PEX26

peroxisomal biogenesis factor 26, the group of Peroxins

Basic information

Region (hg38): 22:18077923-18105396

Links

ENSG00000215193

∙ NCBI:55670 ∙ OMIM:608666 ∙ HGNC:22965 ∙ Uniprot:Q7Z412 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Zellweger spectrum disorders (Supportive), mode of inheritance: AR
peroxisome biogenesis disorder 7B (Definitive), mode of inheritance: AR
peroxisome biogenesis disorder 7A (Zellweger) (Strong), mode of inheritance: AR
peroxisome biogenesis disorder (Definitive), mode of inheritance: AR
peroxisome biogenesis disorder 7A (Zellweger) (Definitive), mode of inheritance: AR
peroxisome biogenesis disorder 7B (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peroxisome biogenesis disorder 7A; Peroxisome biogenesis disorder 7B; Adrenoleukodystrophy, neonatal; Refsum disease, infantile	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	12851857; 12717447; 15542397; 15858711; 19105186

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX26 gene.

Peroxisome_biogenesis_disorder_7A_(Zellweger) (451 variants)
Peroxisome_biogenesis_disorder_7B (435 variants)
not_provided (75 variants)
Inborn_genetic_diseases (45 variants)
PEX26-related_disorder (26 variants)
not_specified (18 variants)
Peroxisome_biogenesis_disorder (9 variants)
Retinal_dystrophy (2 variants)
Optic_atrophy (1 variants)
Peroxisome_biogenesis_disorder_1A_(Zellweger) (1 variants)
Heimler_syndrome_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX26 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001127649.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		2 clinvar	146 clinvar		149
missense	1 clinvar	10 clinvar	186 clinvar	10 clinvar	1 clinvar	208
nonsense	10 clinvar	4 clinvar				14
start loss	1	2				3
frameshift	19 clinvar	11 clinvar	1 clinvar			31
splice donor/acceptor (+/-2bp)	2 clinvar	6 clinvar				8
Total	34	33	189	156	1

Highest pathogenic variant AF is 0.0000867424

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX26	protein_coding	protein_coding	ENST00000329627	5	53217

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.932	0.0680	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.368	178	165	1.08	0.00000919	1913
Missense in Polyphen		51	60.562	0.84212		762
Synonymous	-0.0326	73	72.6	1.00	0.00000373	656
Loss of Function	3.08	1	13.0	0.0772	6.60e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000212
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000111	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000682	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Probably required for protein import into peroxisomes. Anchors PEX1 and PEX6 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. Involved in the import of catalase and proteins containing a PTS2 target sequence, but not in import of proteins with a PTS1 target sequence. {ECO:0000269|PubMed:12717447, ECO:0000269|PubMed:12851857}.;
Disease: DISEASE: Peroxisome biogenesis disorder 7A (PBD7A) [MIM:614872]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. {ECO:0000269|PubMed:12851857}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 7B (PBD7B) [MIM:614873]: A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. {ECO:0000269|PubMed:12717447, ECO:0000269|PubMed:12851857}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Peroxisome - Homo sapiens (human);Metabolism of proteins;Peroxisomal protein import (Consensus)

Intolerance Scores

loftool: 0.105
rvis_EVS: 1.13
rvis_percentile_EVS: 92.16

Haploinsufficiency Scores

pHI: 0.0488
hipred: Y
hipred_score: 0.504
ghis: 0.401

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.797

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pex26
Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype;

Gene ontology

Biological process: protein targeting to peroxisome;protein import into peroxisome matrix;protein import into peroxisome membrane
Cellular component: peroxisome;peroxisomal membrane;integral component of peroxisomal membrane
Molecular function: protein binding;protein C-terminus binding;protein-containing complex binding;ATPase binding