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PEX13
peroxisomal biogenesis factor 13
PEX13 is located on the short (p) arm of chromosome 2, at band 2p15. Arm ratio per GRCh38 - banding schematic.
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Overview
PEX13 (peroxisomal biogenesis factor 13) is located on chromosome 2 at position 2p15 and encodes a 403-amino-acid protein that plays an essential role in peroxisome function. Peroxisomes are small cellular compartments responsible for breaking down fatty acids, synthesising plasmalogens (lipids critical for myelin formation), and detoxifying reactive oxygen species. The PEX13 protein serves as a receptor on the peroxisomal membrane, enabling the import of enzymes required for these metabolic processes. When PEX13 function is lost, peroxisomes cannot assemble properly, resulting in a spectrum of severe metabolic disorders that typically present in infancy or early childhood with neurological deterioration, liver disease, and developmental impairment.
What the gene does
The PEX13 protein functions as an integral membrane receptor embedded in the peroxisomal membrane, where it recognises and binds cargo proteins destined for import into the peroxisome interior. It works in conjunction with other peroxins (peroxisome assembly proteins) to facilitate the translocation of enzymes across the membrane. The protein interacts directly with PEX14 and PEX5, forming a docking complex that captures peroxisomal matrix proteins carrying specific targeting signals. This import machinery is essential for populating peroxisomes with the enzymes necessary for very-long-chain fatty acid oxidation, bile acid synthesis, and plasmalogen production. Without functional PEX13, peroxisomes remain empty or fail to form altogether, leading to the accumulation of toxic metabolites in tissues and disruption of lipid metabolism throughout the body.
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Chromosome location
PEX13 is located on the short arm of chromosome 2 at band 2p15. The gene spans genomic DNA on this chromosomal region and encodes a protein of 403 amino acids. Its position on chromosome 2 places it among other genes involved in metabolic and developmental processes, though PEX13 itself is specifically dedicated to peroxisomal biogenesis.
Protein structure
The PEX13 protein comprises several functionally distinct regions across its 403-amino-acid sequence. The N-terminal portion (amino acids 1-68) is disordered and likely provides structural flexibility. A targeting to peroxisomes region spans amino acids 145-233, directing the protein to the peroxisomal membrane. Within this region, amino acids 175-196 mediate interaction with PEX19, another peroxin involved in membrane protein insertion. The C-terminal portion contains an SH3 domain (amino acids 272-336), a protein-protein interaction module that binds PEX5 and PEX14, enabling formation of the import complex essential for cargo recognition and translocation.
Key variants
Pathogenic variants in PEX13 are inherited in an autosomal recessive pattern, meaning affected individuals carry alterations in both gene copies. These variants typically result in loss of protein function through mechanisms including premature termination, frameshift mutations, or missense changes that disrupt the SH3 domain or membrane-targeting regions. The variant spectrum includes both null alleles that abolish protein production and hypomorphic variants that retain partial function, with the latter sometimes associated with milder 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.367G>T | p.Glu123Ter | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 11A (Zellweger) |
c.391C>T | p.Gln131Ter | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder |
c.465T>G | p.Tyr155Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 11A (Zellweger) |
c.508C>T | p.Arg170Ter | Pathogenic/Likely pathogenic | ★★☆☆ | PEX13-related disorder |
c.573_582del | p.Arg193fs | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder |
c.676C>T | p.Arg226Ter | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 11A (Zellweger) |
c.107del | p.Gly36fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 11A (Zellweger) |
c.294T>G | p.Tyr98Ter | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 11A (Zellweger) |
c.296del | p.Gly99fs | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 4A (Zellweger) |
c.544_545insAAT | p.Phe182Ter | Pathogenic | ★☆☆☆ | Peroxisome biogenesis disorder 11A (Zellweger) |
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 PEX13 cause peroxisomal biogenesis disorders, a group of rare autosomal recessive conditions characterised by absent or dysfunctional peroxisomes. The clinical severity ranges from severe neonatal presentations with profound neurological impairment, liver failure, and characteristic facial features, to milder childhood-onset forms with intellectual disability, vision loss, and progressive neurological decline. Common features across the spectrum include elevated very-long-chain fatty acids in blood, reduced plasmalogen levels, and accumulation of metabolic intermediates that would normally be processed within peroxisomes.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PEX13 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
PEX13 appears on multiple NHS Genomic Medicine Service panels with green (high evidence) status, reflecting its established role in genetic diagnosis. It is included in panels for peroxisomal disorders, likely inborn errors of metabolism, undiagnosed metabolic disorders, inherited white matter disorders, intellectual disability, neonatal cholestasis, foetal anomalies, foetal hydrops, bilateral congenital or childhood onset cataracts, arthrogryposis, malformations of cortical development, adult onset leukodystrophy, and white matter disorders with cerebral calcification. This wide panel membership reflects the diverse clinical presentations of peroxisomal biogenesis disorders and ensures that PEX13 is analysed when patients present with compatible features through NHS diagnostic pathways.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the inheritance pattern for PEX13-related conditions?
Conditions associated with PEX13 variants are inherited in an autosomal recessive pattern. This means an individual must inherit a pathogenic variant from both parents to develop the condition. Carriers with one altered copy typically remain unaffected.
How common are PEX13 pathogenic variants?
PEX13-related peroxisomal biogenesis disorders are rare, with exact carrier frequencies varying by population. Collectively, peroxisomal disorders affect approximately 1 in 50,000 births, with PEX13 variants accounting for a subset of these cases.
Can PEX13 variants cause different severities of disease?
Yes, the clinical severity of PEX13-related conditions can vary depending on the specific variants inherited. Complete loss of protein function typically causes severe neonatal presentations, whilst variants retaining some residual activity may result in milder childhood-onset forms with longer survival.