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…

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 6A (Zellweger)MIM #614870

Peroxisome biogenesis disorder 6BMIM #614871

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · peroxisome biogenesis disorder · AR · ClinGen 2019

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in PEX10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

542 rare PASS variants

Rare truncating (LoF)

1 in 1,200

99 rare PASS variants

Rare synonymous (reference)

1 in 110

224 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEX10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 99	1 in 1,100
South Asian	~43k	1 in 66	1 in 1,500
Remaining (unassigned)	~30k	1 in 73	1 in 2,200
European (Finnish)	~27k	1 in 190	1 in 4,200
Admixed American	~22k	1 in 67	1 in 610
African / African American	~21k	1 in 79	1 in 2,800
East Asian	~20k	1 in 80	1 in 820
Ashkenazi Jewish	~13k	1 in 450	1 in 1,300
Middle Eastern	~2,884	1 in 68	1 in 340

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓