PEX2

Chr 8AR

peroxisomal biogenesis factor 2

Also known as: PAF1, PBD5A, PBD5B, PMP3, PMP35, PXMP3, RNF72, ZWS3

NCBI Gene: 5828 ENSG00000164751 UniProt: P28328 OMIM: 170993

The protein is an integral peroxisomal membrane protein required for peroxisome biogenesis and peroxisomal matrix protein import. Mutations cause peroxisome biogenesis disorders including Zellweger syndrome and infantile Refsum disease through autosomal recessive inheritance. The pathogenic mechanism involves dominant-negative effects disrupting normal peroxisome function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes an integral peroxisomal membrane protein required for peroxisome biogenesis. The protein is thought to be involved in peroxisomal matrix protein import. Mutations in this gene result in one form of Zellweger syndrome and infantile Refsum disease. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.202 OMIM phenotypes

Clinical Summary— PEX2

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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

95 unique Pathogenic / Likely Pathogenic· 254 VUS of 538 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PEX2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 1.11

OE 0.64 (0.36–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.05Z-score

OE missense 0.99 (0.87–1.13)

152 obs / 153.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.36–1.20)

0≤0.351.4

Missense OE?0.99 (0.87–1.13)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 7 / 11.0Missense obs/exp: 152 / 153.6Syn Z: 0.92

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePEX2-related peroxisome biogenesis disorder 5A (Zellweger)LOFAR

definitivePEX2-related peroxisome biogenesis disorder 5BLOFAR

This gene — mechanism propensity

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

0.7130th %ile

GOF

0.4875th %ile

LOF

0.3259th %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

538 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic60

VUS254

Likely Benign145

Benign21

Conflicting17

Pathogenic

Likely Pathogenic

254

VUS

145

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	32	1	2	0	35
Likely Pathogenic	58	2	0	0	60
VUS	3	194	53	4	254
Likely Benign	0	1	13	131	145
Benign	0	2	18	1	21
Conflicting	—				17
Total	93	200	86	136	532

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap PEX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →