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ACOX1
acyl-CoA oxidase 1
The ACOX1 gene provides instructions for producing peroxisomal straight-chain acyl-CoA oxidase, an enzyme crucial for the initial breakdown of very long-chain fatty acids within cellular peroxisomes. ACOX1 encodes an enzyme vital for metabolic processes, specifically initiating the degradation of very long-chain fatty acids (VLCFAs) in peroxisomes.
ACOX1 is located on the long (q) arm of chromosome 17, at band 17q25.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The ACOX1 gene is responsible for generating peroxisomal straight-chain acyl-CoA oxidase, an enzyme that plays a critical role in cellular metabolism. This enzyme is primarily active within peroxisomes, which are small, sac-like organelles found in cells. Its main function is to begin the breakdown of certain fat molecules, specifically very long-chain fatty acids (VLCFAs).
What the gene does
The peroxisomal straight-chain acyl-CoA oxidase enzyme, encoded by the ACOX1 gene, is integral to the peroxisomal fatty acid beta-oxidation pathway. This pathway systematically shortens VLCFA molecules by removing two carbon atoms at a time. The ACOX1 enzyme catalyses the initial step of this process, converting VLCFAs into acetyl-CoA, which can then be transported out of the peroxisomes and reused by the cell for energy or other metabolic functions. This breakdown is essential for preventing the accumulation of these fatty acids, which can be harmful if not processed correctly.
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Chromosome location
The ACOX1 gene is situated on chromosome 17, specifically at position 17q25.1. This location refers to the long (q) arm of chromosome 17, within region 25, band 1.
Protein structure
The ACOX1 protein is composed of 660 amino acids. It contains a specific sequence known as the Microbody targeting signal, located at amino acids 658-660. This motif is crucial for directing the protein to its correct cellular location within the peroxisomes.
Key variants
Genetic variations within the ACOX1 gene can influence the function of the peroxisomal straight-chain acyl-CoA oxidase enzyme. Some variants may alter the enzyme's structure or reduce its activity, thereby affecting its ability to break down very long-chain fatty acids. Over 20 such genetic changes have been identified in individuals with specific metabolic disorders.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1276_1277del | p.Val426fs | Pathogenic | ★★☆☆ | Mitchell syndrome |
c.1312del | p.Ser438fs | Pathogenic/Likely pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.139del | p.Gln47fs | Pathogenic/Likely pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.1502dup | p.Asn501fs | Pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.1704_1707del | p.Ser568fs | Pathogenic/Likely pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.1717del | p.Asp573fs | Pathogenic/Likely pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.1789_1792del | p.Leu596_Thr597insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.250G>T | p.Glu84Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Mitchell syndrome |
c.260G>A | p.Trp87Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
c.280C>T | p.Arg94Ter | Pathogenic | ★★☆☆ | Acyl-CoA oxidase deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the ACOX1 gene are associated with peroxisomal acyl-CoA oxidase deficiency. This condition arises when the ACOX1 enzyme cannot efficiently break down very long-chain fatty acids, leading to their accumulation in the body. The precise mechanisms by which this accumulation causes the specific features of peroxisomal acyl-CoA oxidase deficiency are still being investigated.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic ACOX1 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The ACOX1 gene is recognised in the UK National Health Service (NHS) Genomic Medicine Service. It is listed on several green R-panels in NHS England's PanelApp, indicating strong evidence for its association with various conditions. These include panels for Dystonia, chorea or related movement disorder (childhood onset), Foetal anomalies, Hereditary neuropathy or pain disorder, Inherited white matter disorders, Intellectual disability, Likely inborn error of metabolism, Peroxisomal disorders, Undiagnosed metabolic disorders, and White matter disorders and cerebral calcification (childhood onset).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the ACOX1 gene?
The ACOX1 gene provides instructions for an enzyme called peroxisomal straight-chain acyl-CoA oxidase. This enzyme is essential for the first step in breaking down very long-chain fatty acids (VLCFAs) within cellular peroxisomes.
What happens if the ACOX1 gene is not working correctly?
If the ACOX1 gene is not working correctly, the enzyme it produces cannot efficiently break down very long-chain fatty acids. This can lead to the accumulation of these fatty acids in the body, a condition known as peroxisomal acyl-CoA oxidase deficiency.
How does ACOX1 relate to peroxisomes?
The ACOX1 gene encodes an enzyme that performs its function primarily within peroxisomes, which are organelles responsible for various metabolic processes, including the breakdown of fatty acids. The ACOX1 protein has a specific signal that directs it to these peroxisomes.
References
- El Hajj HI, Vluggens A, Andreoletti P. The inflammatory response in acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy). Endocrinology. 2012. PMID: 22508517
- Carrozzo R, Bellini C, Lucioli S. Peroxisomal acyl-CoA-oxidase deficiency: two new cases. American journal of medical genetics. Part A. 2008. PMID: 18536048
- Ferdinandusse S, Denis S, Hogenhout EM. Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency. Human mutation. 2007. PMID: 17458872
- Kurian MA, Ryan S, Besley GT. Straight-chain acyl-CoA oxidase deficiency presenting with dysmorphia, neurodevelopmental autistic-type regression and a selective pattern of leukodystrophy. Journal of inherited metabolic disease. 2004. PMID: 15065573
- Suzuki Y, Iai M, Kamei A. Peroxisomal acyl CoA oxidase deficiency. The Journal of pediatrics. 2002. PMID: 11815777
- Clayton PT. Clinical consequences of defects in peroxisomal beta-oxidation. Biochemical Society transactions. 2001. PMID: 11356171
- Su HM, Moser AB, Moser HW. Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesis. The Journal of biological chemistry. 2001. PMID: 11500517