PEX3

Chr 6AR

peroxisomal biogenesis factor 3

Also known as: PBD10A, PBD10B, TRG18

NCBI Gene: 8504 ENSG00000034693 UniProt: P56589 OMIM: 603164

The protein assembles membrane vesicles during peroxisome biogenesis before matrix protein translocation occurs. Mutations cause peroxisome biogenesis disorders including Zellweger syndrome, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects where mutant proteins disrupt normal peroxisome assembly and function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The product of this gene is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. 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 Zellweger syndrome (ZWS). [provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.562 OMIM phenotypes

Clinical Summary— PEX3

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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)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

38 unique Pathogenic / Likely Pathogenic· 179 VUS of 433 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PEX3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.016

Z-score 3.26

OE 0.31 (0.18–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.19Z-score

OE missense 0.76 (0.66–0.87)

145 obs / 191.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.18–0.56)

0≤0.351.4

Missense OE?0.76 (0.66–0.87)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 8 / 25.9Missense obs/exp: 145 / 191.1Syn Z: 0.70

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPEX3-related peroxisome biogenesis disorder 10BOTHERAR

definitivePEX3-related peroxisome biogenesis disorderLOFAR

This gene — mechanism propensity

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

0.6939th %ile

GOF

0.6053th %ile

LOF

0.3066th %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

433 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic17

VUS179

Likely Benign168

Benign30

Conflicting14

Pathogenic

Likely Pathogenic

179

VUS

168

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	19	0	2	0	21
Likely Pathogenic	14	3	0	0	17
VUS	5	130	40	4	179
Likely Benign	0	1	94	73	168
Benign	0	0	28	2	30
Conflicting	—				14
Total	38	134	164	79	429

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap PEX3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →