PEX1

Chr 7AR

peroxisomal biogenesis factor 1

Also known as: HMLR1, PBD1A, PBD1B, ZWS, ZWS1

NCBI Gene: 5189ENSG00000127980UniProt: O43933

This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

Heimler syndrome 1MIM #234580
AR
Peroxisome biogenesis disorder 1A (Zellweger)MIM #214100
AR
Peroxisome biogenesis disorder 1B (NALD/IRD)MIM #601539
AR
582
ClinVar variants
103
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— PEX1
🧬
Gene-Disease Validity (ClinGen)
peroxisome biogenesis disorder due to PEX1 defect · 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
103 Pathogenic / Likely Pathogenic· 176 VUS of 582 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.66LOEUF
pLI 0.000
Z-score 3.86
OE 0.50 (0.38–0.66)
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.
1.14Z-score
OE missense 0.88 (0.82–0.94)
582 obs / 664.4 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.0.50 (0.38–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.82–0.94)
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.0.92
0≤1.21.6
LoF obs/exp: 35 / 69.8Missense obs/exp: 582 / 664.4Syn Z: 0.96

ClinVar Variant Classifications

582 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic56
VUS176
Likely Benign265
Benign34
Conflicting4
47
Pathogenic
56
Likely Pathogenic
176
VUS
265
Likely Benign
34
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
0
19
0
47
Likely Pathogenic
41
5
10
0
56
VUS
1
154
12
9
176
Likely Benign
1
3
141
120
265
Benign
0
1
33
0
34
Conflicting
—4
Total71163215129582

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

View in ClinVar →

Protein Context — Lollipop Plot

PEX1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PEX1-related Heimler syndrome

strong
ARUndeterminedAbsent Gene Product
SkinEar
G2P ↗

PEX1-related peroxisome biogenesis disorder

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersEyeSkin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Heimler syndrome 1

MIM #234580

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 1A (Zellweger)

MIM #214100

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 1B (NALD/IRD)

MIM #601539

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PEX1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Heimler Syndrome.
Mechaussier S et al.·Adv Exp Med Biol
2020Review
Ophthalmic Manifestations of Heimler Syndrome in Two Siblings With PEX1 Variants.
Miranda V et al.·J Pediatr Ophthalmol Strabismus
2024Review
PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.
Crane DI et al.·Hum Mutat
2005Review
Neonatal Cholestasis: Exploring Genetic Causes and Clinical Outcomes.
Gürcan Kaya N et al.·J Paediatr Child Health
2025
Spatial characterization of RPE structure and lipids in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder.
Omri S et al.·J Lipid Res
2025Functional
Heimler Syndrome With Tooth Agenesis, Abnormal Enamel and Dentin Mineralization, Root Maldevelopment, and PEX1 Mutation.
Kantaputra PN et al.·Int Dent J
2025Case report
Characterization of two common 5' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients.
Thoms S et al.·BMC Med Genet
2011Cohort
Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels.
Walter C et al.·Am J Hum Genet
2001
A novel compound heterozygous PEX1 variant in Heimler syndrome.
Yu M et al.·Exp Eye Res
2023Case report
Novel PEX1 mutations in fibroblasts from children with Zellweger spectrum disorders exhibit temperature sensitive characteristics.
Liang JS et al.·Epilepsy Behav
2023
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
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08
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
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