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…

LOFmechanismARLOEUF 0.372 OMIM phenotypes

Clinical Summary— PEX26

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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)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

68 unique Pathogenic / Likely Pathogenic· 262 VUS of 618 total submissions

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GeneReview available — PEX26

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.37LOEUF

pLI 0.932

Z-score 3.08

OE 0.08 (0.03–0.37)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.37Z-score

OE missense 1.08 (0.96–1.22)

178 obs / 164.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.37)

0≤0.351.4

Missense OE?1.08 (0.96–1.22)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 1 / 13.0Missense obs/exp: 178 / 164.7Syn Z: -0.03

ClinVar Variant Classifications

618 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic33

VUS262

Likely Benign210

Benign36

Conflicting37

Pathogenic

Likely Pathogenic

262

VUS

210

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	31	2	2	0	35
Likely Pathogenic	23	8	2	0	33
VUS	2	188	71	1	262
Likely Benign	0	1	73	136	210
Benign	0	0	36	0	36
Conflicting	—				37
Total	56	199	184	137	613

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

View in ClinVar →

68 pathogenic / likely-pathogenic (of 80) ClinVar copy-number / structural variants overlap PEX26 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →