PEX10

Chr 1AR

peroxisomal biogenesis factor 10

Also known as: NALD, PBD6A, PBD6B, RNF69

NCBI Gene: 5192 ENSG00000157911 UniProt: O60683 OMIM: 602859

The protein imports peroxisomal matrix proteins and localizes to the peroxisomal membrane. Mutations cause peroxisome biogenesis disorders within the Zellweger spectrum, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.862 OMIM phenotypes

Clinical Summary— PEX10

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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

151 unique Pathogenic / Likely Pathogenic· 328 VUS of 874 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PEX10

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?

0.86LOEUF

pLI 0.001

Z-score 1.99

OE 0.48 (0.28–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.29Z-score

OE missense 1.06 (0.95–1.18)

229 obs / 216.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.48 (0.28–0.86)

0≤0.351.4

Missense OE?1.06 (0.95–1.18)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 8 / 16.8Missense obs/exp: 229 / 216.8Syn Z: 0.01

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePEX10-related peroxisome biogenesis disorder 6BLOFAR

definitivePEX10-related peroxisome biogenesis disorder 6A (Zellweger)LOFAR

This gene — mechanism propensity

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

0.6840th %ile

GOF

0.5759th %ile

LOF

0.3164th %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

874 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64

Likely Pathogenic87

VUS328

Likely Benign335

Benign22

Conflicting33

Pathogenic

Likely Pathogenic

328

VUS

335

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	48	7	9	0	64
Likely Pathogenic	81	6	0	0	87
VUS	3	271	48	6	328
Likely Benign	2	5	112	216	335
Benign	0	2	16	4	22
Conflicting	—				33
Total	134	291	185	226	869

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

View in ClinVar →

126 pathogenic / likely-pathogenic (of 145) ClinVar copy-number / structural variants overlap PEX10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →