PEX1
peroxisomal biogenesis factor 1, the group of AAA ATPases|Peroxins
Basic information
Region (hg38): 7:92487020-92528520
Previous symbols: [ "ZWS1", "ZWS" ]
Links
Phenotypes
GenCC
Source:
- peroxisome biogenesis disorder 1A (Zellweger) (Definitive), mode of inheritance: AR
- Heimler syndrome 1 (Strong), mode of inheritance: AR
- Heimler syndrome 1 (Moderate), mode of inheritance: AR
- peroxisome biogenesis disorder 1A (Zellweger) (Definitive), mode of inheritance: AR
- peroxisome biogenesis disorder 1B (Moderate), mode of inheritance: AR
- peroxisome biogenesis disorder 1A (Zellweger) (Definitive), mode of inheritance: AR
- Zellweger spectrum disorders (Supportive), mode of inheritance: AR
- peroxisome biogenesis disorder 1B (Strong), mode of inheritance: AR
- peroxisome biogenesis disorder (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Heimler syndrome 1 | AR | Audiologic/Otolaryngologic | Heimler syndrome 1, 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; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 2063923; 10636745; 9398848; 9398847; 9817926; 9539740; 10447258; 11389485; 12402331; 12032265; 15098231; 16086329; 16088892; 16141001; 20212125; 21844578; 21862673; 22378672; 26387595 |
ClinVar
This is a list of variants' phenotypes submitted to
- Zellweger spectrum disorders (103 variants)
- Heimler syndrome 1 (24 variants)
- not provided (15 variants)
- Peroxisome biogenesis disorder 1A (Zellweger) (13 variants)
- Peroxisome biogenesis disorder (11 variants)
- Peroxisome biogenesis disorder 1B (4 variants)
- PEX1-related disorder (4 variants)
- Peroxisome biogenesis disorder 1B;Peroxisome biogenesis disorder 1A (Zellweger) (3 variants)
- Peroxisome biogenesis disorder 1A (Zellweger);Peroxisome biogenesis disorder 1B (3 variants)
- Inborn genetic diseases (2 variants)
- Heimler syndrome 1;Peroxisome biogenesis disorder 1B;Peroxisome biogenesis disorder 1A (Zellweger) (2 variants)
- Retinal dystrophy (2 variants)
- Abnormality of metabolism/homeostasis (1 variants)
- not specified (1 variants)
- Peroxisomal disorder (1 variants)
- See cases (1 variants)
- Peroxisome biogenesis disorder type 1A (1 variants)
- Peroxisome biogenesis disorder 1B;Peroxisome biogenesis disorder 1A (Zellweger);Heimler syndrome 1 (1 variants)
- Peroxisome biogenesis disorder due to PEX1 defect (1 variants)
- Leber congenital amaurosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX1 gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 440 | 451 | |||
| missense | 11 | 434 | 17 | 465 | ||
| nonsense | 36 | 63 | 100 | |||
| start loss | 6 | |||||
| frameshift | 63 | 133 | 201 | |||
| inframe indel | 21 | 25 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 57 | 71 | |||
| splice region | 26 | 82 | 5 | 113 | ||
| non coding | 20 | 216 | 41 | 278 | ||
| Total | 116 | 270 | 494 | 673 | 44 |
Highest pathogenic variant AF is 0.000506
Variants in PEX1
This is a list of pathogenic ClinVar variants found in the PEX1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-92487029-T-C | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 7-92487165-C-T | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 7-92487216-A-G | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 7-92487221-G-T | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 7-92487223-A-G | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 7-92487277-T-C | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 7-92487324-C-G | Peroxisome biogenesis disorder 1A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 7-92487458-T-C | Zellweger spectrum disorders | Likely benign (Apr 22, 2023) | ||
| 7-92487463-T-C | Zellweger spectrum disorders | Likely benign (Feb 03, 2022) | ||
| 7-92487468-T-C | Inborn genetic diseases | Uncertain significance (Jan 09, 2024) | ||
| 7-92487469-T-C | Zellweger spectrum disorders | Likely benign (Dec 20, 2019) | ||
| 7-92487470-A-T | Zellweger spectrum disorders | Uncertain significance (Oct 13, 2022) | ||
| 7-92487475-C-CT | not specified | Uncertain significance (Aug 01, 2022) | ||
| 7-92487477-G-T | Zellweger spectrum disorders | Uncertain significance (Oct 11, 2023) | ||
| 7-92487481-A-T | Zellweger spectrum disorders | Likely benign (Feb 22, 2023) | ||
| 7-92487485-C-T | Zellweger spectrum disorders | Conflicting classifications of pathogenicity (Oct 14, 2023) | ||
| 7-92487486-G-A | Peroxisome biogenesis disorder 1A (Zellweger) • Zellweger spectrum disorders • not specified | Uncertain significance (Aug 15, 2022) | ||
| 7-92487493-T-C | Zellweger spectrum disorders | Likely benign (Dec 31, 2022) | ||
| 7-92487499-A-T | not specified • Peroxisome biogenesis disorder 1A (Zellweger) • Zellweger spectrum disorders • PEX1-related disorder | Conflicting classifications of pathogenicity (Jan 27, 2024) | ||
| 7-92487501-T-G | Zellweger spectrum disorders | Uncertain significance (Sep 23, 2022) | ||
| 7-92487500-C-CTT | Peroxisome biogenesis disorder 1A (Zellweger) • Zellweger spectrum disorders | Uncertain significance (Mar 03, 2022) | ||
| 7-92487505-A-AT | Zellweger spectrum disorders | Uncertain significance (Aug 19, 2022) | ||
| 7-92487508-T-C | Zellweger spectrum disorders | Likely benign (Nov 15, 2023) | ||
| 7-92487517-C-T | Zellweger spectrum disorders | Likely benign (Mar 07, 2021) | ||
| 7-92487521-G-A | Inborn genetic diseases | Uncertain significance (Apr 01, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PEX1 | protein_coding | protein_coding | ENST00000248633 | 24 | 41512 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.06e-14 | 1.00 | 125499 | 0 | 249 | 125748 | 0.000991 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.14 | 582 | 664 | 0.876 | 0.0000331 | 8352 |
| Missense in Polyphen | 126 | 160.52 | 0.78493 | 1985 | ||
| Synonymous | 0.960 | 220 | 239 | 0.921 | 0.0000119 | 2498 |
| Loss of Function | 3.86 | 35 | 69.8 | 0.501 | 0.00000380 | 802 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00153 | 0.00153 |
| Ashkenazi Jewish | 0.000299 | 0.000298 |
| East Asian | 0.000435 | 0.000435 |
| Finnish | 0.0000925 | 0.0000924 |
| European (Non-Finnish) | 0.00153 | 0.00152 |
| Middle Eastern | 0.000435 | 0.000435 |
| South Asian | 0.000733 | 0.000719 |
| Other | 0.000654 | 0.000652 |
dbNSFP
Source:
- Function
- FUNCTION: Required for stability of PEX5 and protein import into the peroxisome matrix. 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 complementation group 1 (PBD-CG1) [MIM:214100]: A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). {ECO:0000269|PubMed:19105186}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 1A (PBD1A) [MIM:214100]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD1A is an autosomal recessive systemic disorder characterized clinically 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:9398847, ECO:0000269|PubMed:9398848, ECO:0000269|PubMed:9539740}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 1B (PBD1B) [MIM:601539]: 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:11439091, ECO:0000269|PubMed:16088892, ECO:0000269|PubMed:9398847, ECO:0000269|PubMed:9539740}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Heimler syndrome 1 (HMLR1) [MIM:234580]: 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: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)
Intolerance Scores
- loftool
- 0.0841
- rvis_EVS
- -0.19
- rvis_percentile_EVS
- 39.31
Haploinsufficiency Scores
- pHI
- 0.571
- hipred
- Y
- hipred_score
- 0.542
- ghis
- 0.585
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.934
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pex1
- Phenotype
- digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye 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); liver/biliary system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- protein targeting to peroxisome;peroxisome organization;protein import into peroxisome matrix;microtubule-based peroxisome localization
- Cellular component
- cytoplasm;peroxisome;peroxisomal membrane;cytosol;extracellular exosome
- Molecular function
- protein binding;ATP binding;protein C-terminus binding;ATPase activity;ATPase activity, coupled;protein-containing complex binding