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PEX10
peroxisomal biogenesis factor 10
PEX10 is located on the short (p) arm of chromosome 1, at band 1p36.32. Arm ratio per GRCh38 - banding schematic.
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Overview
PEX10 is located on chromosome 1 and belongs to a family of genes known as peroxins, which orchestrate the biogenesis of peroxisomes. Peroxisomes are small, membrane-bound organelles present in nearly all cells, responsible for breaking down very long-chain fatty acids, synthesising plasmalogens (specialised lipids crucial for myelin), and neutralising reactive oxygen species. The PEX10 protein acts as part of the machinery that recognises and transports newly synthesised enzymes from the cytoplasm into the peroxisomal interior. When PEX10 function is lost or severely impaired, peroxisomes fail to mature properly, resulting in a toxic accumulation of metabolic substrates and deficiency of essential lipid products. These biochemical disturbances underpin the clinical features of Zellweger spectrum disorders and related conditions.
What the gene does
The PEX10 protein is embedded in the peroxisomal membrane, where it forms part of a multi-protein complex required for importing proteins into the peroxisome matrix. Peroxisomal enzymes are synthesised in the cytoplasm and must be actively transported across the peroxisomal membrane to reach their site of function. PEX10 works alongside other peroxins to recognise cargo proteins tagged with specific signal sequences, facilitating their translocation into the organelle. This import machinery is essential for populating peroxisomes with the enzymes necessary for beta-oxidation of very long-chain fatty acids, plasmalogen synthesis, and degradation of hydrogen peroxide. Without functional PEX10, the peroxisomal import system stalls, leading to empty or non-functional peroxisomes. Cells then cannot efficiently metabolise certain lipids or detoxify reactive oxygen species, resulting in widespread cellular damage particularly affecting the nervous system, liver, and kidneys.
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Chromosome location
PEX10 is located on the short arm of chromosome 1 at position 36.32 (1p36.32). This chromosomal region is gene-dense and contains multiple loci associated with developmental and metabolic disorders. The gene spans approximately 16 kilobases of genomic DNA and comprises 6 exons that are transcribed and spliced to produce the mature messenger RNA template for PEX10 protein synthesis.
Protein structure
The PEX10 protein is 326 amino acids in length and contains a RING-type zinc finger domain spanning amino acids 273 to 311. The RING domain is a conserved structural motif that coordinates zinc ions and is typically involved in protein-protein interactions and ubiquitin ligase activity. In PEX10, this RING-type domain is thought to contribute to the assembly and function of the peroxisomal import complex, possibly by facilitating interactions with other peroxins or by modulating the activity of cargo receptors. The protein also includes a transmembrane segment that anchors it within the peroxisomal membrane, positioning the functional domains to interact with cytoplasmic and membrane-associated components of the import machinery.
Key variants
Pathogenic variants in PEX10 are inherited in an autosomal recessive pattern, meaning that affected individuals carry two altered copies of the gene, one inherited from each parent. Disease-causing changes include missense variants that disrupt the RING domain or transmembrane region, as well as nonsense and frameshift variants that result in truncated, non-functional protein. The severity of clinical manifestations can vary depending on the nature of the variants and the residual function of the PEX10 protein, with complete loss of function typically associated with the most severe phenotypes.
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.346_363delinsTGGGCCCCTG | p.Glu116fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder |
c.363del | p.Asp122fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder, complementation group 7 |
c.3G>A | p.Met1Ile | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder, complementation group 7 |
c.3G>C | p.Met1Ile | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder |
c.746G>A | p.Trp249Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.794_807del | p.Arg265fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder, complementation group 7 |
c.814_815insG | p.Leu272fs | Pathogenic/Likely pathogenic | ★★☆☆ | PEX10-related disorder |
c.858_870del | p.Pro287fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder, complementation group 7 |
c.882G>A | p.Trp294Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.8del | p.Pro3fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder, complementation group 7 |
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
Biallelic pathogenic variants in PEX10 cause peroxisomal biogenesis disorders, a group of rare autosomal recessive conditions that form part of the Zellweger spectrum. The most severe presentation, Zellweger syndrome, is characterised by profound neurological impairment, distinctive facial features, liver disease, and skeletal abnormalities, with affected infants often surviving only months. Milder forms on the spectrum, such as neonatal adrenoleukodystrophy and infantile Refsum disease, present with variable combinations of developmental delay, hearing and vision loss, liver dysfunction, and progressive white matter disease. The range of clinical severity reflects the degree of residual PEX10 function and the extent of peroxisomal impairment.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PEX10 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
PEX10 is included on multiple NHS Genomic Medicine Service panels, reflecting its relevance to a range of clinical presentations. The gene appears on green-rated panels for peroxisomal disorders, likely inborn errors of metabolism, undiagnosed metabolic disorders, and inherited white matter disorders, among others. Green classification indicates strong evidence supporting the gene-disease association. PEX10 is also listed on panels for neonatal cholestasis, intellectual disability, foetal anomalies, and hereditary neuropathy, consistent with the multisystem nature of peroxisomal biogenesis defects. Testing PEX10 may be considered in the diagnostic workup for individuals with suggestive biochemical findings, unexplained neurological decline, or relevant family history.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is PEX10-related peroxisomal disorder inherited?
PEX10-related conditions follow an autosomal recessive inheritance pattern. An affected individual inherits one pathogenic variant from each parent, both of whom are typically unaffected carriers. Carrier parents have a 25% chance with each pregnancy of having an affected child.
What is carrier screening for PEX10?
Carrier screening identifies individuals who carry one pathogenic PEX10 variant. Carriers are generally healthy but may be at risk of having affected children if their reproductive partner is also a carrier. Screening can inform family planning decisions and enable access to genetic counselling.
Can PEX10 variants be detected before birth?
Yes, if both parents are known carriers of PEX10 variants, prenatal diagnostic testing or preimplantation genetic testing can determine whether a pregnancy is affected. These options are discussed with a genetics specialist as part of reproductive planning.