PEX5 Gene - Peroxisome Biogenesis Factor 5

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.

Gene Information

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 ATPases

Peroxisome Biogenesis

PEX5 is crucial for:

• Formation of new peroxisomes ( proliferation)
• Import of peroxisomal matrix enzymes
• Peroxisome inheritance during cell division

Role in Peroxisome Function

Lipid Metabolism

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

ROS 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).

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: