PEX5 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PEX5 Gene - Peroxisome Biogenesis Factor 5</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PEX5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Peroxisome Biogenesis Factor 5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>12p13.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5835</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000120799</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P50571</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>3,786 bp (mRNA)</td>
</tr>
<tr>
<td class="label">Phenotype</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Severe Developmental Delay</td>
<td>Profound intellectual disability</td>
</tr>
<tr>
<td class="label">Neuronal Migration Defects</td>
<td>Abnormal brain development</td>
</tr>
<tr>
<td class="label">Hepatic Dysfunction</td>
<td>Liver disease, cholestasis</td>
</tr>
<tr>
<td class="label">Retinal Degeneration</td>
<td>Vision impairment</td>
</tr>
<tr>
<td class="label">Hearing Loss</td>
<td>Sensorineural deafness</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">PPAR agonists</td>
<td>Enhance peroxisome proliferation</td>
</tr>
<tr>
<td class="label">Ant
...PEX5 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PEX5 Gene - Peroxisome Biogenesis Factor 5</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PEX5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Peroxisome Biogenesis Factor 5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>12p13.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5835</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000120799</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P50571</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>3,786 bp (mRNA)</td>
</tr>
<tr>
<td class="label">Phenotype</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Severe Developmental Delay</td>
<td>Profound intellectual disability</td>
</tr>
<tr>
<td class="label">Neuronal Migration Defects</td>
<td>Abnormal brain development</td>
</tr>
<tr>
<td class="label">Hepatic Dysfunction</td>
<td>Liver disease, cholestasis</td>
</tr>
<tr>
<td class="label">Retinal Degeneration</td>
<td>Vision impairment</td>
</tr>
<tr>
<td class="label">Hearing Loss</td>
<td>Sensorineural deafness</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">PPAR agonists</td>
<td>Enhance peroxisome proliferation</td>
</tr>
<tr>
<td class="label">Antioxidants</td>
<td>Reduce oxidative stress</td>
</tr>
<tr>
<td class="label">VLCFA-lowering drugs</td>
<td>Reduce toxic metabolites</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Overview
Pex5 Gene Peroxisome Biogenesis Factor 5 plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
The PEX5 gene encodes Peroxisome Biogenesis Factor 5, a critical protein for peroxisome function and cellular homeostasis. PEX5 serves as the primary receptor for peroxisomal matrix protein import, recognizing proteins containing the peroxisomal targeting signal 1 (PTS1) tripeptide sequence[@gould1989]. Peroxisomes are essential organelles involved in fatty acid oxidation, [reactive oxygen species](/entities/reactive-oxygen-species) metabolism, and phospholipid synthesis—all processes critical for neuronal health.
Protein Structure
Pex5p (Peroxin-5)
- Molecular Weight: ~131 kDa
- Subcellular Localization: Cytosol and peroxisomal membrane
- Domain Architecture:
- N-terminal Domain: Binding site for PEX7 ( PTS2 receptor)
- TPR Domain: Tetratricopeptide repeat domain for cargo recognition
- C-terminal PTS1 Binding Pocket: Recognizes the SKL motif
Normal Function
Peroxisomal Protein Import
PEX5 is essential for importing proteins into the peroxisome matrix[@apanasets2014]:
Cargo Recognition: PEX5 binds PTS1-containing proteins (SKL motif) in the cytosol
Membrane Docking: The PEX5-cargo complex docks at the peroxisomal membrane translocon
Cargo Translocation: Cargo proteins are translocated into the peroxisome matrix
PEX5 Recycling: ATP-dependent recycling of PEX5 back to the cytosol by PEX1-PEX6 AAA ATPasesPeroxisome Biogenesis
PEX5 is crucial for:
- Formation of new peroxisomes ( proliferation)
- Import of peroxisomal matrix enzymes
- Peroxisome inheritance during cell division
Role in Peroxisome Function
Peroxisomes are essential for:
- β-Oxidation of Very Long-Chain Fatty Acids (VLCFAs): PEX5-dependent import of acyl-CoA oxidases
- Plasmalogen Synthesis: Ether phospholipids critical for myelin
- Bile Acid Synthesis: Cholesterol derivative metabolism
- Catalase Import: Key enzyme for hydrogen peroxide detoxification
- Peroxiredoxins: Antioxidant proteins
- Urate Oxidase: Purine metabolism
Disease Associations
Zellweger Spectrum Disorders
PEX5 mutations cause Zellweger syndrome, a severe peroxisome biogenesis disorder[@steinberg2004]:
Peroxisome Biogenesis Disorders (PBD)
- Infantile Refsum Disease: Milder form with later onset
- Neonatal Adrenoleukodystrophy: Progressive cerebral demyelination
Role in Neurodegenerative Diseases
Alzheimer's Disease
Peroxisomal dysfunction contributes to AD pathogenesis[@van2013]:
- VLCFA Accumulation: Impaired β-oxidation leads to membrane alterations
- Amyloid Metabolism: Peroxisomes regulate [amyloid precursor protein](/entities/app-protein) processing
- Oxidative Stress: Catalase deficiency increases ROS damage
- Lipid Homeostasis: Altered plasmalogen levels affect neuronal membranes
Parkinson's Disease
PEX5 dysfunction affects PD through:
- Mitochondrial-Peroxisomal Crosstalk: Both organelles communicate in quality control
- Pex5 in Dopaminergic [Neurons](/entities/neurons): High vulnerability to peroxisomal defects
- [Alpha-Synuclein](/proteins/alpha-synuclein) Clearance: Peroxisomes may participate in protein clearance
Amyotrophic Lateral Sclerosis (ALS)
- Peroxisomal Function: Impaired in ALS motor neurons
- VLCFA Metabolism: Abnormalities in motor neuron membranes
- Energy Metabolism: Peroxisomes support axonal energy demands
Huntington's Disease
- Peroxisome Numbers: Reduced in HD models
- Metabolic Dysfunction: Altered fatty acid metabolism
- Neuronal Vulnerability: Peroxisomal defects exacerbate degeneration
Therapeutic Implications
Gene Therapy
- AAV-PEX5: Viral vector delivery to restore peroxisomal function
- CRISPR-Cas9: Correct pathogenic PEX5 mutations
- mRNA Therapy: Deliver functional PEX5 mRNA
Pharmacological Approaches
Brain Expression
PEX5 is expressed throughout the brain:
- Cerebral [Cortex](/brain-regions/cortex): Pyramidal neurons, interneurons
- [Hippocampus](/brain-regions/hippocampus): CA neurons, dentate gyrus granule cells
- Cerebellum: Purkinje cells, granule cells
- Substantia Nigra: Dopaminergic neurons
- [Astrocytes](/entities/astrocytes) and Oligodendrocytes: Glial peroxisomes
Key Publications
[Dodt G, et al. The PTS1 receptor, PEX5, is a cycling cytosolic protein. J Cell Biol. 1995;131(5):1143-1156](https://doi.org/10.1083/jcb.131.5.1143)
[Francisco T, et al. Peroxisome biogenesis: The peroxisomal importomer. Cell Mol Life Sci. 2017;74(9):1567-1582](https://doi.org/10.1007/s00018-016-2442-4)
[Steinberg S, et al. Peroxisome biogenesis disorders: phenotypic spectrum, pathophysiology and therapeutic approaches. Orphanet J Rare Dis. 2015;10:7](https://doi.org/10.1186/s13023-015-0238-5)
[Waterham HR, Ebberink MS. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim Biophys Acta. 2012;1822(9):1430-1441](https://doi.org/10.1016/j.bbadis.2012.04.006)Pathway & Interaction Diagram
Interactive diagram showing PEX5's key relationships in the SciDEX knowledge graph (5 connections shown).
Mermaid diagram (expand to render)
See Also
- [PEX6 Protein](/proteins/pex6-protein)
- [PEX1 Gene](/genes/pex1)
- [Peroxisome](/mechanisms/peroxisome-biogenesis)
- [Zellweger Syndrome](/diseases/zellweger-syndrome)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Genes Index](/genes)
Overview
Pex5 Gene Peroxisome Biogenesis Factor 5 plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Pex5 Gene Peroxisome Biogenesis Factor 5 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
References
[Gould SG, et al., Identification of the peroxisomal targeting signal of firefly luciferase. Science. 1989;244(4907):986-990 (1989)](https://doi.org/10.1126/science.2499065)
[Apanasets O, et al., PEX5, the shuttling import receptor for peroxisomal matrix proteins, is a major cycling cytosolic protein. Biochim Biophys Acta. 2014;1843(12):2736-2746 (2014)](https://doi.org/10.1016/j.bbamcr.2014.08.008)
[Steinberg SJ, et al., Peroxisome biogenesis disorders: clinical, biochemical, and molecular studies. J Child Neurol. 2004;19(9):658-669 (2004)](https://doi.org/10.1177/08830738040190090201)
[Unknown, Van Veldhoven PP, Baes M. Peroxisome deficiency and disorders of peroxisome biogenesis. Biochim Biophys Acta. 2013;1832(1):1-13 (2013)](https://doi.org/10.1016/j.bbadis.2012.09.015)Pathway Diagram
The following diagram shows the key molecular relationships involving PEX5 Gene - Peroxisome Biogenesis Factor 5 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)