PEX5

Chr 12AR

peroxisomal biogenesis factor 5

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

NCBI Gene: 5830 ENSG00000139197 UniProt: P50542 OMIM: 600414

The protein functions as a receptor that binds to C-terminal PTS1-type peroxisomal targeting signals and mediates the import of proteins into the peroxisome matrix. Autosomal recessive mutations cause peroxisome biogenesis disorders including Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and rhizomelic chondrodysplasia punctata type 5. These conditions result from defective peroxisomal protein import, leading to multiple defects in peroxisome function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.593 OMIM phenotypes

Clinical Summary— PEX5

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Gene-Disease Validity (ClinGen)

peroxisome biogenesis disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

77 unique Pathogenic / Likely Pathogenic· 424 VUS of 1095 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PEX5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.68Z-score

OE missense 0.90 (0.82–0.99)

325 obs / 361.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.25–0.59)

0≤0.351.4

Missense OE?0.90 (0.82–0.99)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 14 / 37.1Missense obs/exp: 325 / 361.5Syn Z: -0.28

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePEX5-related Zellweger syndromeLOFAR

definitivePEX5-related peroxisome biogenesis disorder 2BLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6261th %ile

GOF

0.6735th %ile

LOF

0.3163th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1095 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44

Likely Pathogenic33

VUS424

Likely Benign461

Benign64

Conflicting54

Pathogenic

Likely Pathogenic

424

VUS

461

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	42	1	1	0	44
Likely Pathogenic	29	4	0	0	33
VUS	8	343	64	9	424
Likely Benign	3	3	225	230	461
Benign	1	3	58	2	64
Conflicting	—				54
Total	83	354	348	241	1,080

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap PEX5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →