PEX5

Chr 12AR

peroxisomal biogenesis factor 5

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.593 OMIM phenotypes
Clinical SummaryPEX5
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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.
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ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 78 VUS of 500 total submissions
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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

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.51
OE 0.38 (0.250.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.68Z-score
OE missense 0.90 (0.820.99)
325 obs / 361.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.250.59)
00.351.4
Missense OE0.90 (0.820.99)
00.61.4
Synonymous OE1.03
01.21.6
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

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

DN
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

500 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic18
VUS78
Likely Benign350
Benign7
Conflicting1
31
Pathogenic
18
Likely Pathogenic
78
VUS
350
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
1
8
0
31
Likely Pathogenic
15
2
1
0
18
VUS
4
68
3
3
78
Likely Benign
2
3
180
165
350
Benign
1
0
5
1
7
Conflicting
1
Total4474197169485

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →