PEX6

peroxisomal biogenesis factor 6, the group of Peroxins|AAA ATPases

Basic information

Region (hg38): 6:42963865-42979181

Links

ENSG00000124587 ∙ NCBI:5190 ∙ OMIM:601498 ∙ HGNC:8859 ∙ Uniprot:Q13608 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 4A (Zellweger) (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 4A (Zellweger) (Definitive), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), mode of inheritance: AR
• autosomal recessive cerebellar ataxia-blindness-deafness syndrome (Supportive), mode of inheritance: AR
• peroxisome biogenesis disorder 4B (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 4A (Zellweger) (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder (Definitive), mode of inheritance: AR
• Heimler syndrome 2 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heimler syndrome 2 (Peroxisome biogenesis disorder 4C)	AR	Audiologic/Otolaryngologic	Heimler syndrome 2, representing a mild peroxisomal biogenesis disorder, includes sensorineural hearing loss among other features, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	8940266; 8670792; 10408779; 11355018; 16530715; 17041890; 19877282; 21937992; 22894767; 26387595

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX6 gene.

• Peroxisome_biogenesis_disorder (1541 variants)
• not_provided (212 variants)
• Peroxisome_biogenesis_disorder_4A_(Zellweger) (197 variants)
• Zellweger_spectrum_disorders (191 variants)
• Heimler_syndrome_2 (172 variants)
• Peroxisome_biogenesis_disorder_4B (127 variants)
• Inborn_genetic_diseases (121 variants)
• PEX6-related_disorder (118 variants)
• not_specified (43 variants)
• Peroxisome_biogenesis_disorder_1A_(Zellweger) (5 variants)
• Paroxysmal_dystonia (2 variants)
• Peripheral_neuropathy (2 variants)
• Cognitive_impairment (2 variants)
• Premature_ovarian_insufficiency (2 variants)
• See_cases (2 variants)
• Cerebellar_ataxia (2 variants)
• Retinal_dystrophy (2 variants)
• Sensorineural_hearing_loss_disorder (2 variants)
• CNS_demyelination (1 variants)
• Hypotonia (1 variants)
• Peroxisome_biogenesis_disorder_2B (1 variants)
• Leukodystrophy (1 variants)
• Global_developmental_delay (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Megalencephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000287.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	21	591	3	617
missense	8	42	549	26	1	626
nonsense	28	30				58
start loss	3	3				6
frameshift	67	85	2			154
splice donor/acceptor (+/-2bp)	6	41	3	1		51
Total	113	202	575	618	4

Highest pathogenic variant AF is 0.00308946

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX6	protein_coding	protein_coding	ENST00000304611	17	15351

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000625	1.00	125617	0	131	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	436	529	0.824	0.0000311	6093
Missense in Polyphen		139	183.72	0.75659		2149
Synonymous	0.362	220	227	0.969	0.0000120	2268
Loss of Function	3.21	15	35.7	0.421	0.00000167	443

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000478	0.000478
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000451	0.000323
European (Non-Finnish)	0.000637	0.000633
Middle Eastern	0.000381	0.000381
South Asian	0.00105	0.00105
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in peroxisome biosynthesis. Required for stability of the PTS1 receptor. Anchored by PEX26 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes.
• Disease: DISEASE: Peroxisome biogenesis disorder 4A (PBD4A) [MIM:614862]: 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:10408779, ECO:0000269|PubMed:8670792}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 4B (PBD4B) [MIM:614863]: 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:11355018}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Heimler syndrome 2 (HMLR2) [MIM:616617]: A form of Heimler syndrome, a very mild peroxisome biogenesis disorder characterized by sensorineural hearing loss, amelogenesis imperfecta resulting in enamel hyoplasia of the secondary dentition, nail defects, and occasional or late-onset retinal pigmentation abnormalities. {ECO:0000269|PubMed:19105186, ECO:0000269|PubMed:26387595, ECO:0000269|PubMed:27302843}. 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)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.114
• rvis_EVS: 1.14
• rvis_percentile_EVS: 92.34

Haploinsufficiency Scores

• pHI: 0.366
• hipred: N
• hipred_score: 0.477
• ghis: 0.422

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.452

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex6

Gene ontology

• Biological process: protein targeting to peroxisome;peroxisome organization;protein import into peroxisome matrix;protein import into peroxisome matrix, translocation;protein stabilization
• Cellular component: photoreceptor outer segment;cytoplasm;peroxisome;peroxisomal membrane;cytosol;photoreceptor cell cilium
• Molecular function: protein binding;ATP binding;protein C-terminus binding;ATPase activity;ATPase activity, coupled;protein-containing complex binding