PEX5

Chr 12AR

peroxisomal biogenesis factor 5

Also known as: PBD2A, PBD2B, PTS1-BP, PTS1R, PXR1, RCDP5

NCBI Gene: 5830ENSG00000139197UniProt: P50542

The product of this gene binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause of neonatal adrenoleukodystrophy (NALD), a cause of Zellweger syndrome (ZWS) as well as may be a cause of infantile Refsum disease (IRD). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 2A (Zellweger)MIM #214110
AR
Peroxisome biogenesis disorder 2BMIM #202370
AR
Rhizomelic chondrodysplasia punctata, type 5MIM #616716
AR
185
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PEX5
🧬
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
27 Pathogenic / Likely Pathogenic· 31 VUS of 185 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.
0.59LOEUF
pLI 0.000
Z-score 3.51
OE 0.38 (0.25–0.59)
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.
0.68Z-score
OE missense 0.90 (0.82–0.99)
325 obs / 361.5 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.0.38 (0.25–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.99)
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.1.03
0≤1.21.6
LoF obs/exp: 14 / 37.1Missense obs/exp: 325 / 361.5Syn Z: -0.28

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic13
VUS31
Likely Benign124
Benign3
14
Pathogenic
13
Likely Pathogenic
31
VUS
124
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
10
0
14
Likely Pathogenic
7
2
4
0
13
VUS
2
26
2
1
31
Likely Benign
1
2
65
56
124
Benign
1
0
2
0
3
Total14318357185

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

View in ClinVar →

Protein Context — Lollipop Plot

PEX5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PEX5-related Zellweger syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

PEX5-related peroxisome biogenesis disorder 2B

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 2A (Zellweger)

MIM #214110

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 2B

MIM #202370

Molecular basis of disorder known

Autosomal recessive

Rhizomelic chondrodysplasia punctata, type 5

MIM #616716

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PEX5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
Loss of pex5 sensitizes zebrafish to fasting due to deregulated mitochondria, mTOR, and autophagy.
Bhandari S et al.·Cell Mol Life Sci
2023Functional
Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.
Suzuki Y et al.·J Inherit Metab Dis
2001Review
PEX14 condensates recruit receptor and cargo pairs for peroxisomal protein import.
Wu J et al.·Nat Struct Mol Biol
2025
Small molecule mediated inhibition of protein cargo recognition by peroxisomal transport receptor PEX5 is toxic to Trypanosoma.
Napolitano V et al.·Sci Rep
2022
Identification of Leishmania donovani PEX5-PTS1 Interaction Inhibitors through Fluorescence Polarization-Based High-Throughput Screening.
Phan TN et al.·Molecules
2024
Peroxisome biogenesis and molecular defects in peroxisome assembly disorders.
Fujiki Y et al.·Cell Biochem Biophys
2000Review
Polymorphism in the Hsa-miR-4274 seed region influences the expression of PEX5 and enhances radiotherapy resistance in colorectal cancer.
Lu Q et al.·Front Med
2024
Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective cell lines.
Ebberink MS et al.·Hum Mutat
2009
Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata.
Fallatah W et al.·J Inherit Metab Dis
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PEX5 integrates the p38 MAPK signaling pathway and taurine metabolism to regulate senescence in lung fibroblasts.
Zheng L et al.·Exp Cell Res
2026
TRIM37-mediated stabilization of PEX5 via monoubiquitination attenuates oxidative stress and demyelination in multiple sclerosis insights from EAE and LPC-induced experimental models.
Jiang L et al.·PLoS One
2025🔓 Open AccessFunctional
Detection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.
Bernal-Bonilla IT et al.·Appl Clin Genet
2025🔓 Open Access
Quantum mechanics-driven structure-activity relationship study of PEX5-PEX14 protein-protein interaction inhibitors based on a dibenzo[b,e]azepin-6(6H)-one scaffold.
Nowacki M et al.·Eur J Med Chem
2025
PEX5 deficiency enhances radiosensitivity via MGST1-GSH detoxifying function and promotes ferroptosis in liver cancer.
Yuan Z et al.·Sci China Life Sci
2025
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