PEX26

Chr 22AR

peroxisomal biogenesis factor 26

Also known as: PBD7A, PBD7B, PEX26M1T, Pex26pM1T

NCBI Gene: 55670 ENSG00000215193 UniProt: Q7Z412 OMIM: 608666

The protein anchors PEX1 and PEX6 to peroxisome membranes to form AAA ATPase complexes required for importing proteins into peroxisomes. Mutations cause autosomal recessive peroxisome biogenesis disorders including Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and classical rhizomelic chondrodysplasia punctata due to failure of peroxisomal protein import. Loss-of-function mutations disrupt peroxisome assembly and function by preventing proper formation of the protein import machinery.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to the peroxin-26 gene family. It is probably required for protein import into peroxisomes. It anchors PEX1 and PEX6 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. Defects in this gene are the cause of peroxisome biogenesis disorder complementation group 8 (PBD-CG8). PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 7A (Zellweger)MIM #614872

Peroxisome biogenesis disorder 7BMIM #614873

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · peroxisome biogenesis disorder · AR · ClinGen 2020

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)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — PEX26

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in PEX26?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

397 rare PASS variants

Rare truncating (LoF)

1 in 2,500

57 rare PASS variants

Rare synonymous (reference)

1 in 310

185 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEX26. 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 140	1 in 2,800
South Asian	~43k	1 in 88	1 in 3,000
Remaining (unassigned)	~30k	1 in 160	1 in 4,300
European (Finnish)	~27k	1 in 170	1 in 3,000
Admixed American	~22k	1 in 130	1 in 1,300
African / African American	~21k	1 in 76	≈ 1 in 4,400
East Asian	~20k	1 in 220	1 in 3,300
Ashkenazi Jewish	~13k	1 in 490	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 100	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓