PEX2

Chr 8AR

peroxisomal biogenesis factor 2

Also known as: PAF1, PBD5A, PBD5B, PMP3, PMP35, PXMP3, RNF72, ZWS3

NCBI Gene: 5828ENSG00000164751UniProt: P28328

This gene encodes an integral peroxisomal membrane protein required for peroxisome biogenesis. The protein is thought to be involved in peroxisomal matrix protein import. Mutations in this gene result in one form of Zellweger syndrome and infantile Refsum disease. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 5A (Zellweger)MIM #614866
AR
Peroxisome biogenesis disorder 5BMIM #614867
AR
560
ClinVar variants
118
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— PEX2
🧬
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
118 Pathogenic / Likely Pathogenic· 259 VUS of 560 total submissions
💊
Clinical Trials
3 active or recruiting trials — 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.
1.20LOEUF
pLI 0.000
Z-score 1.11
OE 0.64 (0.36–1.20)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.05Z-score
OE missense 0.99 (0.87–1.13)
152 obs / 153.6 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.0.64 (0.36–1.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.87–1.13)
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.0.85
0≤1.21.6
LoF obs/exp: 7 / 11.0Missense obs/exp: 152 / 153.6Syn Z: 0.92

ClinVar Variant Classifications

560 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic49
VUS259
Likely Benign145
Benign21
Conflicting17
69
Pathogenic
49
Likely Pathogenic
259
VUS
145
Likely Benign
21
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
1
48
0
69
Likely Pathogenic
33
2
14
0
49
VUS
2
191
62
4
259
Likely Benign
0
1
13
131
145
Benign
0
2
18
1
21
Conflicting
—17
Total55197155136560

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

View in ClinVar →

Protein Context — Lollipop Plot

PEX2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PEX2-related peroxisome biogenesis disorder 5A (Zellweger)

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

PEX2-related peroxisome biogenesis disorder 5B

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Peroxisome biogenesis disorder 5A (Zellweger)

MIM #614866

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 5B

MIM #614867

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PEX2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Distinguishing PEX2 and PEX16 gene variant severity for mild, severe and atypical peroxisome biogenesis disorders.
Gomez VA et al.·Dis Model Mech
2025
HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption.
Chen L et al.·Int Dent J
2025
Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.
Suzuki Y et al.·J Inherit Metab Dis
2001Review
Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70.
Gärtner J et al.·Eur J Cell Biol
1998
Novel Genetic Variants and Clinical Profiles in Peters Anomaly Spectrum Disorders.
Delas F et al.·Int J Mol Sci
2025Case report
8q21.11 microdeletion in two patients with syndromic peters anomaly.
Happ H et al.·Am J Med Genet A
2016Review
Identification of sex-specific biomarkers related to programmed cell death and analysis of immune cells in ankylosing spondylitis.
Dong T et al.·Sci Rep
2024
Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.
Krause C et al.·Hum Mutat
2006Cohort
Identification of Shared and Asian-Specific Loci for Systemic Lupus Erythematosus and Evidence for Roles of Type III Interferon Signaling and Lysosomal Function in the Disease: A Multi-Ancestral Genome-Wide Association Study.
Wang YF et al.·Arthritis Rheumatol
2022Meta-analysis
Peroxisome biogenesis and molecular defects in peroxisome assembly disorders.
Fujiki Y et al.·Cell Biochem Biophys
2000Review
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
Zellweger Spectrum Disorder

Longitudinal Prospective Natural History Study of Retinopathy in Zellweger Spectrum Disorder

RECRUITING
NCT06190626McGill University Health Centre/Research Institute of the McGill University Health CentreStarted 2023-12-18
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08
Peroxisome Biogenesis DisorderZellweger Spectrum DisorderRCDP - Rhizomelic Chondrodysplasia Punctata

Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

RECRUITING
NCT01668186McGill University Health Centre/Research Institute of the McGill University Health CentreStarted 2012-01

External Resources

Links to major genomics databases and tools