PEX10

Chr 1AR

peroxisomal biogenesis factor 10

NCBI Gene: 5192ENSG00000157911UniProt: O60683

E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (PubMed:24662292). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX10 also regulates PEX5 recycling by acting as a E3 ubiquitin-protein ligase (PubMed:24662292). When PEX5 recycling is compromised, PEX10 catalyzes polyubiquitination of PEX5 during its passage through the retrotranslocation channel, leading to its degradation (By similarity)

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 6A (Zellweger)MIM #614870
AR
Peroxisome biogenesis disorder 6BMIM #614871
AR
600
ClinVar variants
112
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PEX10
🧬
Gene-Disease Validity (ClinGen)
peroxisome biogenesis disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 Pathogenic / Likely Pathogenic· 198 VUS of 600 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.001
Z-score 1.99
OE 0.48 (0.28–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.29Z-score
OE missense 1.06 (0.95–1.18)
229 obs / 216.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.48 (0.28–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.95–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 8 / 16.8Missense obs/exp: 229 / 216.8Syn Z: 0.01

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic42
VUS198
Likely Benign278
Benign9
Conflicting3
70
Pathogenic
42
Likely Pathogenic
198
VUS
278
Likely Benign
9
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
4
39
0
70
Likely Pathogenic
32
1
9
0
42
VUS
1
179
17
1
198
Likely Benign
1
0
98
179
278
Benign
0
0
9
0
9
Conflicting
—3
Total61184172180600

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PEX10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PEX10-related peroxisome biogenesis disorder 6B

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

PEX10-related peroxisome biogenesis disorder 6A (Zellweger)

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Peroxisome biogenesis disorder 6A (Zellweger)

MIM #614870

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 6B

MIM #614871

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PEX10
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High rate of hypomorphic variants as the cause of inherited ataxia and related diseases: study of a cohort of 366 families.
Benkirane M et al.·Genet Med
2021Cohort
Ataxia with novel compound heterozygous PEX10 mutations and a literature review of PEX10-related peroxisome biogenesis disorders.
Zhang C et al.·Clin Neurol Neurosurg
2019Review
Mutations in PEX10 are a cause of autosomal recessive ataxia.
Régal L et al.·Ann Neurol
2010Review
Rare Variants Cause Charcot-Marie-Tooth Disease in Malian Families.
Yalcouyé A et al.·Brain Behav
2025
Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders.
Warren DS et al.·Am J Hum Genet
1998
Ataxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype.
Yamashita T et al.·J Neurol Sci
2017
Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.
Suzuki Y et al.·J Inherit Metab Dis
2001Review
Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: slowly progressive recessive ataxia.
Renaud M et al.·J Neurol
2016
Phenotype-genotype relationships in PEX10-deficient peroxisome biogenesis disorder patients.
Warren DS et al.·Hum Mutat
2000Cohort
Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.
Krause C et al.·Hum Mutat
2006Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools