PEX3

Chr 6AR

peroxisomal biogenesis factor 3

NCBI Gene: 8504ENSG00000034693UniProt: P56589

Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes

Primary Disease Associations & Inheritance

?Peroxisome biogenesis disorder 10BMIM #617370
AR
Peroxisome biogenesis disorder 10A (Zellweger)MIM #614882
AR
448
ClinVar variants
50
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— PEX3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 181 VUS of 448 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.016
Z-score 3.26
OE 0.31 (0.18–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.19Z-score
OE missense 0.76 (0.66–0.87)
145 obs / 191.1 exp
Tolerant

Mild missense constraint

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.0.31 (0.18–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.66–0.87)
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.0.89
0≤1.21.6
LoF obs/exp: 8 / 25.9Missense obs/exp: 145 / 191.1Syn Z: 0.70

ClinVar Variant Classifications

448 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic16
VUS181
Likely Benign169
Benign30
Conflicting14
34
Pathogenic
16
Likely Pathogenic
181
VUS
169
Likely Benign
30
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
24
0
34
Likely Pathogenic
10
3
3
0
16
VUS
4
129
45
3
181
Likely Benign
0
2
94
73
169
Benign
0
0
28
2
30
Conflicting
—14
Total2413419478444

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

View in ClinVar →

Protein Context — Lollipop Plot

PEX3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PEX3-related peroxisome biogenesis disorder 10B

strong
ARUndeterminedUncertain
Eye
G2P ↗

PEX3-related peroxisome biogenesis disorder

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Peroxisome biogenesis disorder 10B

MIM #617370

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 10A (Zellweger)

MIM #614882

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.
Suzuki Y et al.·J Inherit Metab Dis
2001Review
COVID-19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain.
Roczkowsky A et al.·Ann Neurol
2023
Hypomyelinating leukodystrophies in adults: Clinical and genetic features.
Di Bella D et al.·Eur J Neurol
2021
Peroxisomes protect lymphoma cells from HDAC inhibitor-mediated apoptosis.
Dahabieh MS et al.·Cell Death Differ
2017
Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene.
Matsui S et al.·Brain Dev
2013Case report
Genetic and Lifestyle-Related Factors Influencing Serum Hyper-Propionylcarnitine Concentrations and Their Association with Metabolic Syndrome and Cardiovascular Disease Risk.
Lee YH et al.·Int J Mol Sci
2023
Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder.
Bjørgo K et al.·Mol Genet Metab
2017Case report
Autophagy-mediated regulation patterns contribute to the alterations of the immune microenvironment in periodontitis.
Zhang X et al.·Aging (Albany NY)
2020
Zellweger syndrome with unusual findings: non-immune hydrops fetalis, dermal erythropoiesis and hypoplastic toe nails.
Dursun A et al.·J Inherit Metab Dis
2009Review
PEX3 is the causal gene responsible for peroxisome membrane assembly-defective Zellweger syndrome of complementation group G.
Ghaedi K et al.·Am J Hum Genet
2000
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools