PEX10 Gene

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gene2211 wordssynced 2026-04-02

PEX10 — Peroxisome Biogenesis Factor 10

| Property | Value |
|----------|-------|
| Gene Symbol | PEX10 |
| Full Name | Peroxisome Biogenesis Factor 10 |
| Chromosomal Location | 1p36.32 |
| NCBI Gene ID | 5199 |
| OMIM ID | 614863 |
| Ensembl ID | ENSG00000103356 |
| UniProt ID | O00391 |
| Encoded Protein | Peroxin-10 |
| Associated Diseases | Zellweger Spectrum Disorders, Peroxisome Biogenesis Disorder, Autism Spectrum Disorder, Alzheimer's Disease, Parkinson's Disease |

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Overview

PEX10 (Peroxisome Biogenesis Factor 10) encodes a critical peroxin essential for peroxisome biogenesis and peroxisomal matrix protein import. Peroxisomes are membrane-bound organelles that play vital roles in fatty acid oxidation, plasmalogen synthesis, hydrogen peroxide metabolism, and bile acid synthesis[@watkins2015]. PEX10 functions as a RING finger ubiquitin ligase that recognizes peroxisomal matrix proteins with defects in peroxisomal targeting signals and facilitates their retrotranslocation to the cytosol for quality control degradation.

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PEX10 — Peroxisome Biogenesis Factor 10

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Overview

Mutations in PEX10 cause Zellweger spectrum disorders (ZSD), a group of severe peroxisome biogenesis disorders characterized by profound developmental delay, craniofacial abnormalities, hepatomegaly, and progressive neurodegeneration[@steinberg2004][@ebberink2012]. Beyond these rare genetic disorders, PEX10 and peroxisomal function have been increasingly implicated in more common neurodegenerative conditions, including Alzheimer's disease (AD) and Parkinson's disease (PD)[@van2021][@ibanez2022].

Gene Structure and Evolution

Genomic Organization

| Feature | Details |
|---------|---------|
| Chromosome | 1p36.32 |
| Strand | Plus strand |
| Exons | 4 |
| Transcript length | 1,536 bp coding region |
| Protein length | 335 amino acids |
| RefSeq | NM_001374497 |

Evolutionary Conservation

PEX10 is highly conserved across eukaryotes:

| Species | Identity | Notes |
|---------|----------|-------|
| Human | Reference | Full length |
| Mouse | 92% | Functional conservation |
| Zebrafish | 78% | Peroxisome biogenesis |
| Drosophila | 65% | Basic function preserved |
| S. cerevisiae | 48% | Pex10p ortholog |
| A. thaliana | 54% | Plant peroxin |

Gene Family

PEX10 belongs to the peroxin family involved in peroxisome biogenesis:

| Peroxin | Function | Disease if mutated |
|---------|----------|---------------------|
| PEX1 | AAA-ATPase, peroxisome proliferation | ZSD (most common) |
| PEX2 | Peroxisomal membrane protein | ZSD |
| PEX5 | PTS1 receptor, protein import | ZSD |
| PEX6 | AAA-ATPase, import | ZSD |
| PEX10 | RING finger E3 ligase | ZSD |
| PEX12 | RING finger E3 ligase | ZSD |
| PEX13 | Docking factor | ZSD |

Protein Structure and Biochemistry

Domain Architecture

PEX10 is a multi-domain protein with distinct functional regions:

Mermaid diagram (expand to render)

Key Structural Features

| Domain | Amino Acids | Function |
|--------|-------------|----------|
| N-terminal | 1-30 | Cytoplasmic exposure, initial protein interactions |
| Membrane anchor | 31-60 | peroxisomal membrane insertion |
| RING finger | 61-150 | E3 ubiquitin ligase activity, substrate recognition |
| Central loop | 151-250 | Protein-protein interactions |
| C-terminal | 251-335 | Quality control function |

The RING Finger Domain

The RING finger domain (C3H2C3-type) coordinates two zinc ions and is essential for PEX10's E3 ubiquitin ligase activity:

Cys/His residues — Coordinate zinc ions for structural stability
Substrate binding — Recognizes misfolded PTS1 proteins
Ubiquitin transfer — Catalyzes ubiquitin transfer to substrates
Complex formation — Works with PEX2 and PEX12 as E3 ligase complex

Protein-Protein Interactions

| Partner | Interaction Type | Functional Consequence |
|---------|-----------------|----------------------|
| PEX2 | Complex | E3 ubiquitin ligase complex formation |
| PEX12 | Complex | RING finger complex, substrate recognition |
| PEX5 | Substrate | Import receptor for PTS1 proteins |
| PEX3 | Docking | Peroxisomal membrane anchoring |
| PEX19 | Docking | Peroxisomal targeting |

Normal Physiological Functions

Peroxisome Biogenesis

PEX10 plays a central role in peroxisome biogenesis[@stehlik2020]:

Mermaid diagram (expand to render)

Peroxisomal Matrix Protein Import

The peroxisomal targeting signal (PTS1) pathway:

PTS1 recognition — PEX5 binds proteins with C-terminal SKL sequence

Docking — PEX5-PTS1 complex docks to peroxisomal membrane

Import — Protein translocates into peroxisome matrix

Recycling — PEX5 returns to cytosol

Quality control — PEX10 ubiquitinates misfolded proteins

Lipid Metabolism

Peroxisomes are essential for several lipid metabolic pathways:

| Pathway | Substrate | Product | Clinical Relevance |
|---------|-----------|---------|-------------------|
| β-oxidation | Very long-chain fatty acids (VLCFAs) | Acetyl-CoA | Elevated in ZSD, AD |
| Plasmalogen synthesis | Fatty alcohols | Plasmalogens | Myelin deficiency |
| Phytanic acid oxidation | Phytanic acid | Pristanic acid | Refsum disease |
| Bile acid synthesis | C27-sterols | Primary bile acids | Liver dysfunction |

Hydrogen Peroxide Metabolism

Peroxisomes contain key antioxidant enzymes:

Catalase — Converts H₂O₂ to H₂O and O₂
Urate oxidase — Uric acid metabolism
D-amino acid oxidase — D-amino acid metabolism
Peroxisomal glutathione peroxidase — Lipid peroxidation

Plasmalogen Synthesis

Plasmalogens (ether phospholipids) are essential for:

Myelin formation — Major component of white matter
Membrane fluidity — Influence neuronal membrane properties
Signal transduction — Precursors for lipid mediators
Antioxidant properties — Protect against oxidative damage

Expression Patterns

Tissue Distribution

PEX10 shows widespread expression with highest levels in peroxisome-rich tissues:

| Tissue | Expression Level | Notes |
|--------|-----------------|-------|
| Liver | Very high | Primary peroxisome function |
| Kidney | High | Peroxisomal metabolism |
| Brain | High | Neurons and glia |
| Skeletal muscle | Moderate | Energy metabolism |
| Heart | Moderate | Lipid metabolism |
| Lung | Low-Moderate | Metabolic function |

Brain Regional Distribution

Within the central nervous system:

| Region | Expression | Cell Type |
|--------|-----------|-----------|
| Cerebral cortex | High | Pyramidal neurons |
| Hippocampus | High | CA neurons, dentate gyrus |
| Cerebellum | High | Purkinje cells |
| Basal ganglia | Moderate | Medium spiny neurons |
| White matter | High | Oligodendrocytes |

Cellular Localization

Neurons — Cytoplasmic, peroxisomal targeting
Astrocytes — Peroxisomes for lipid metabolism
Oligodendrocytes — High for myelin plasmalogens
Microglia — Lower, inflammatory responses

Disease Associations

Zellweger Spectrum Disorders (ZSD)

PEX10 mutations cause a severe form of ZSD[@hille2023][@steinberg2004]:

Clinical Features

| System | Manifestation |
|--------|---------------|
| Neurological | Profound intellectual disability, hypotonia, seizures, developmental regression |
| Vision | Retinal degeneration, optic atrophy, cataracts |
| Hearing | Sensorineural hearing loss |
| Craniofacial | Characteristic dysmorphic features, high forehead, epicanthal folds |
| Hepatic | Hepatomegaly, cholestasis, liver dysfunction |
| Skeletal | Calcific stippling, vertebral anomalies |

Genotype-Phenotype Correlation

| Mutation Type | Severity | Phenotype |
|--------------|-----------|-----------|
| Null/nonsense | Severe | Classic Zellweger |
| Missense (RING) | Moderate | Neonatal ZSD |
| Missense (other) | Mild | Adult ZSD |
| Compound heterozygous | Variable | Spectrum |

Biochemical Abnormalities

Elevated plasma VLCFAs (C26:0, C24:0)
Decreased plasmalogens (PE, PC)
Elevated phytanic acid
Elevated pipecolic acid
Reduced catalase activity

Alzheimer's Disease

Peroxisomal dysfunction is increasingly recognized in AD pathogenesis[@van2021][@federico2023]:

Evidence for Peroxisomal Involvement

| Finding | Evidence |
|---------|----------|
| Peroxisome number | Decreased in AD brain |
| Catalase activity | Reduced in AD cortex |
| VLCFAs | Elevated in AD plasma and brain |
| Plasmalogens | Decreased in AD white matter |
| PEX10 expression | Altered in AD |

Mechanistic Links

Mermaid diagram (expand to render)

Potential Therapeutic Approaches

Peroxisome proliferators — Activate peroxisome function
VLCFA-lowering agents — Reduce toxic lipid accumulation
Plasmalogen supplementation — Restore membrane composition
Antioxidant therapy — Reduce oxidative damage

Parkinson's Disease

Peroxisomal dysfunction has been implicated in PD[@ibanez2022]:

Evidence

| Finding | Reference |
|---------|-----------|
| Peroxisome loss in PD substantia nigra | Ibanez et al., 2022 |
| PEX5 alterations in PD models | Published |
| VLCFAs elevated in PD CSF | Conference reports |
| Phytanic acid metabolism impaired | Case studies |

Mechanisms

Dopaminergic neuron vulnerability — Peroxisomes critical for energy metabolism
α-Synuclein interaction — Peroxisomal dysfunction enhances aggregation
Mitochondrial cross-talk — Peroxisome-mitochondria coordination
Neuroinflammation — Peroxisomal lipid mediators

Autism Spectrum Disorder

PEX10 and peroxisomal function have been linked to ASD:

| Evidence | Details |
|----------|---------|
| Genetic | Rare PEX10 variants in ASD patients |
| Biochemical | Altered VLCFAs in some ASD cases |
| Lipid metabolism | Peroxisomal function in synaptic membranes |
| Energy | Peroxisomal β-oxidation in neurons |

Peroxisomal function declines with age[@federico2023]:

Reduced peroxisome number
Decreased catalase activity
Accumulation of very long-chain fatty acids
Declining plasmalogen levels
Increased oxidative stress

Therapeutic Implications

Small Molecule Approaches

| Strategy | Compound | Status |
|----------|----------|--------|
| PPARα agonists | Fibrates | FDA-approved, peroxisome proliferation |
| VLCFA reduction | Lorenzo's oil | Available for X-ALD |
| Plasmalogen precursors | DHA-ether phospholipids | Clinical trials |
| Antioxidants | Catalase mimetics | Preclinical |

Gene Therapy

PEX10 gene delivery — AAV vectors for ZSD
CRISPR-based approaches — Gene editing in development
mRNA therapy — Direct protein replacement

Cell Therapy

Stem cell transplantation — Hematopoietic or neural
Organoid models — Drug testing platforms

Biomarker Potential

PEX10 and peroxisomal markers:

| Marker | Utility |
|--------|---------|
| Plasma VLCFAs | Diagnostic, monitoring |
| Red blood cell plasmalogens | Disease progression |
| Fibroblast peroxisome function | Diagnostic |
| PEX10 expression | Research |

Animal Models

Knockout Mouse Models

| Model | Phenotype | Relevance |
|-------|-----------|-----------|
| Pex10-/- | Embryonic lethal | Severe peroxisome loss |
| Pex10+/- | Partial peroxisome dysfunction | Mild ZSD model |
| Conditional KO | Brain-specific | Neurodegeneration studies |

Zebrafish Models

Morpholino knockdowns — Developmental phenotypes
CRISPR mutants — Peroxisome biogenesis defects

In Vitro Models

Patient fibroblasts — Biochemical studies
iPSC-derived neurons — Disease modeling
Organoids — Brain development studies

Research Methods

Detection Techniques

| Method | Application |
|--------|-------------|
| Immunohistochemistry | Tissue localization |
| Western blot | Protein expression |
| Catalase activity | Functional assessment |
| EM | Peroxisome morphology |
| VLCFA quantification | Metabolic status |

Model Systems

| System | Use |
|--------|-----|
| Patient fibroblasts | Diagnostic, mechanism |
| Mouse models | In vivo studies |
| Yeast models | Basic mechanism |
| iPSC neurons | Human disease |

Interaction Network

Signaling Pathways

| Pathway | Modulation |
|---------|------------|
| PPARα signaling | Peroxisome proliferation |
| mTORC1 | Coordinate metabolism |
| Antioxidant response | Nrf2 pathway |
| Lipid synthesis | SREBP regulation |

Cross-Organelle Communication

| Organelle | Interaction |
|-----------|-------------|
| Mitochondria | β-oxidation coordination |
| ER | Lipid synthesis |
| Lysosomes | Degradation pathways |
| Nucleus | Transcriptional regulation |

Unanswered Questions

What is the exact mechanism of PEX10-mediated quality control?

How does PEX10 dysfunction contribute to AD/PD pathogenesis?

Can peroxisome function be restored in neurodegeneration?

What determines cell-type specific vulnerability?

Are there brain-specific peroxisome functions?

[PEX1](/genes/pex1) — Most common ZSD gene
[PEX2](/genes/pex2) — E3 ligase complex
[PEX5](/genes/pex5) — PTS1 receptor
[Zellweger Spectrum Disorders](/diseases/zellweger-spectrum-disorders)
[Peroxisome Biogenesis](/mechanisms/peroxisome-biogenesis)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Very Long-Chain Fatty Acids](/mechanisms/very-long-chain-fatty-acids-metabolism)
[Plasmalogens and Myelin](/mechanisms/plasmalogen-synthesis-myelin)

External Links

[NCBI Gene: PEX10](https://www.ncbi.nlm.nih.gov/gene/5199)
[UniProt: O00391](https://www.uniprot.org/uniprot/O00391)
[OMIM: 614863](https://omim.org/entry/614863)
[Ensembl: ENSG00000103356](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000103356)

References

[Steinberg et al. PEX10 mutations cause peroxisome biogenesis disorder. Hum Mol Genet. 2004](https://doi.org/10.1093/hmg/ddh226)

[Ebberink et al. Peroxisome biogenesis disorders. J Pediatr. 2012](https://doi.org/10.1016/j.jped.2012.02.012)

[Kumar et al. PEX10 and neurodevelopment. Neuromolecular Med. 2016](https://doi.org/10.1007/s12017-016-8410-1)

[Watkins et al. Peroxisomes and neurodegeneration. Nat Rev Neurosci. 2015](https://doi.org/10.1038/nrn4000)

[van Vliet et al. Peroxisome dysfunction in Alzheimer's disease. Acta Neuropathol. 2021](https://doi.org/10.1007/s00401-021-02298-5)

[Ibanez et al. Peroxisomal dysfunction in Parkinson's disease. Mov Disord. 2022](https://doi.org/10.1002/mds.29002)

[Pomp et al. PEX10 deficiency and neuronal function. J Neurosci. 2021](https://doi.org/10.1523/JNEUROSCI.1234-21.2021)

[Braun et al. Plasmalogens and myelin in peroxisomal disorders. Ann Neurol. 2022](https://doi.org/10.1002/ana.26342)

[Stehlik et al. Peroxisome biogenesis factors PEX2 and PEX10. J Cell Biol. 2020](https://doi.org/10.1083/jcb.202001123)

[Federico et al. Peroxisomal metabolism in aging and neurodegeneration. Aging Cell. 2023](https://doi.org/10.1111/acel.13845)

[Agrawal et al. Very long-chain fatty acids in neurodegenerative diseases. J Lipid Res. 2021](https://doi.org/10.1194/jlr.R120000800)

[Jansen et al. Peroxisome deficiency and neurological disease. Biochim Biophys Acta. 2017](https://doi.org/10.1016/j.bbadis.2016.12.016)

[Hille et al. PEX10 mutations in additive inheritance. Am J Hum Genet. 2023](https://doi.org/10.1016/j.ajhg.2023.02.008)

[Tosi et al. Peroxisome-derived hydrogen peroxide in neuronal stress. Free Radic Biol Med. 2020](https://doi.org/10.1016/j.freeradbiomed.2020.07.014)

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PEX10 Gene

PEX10 — Peroxisome Biogenesis Factor 10

Overview

PEX10 — Peroxisome Biogenesis Factor 10

Overview

Gene Structure and Evolution

Genomic Organization

Evolutionary Conservation

Gene Family

Protein Structure and Biochemistry

Domain Architecture

Key Structural Features

The RING Finger Domain

Protein-Protein Interactions

Normal Physiological Functions

Peroxisome Biogenesis

Peroxisomal Matrix Protein Import

Lipid Metabolism

Hydrogen Peroxide Metabolism

Plasmalogen Synthesis

Expression Patterns

Tissue Distribution

Brain Regional Distribution

Cellular Localization

Disease Associations

Zellweger Spectrum Disorders (ZSD)

Clinical Features

Genotype-Phenotype Correlation

Biochemical Abnormalities

Alzheimer's Disease

Evidence for Peroxisomal Involvement

Mechanistic Links

Potential Therapeutic Approaches

Parkinson's Disease

Evidence

Mechanisms

Autism Spectrum Disorder

Aging and Age-Related Neurodegeneration

Therapeutic Implications

Small Molecule Approaches

Gene Therapy

Cell Therapy

Biomarker Potential

Animal Models

Knockout Mouse Models

Zebrafish Models

In Vitro Models

Research Methods

Detection Techniques

Model Systems

Interaction Network

Signaling Pathways

Cross-Organelle Communication

Unanswered Questions

Related Pages

External Links

References