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ACOX1
acyl-CoA oxidase 1
The ACOX1 gene encodes an enzyme essential for the breakdown of very long-chain fatty acids within peroxisomes, playing a vital role in cellular metabolism. The ACOX1 gene provides the blueprint for peroxisomal straight-chain acyl-CoA oxidase, an enzyme located 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, also known as acyl-CoA oxidase 1, is integral to the metabolic processes within human cells. It carries the instructions for producing peroxisomal straight-chain acyl-CoA oxidase, an enzyme primarily found in peroxisomes. These organelles are responsible for breaking down various substances, including certain types of fatty acids.
Pathogenic variants in the ACOX1 gene are associated with peroxisomal acyl-CoA oxidase deficiency, an inherited condition that affects the body's ability to process these fats.
What the gene does
The ACOX1 gene directs the synthesis of the peroxisomal straight-chain acyl-CoA oxidase enzyme, which is critical for the initial step of peroxisomal fatty acid beta-oxidation. This pathway is responsible for shortening very long-chain fatty acids (VLCFAs) by removing two carbon atoms at a time.
This process converts VLCFAs into acetyl-CoA, a molecule that can then be transported out of the peroxisomes. Once outside, acetyl-CoA can be utilised by the cell for various metabolic activities, including energy production. The efficient functioning of the ACOX1 enzyme is therefore fundamental for proper lipid metabolism and preventing the accumulation of potentially harmful VLCFAs.
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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 arm (q) of chromosome 17, within region 25, band 1. Humans typically have two copies of chromosome 17, inheriting one from each parent.
Protein structure
The ACOX1 gene encodes a protein composed of 660 amino acids. A key feature of this protein is its C-terminal Microbody targeting signal, located at amino acids 658-660. This specific motif directs the ACOX1 protein to its correct cellular location within the peroxisomes, where it carries out its enzymatic function.
Key variants
Variants in the ACOX1 gene can impact the structure and function of the peroxisomal straight-chain acyl-CoA oxidase enzyme. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions within the gene sequence. Such alterations may lead to a non-functional or less efficient enzyme, thereby disrupting its role in fatty acid metabolism.
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 | ★★☆☆ | Mitchell syndrome |
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
Pathogenic variants in the ACOX1 gene are linked to peroxisomal acyl-CoA oxidase deficiency. This condition arises when the enzyme produced by the ACOX1 gene cannot effectively break down very long-chain fatty acids (VLCFAs). Consequently, these fatty acids accumulate within the body, which is thought to lead to the specific health features observed in affected individuals.
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 within several UK NHS Genomic Medicine Service (GMS) pathways, indicating its clinical relevance for genetic testing in the UK. It is listed with a 'green' status on NHS England's PanelApp for various conditions, including 'Dystonia, chorea or related movement disorder, childhood onset' (R57), 'Early onset or syndromic epilepsy', 'Foetal anomalies' (R21), 'Hereditary neuropathy or pain disorder' (R78), 'Inherited white matter disorders', 'Intellectual disability', 'Likely inborn error of metabolism' (R98), '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 ACOX1 gene responsible for?
The ACOX1 gene provides instructions for making an enzyme called peroxisomal straight-chain acyl-CoA oxidase. This enzyme is crucial for the first step in breaking down very long-chain fatty acids (VLCFAs) within cellular compartments called peroxisomes.
What happens if the ACOX1 gene doesn't work correctly?
If the ACOX1 gene has pathogenic variants, the enzyme it produces may not function efficiently. This can lead to a condition called peroxisomal acyl-CoA oxidase deficiency, where very long-chain fatty acids accumulate in the body because they cannot be properly broken down.
How is peroxisomal acyl-CoA oxidase deficiency inherited?
Peroxisomal acyl-CoA oxidase deficiency is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the ACOX1 gene, one from each parent, to develop the condition. People with only one altered copy are typically carriers and do not show symptoms.
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