencyMIM #264470
AR
UniProtAdrenoleukodystrophy, pseudoneonatal
452
ClinVar variants
42
Pathogenic / LP
0.06
pLI score
1
Active trials
Clinical Summary— ACOX1
🧬
Gene-Disease Validity (ClinGen)
peroxisomal acyl-CoA oxidase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 178 VUS of 452 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.062
Z-score 3.97
OE 0.26 (0.16–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.98Z-score
OE missense 0.71 (0.64–0.79)
258 obs / 364.5 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.0.26 (0.16–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.64–0.79)
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.0.98
0≤1.21.6
LoF obs/exp: 9 / 34.0Missense obs/exp: 258 / 364.5Syn Z: 0.22

ClinVar Variant Classifications

452 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic15
VUS178
Likely Benign190
Benign37
Conflicting5
27
Pathogenic
15
Likely Pathogenic
178
VUS
190
Likely Benign
37
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
3
20
0
27
Likely Pathogenic
9
1
5
0
15
VUS
1
120
50
7
178
Likely Benign
0
3
72
115
190
Benign
0
1
35
1
37
Conflicting
—5
Total14128182123452

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

View in ClinVar →

Protein Context — Lollipop Plot

ACOX1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ACOX1-related adrenoleukodystrophy pseudoneonatal

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitchell syndrome

MIM #618960

Molecular basis of disorder known

Autosomal dominant

Peroxisomal acyl-CoA oxidase deficiency

MIM #264470

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data.
Zhao S et al.·Funct Integr Genomics
2024
Shenge Formula attenuates high-fat diet-induced obesity and fatty liver via inhibiting ACOX1.
Shang Z et al.·Phytomedicine
2024
CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARα pathways.
Li J et al.·J Hepatol
2015
ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia.
Tannoury M et al.·Leukemia
2024
A de novo heterozygous variant in ACOX1 gene cause Mitchell syndrome: the first case in China and literature review.
Shen M et al.·BMC Med Genomics
2023Review
Huangqi and Danshen improve the chronic nephrotoxicity of cyclosporin A by regulating lipid metabolism.
Gao RR et al.·Phytomedicine
2025
CLIC1 regulates cellular oxidative stress and gastric cancer progress by enhancing ACOX1 ubiquitination.
Li C et al.·Int J Biol Macromol
2025
Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms.
Chung HL et al.·Neuron
2020Functional
Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.
Helvacioglu D et al.·Eur J Endocrinol
2025Case report
Anti-Obesity Properties of a Novel Probiotic Strain of Latilactobacillus sakei CNTA 173 in Caenorhabditis elegans.
Goyache I et al.·Int J Mol Sci
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Peroxisome Biogenesis DisorderZellweger Spectrum DisorderRCDP - Rhizomelic Chondrodysplasia Punctata

Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

RECRUITING
NCT01668186McGill University Health Centre/Research Institute of the McGill University Health CentreStarted 2012-01

External Resources

Links to major genomics databases and tools