ACOX1

Chr 17ADAR

acyl-CoA oxidase 1

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

The protein catalyzes the first step of peroxisomal fatty acid beta-oxidation, converting acyl-CoAs to 2-trans-enoyl-CoAs while producing hydrogen peroxide. Mutations cause peroxisomal acyl-CoA oxidase deficiency and Mitchell syndrome through both autosomal recessive loss-of-function and autosomal dominant gain-of-function mechanisms, leading to accumulation of very long chain fatty acids. The phenotype resembles pseudoneonatal adrenoleukodystrophy with neurological deterioration and white matter abnormalities.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 0.462 OMIM phenotypes
Clinical SummaryACOX1
🧬
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.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.062
Z-score 3.97
OE 0.26 (0.160.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.98Z-score
OE missense 0.71 (0.640.79)
258 obs / 364.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.160.46)
00.351.4
Missense OE0.71 (0.640.79)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 9 / 34.0Missense obs/exp: 258 / 364.5Syn Z: 0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveACOX1-related adrenoleukodystrophy pseudoneonatalLOFAR

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

DN
0.7327th %ile
GOF
0.71top 25%
LOF
0.2189th %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.

Literature Evidence

GOFHowever, treatment of flies and primary Schwann cells with an antioxidant suppressed the p.N237S-induced neurodegeneration. In summary, both loss and gain of ACOX1 lead to glial and neuronal loss, but different mechanisms are at play and require different treatments.PMID:32169171

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →