PEX2

peroxisomal biogenesis factor 2, the group of Peroxins|Ring finger proteins

Basic information

Region (hg38): 8:76980258-77001044

Previous symbols: [ "PXMP3" ]

Links

ENSG00000164751 ∙ NCBI:5828 ∙ OMIM:170993 ∙ HGNC:9717 ∙ Uniprot:P28328 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 5A (Zellweger) (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 5B (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder 5A (Zellweger) (Definitive), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), mode of inheritance: AR
• peroxisome biogenesis disorder 5B (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 5B (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peroxisome biogenesis disorder 5A; Peroxisome biogenesis disorder 5B	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	1546315; 7541833; 10528859; 14630978; 17041890; 21392394

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX2 gene.

• Peroxisome biogenesis disorder 5A (Zellweger) (29 variants)
• not provided (3 variants)
• Zellweger spectrum disorders (3 variants)
• Peroxisome biogenesis disorder (3 variants)
• Peroxisome biogenesis disorder 5B (1 variants)
• Peroxisome biogenesis disorder 5A (Zellweger);Peroxisome biogenesis disorder 5B (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX2 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			3	123	1	127
missense		2	155	1	2	160
nonsense	12	10	1			23
start loss						0
frameshift	19	30	1			50
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			61	13	17	91
Total	31	42	225	137	20

Highest pathogenic variant AF is 0.0000854

Variants in PEX2

This is a list of pathogenic ClinVar variants found in the PEX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-76980288-A-G		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 12, 2018)
8-76980338-CCTT-C		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
8-76980367-A-G		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76980474-C-T		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 12, 2018)
8-76980561-C-A		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76980598-A-T		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 12, 2018)
8-76980707-C-T		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 13, 2018)
8-76980742-C-T		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76980743-G-A		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76980795-T-C		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 12, 2018)
8-76980805-G-A		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76980815-G-A		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 13, 2018)
8-76980818-T-C		Peroxisome biogenesis disorder 5A (Zellweger)	Likely benign (Jan 12, 2018)
8-76980831-A-G		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76980857-T-C		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Mar 02, 2018)
8-76980884-T-C		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 13, 2018)
8-76980923-G-A		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 13, 2018)
8-76980955-T-C		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 13, 2018)
8-76980967-G-C		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76981119-T-C		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 12, 2018)
8-76981204-C-T		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 12, 2018)
8-76981254-T-A		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 13, 2018)
8-76981257-G-A		Peroxisome biogenesis disorder 5A (Zellweger)	Likely benign (Apr 27, 2017)
8-76981352-C-A		Peroxisome biogenesis disorder 5A (Zellweger)	Benign (Jan 13, 2018)
8-76981403-C-T		Peroxisome biogenesis disorder 5A (Zellweger)	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX2	protein_coding	protein_coding	ENST00000419564	1	20787

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000259	0.790	125674	0	71	125745	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0473	152	154	0.989	0.00000746	2000
Missense in Polyphen		46	46.31	0.99331		637
Synonymous	0.919	49	57.9	0.846	0.00000289	578
Loss of Function	1.11	7	11.0	0.638	6.33e-7	137

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000242
Ashkenazi Jewish	0.00238	0.00238
East Asian	0.000217	0.000217
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000217	0.000217
South Asian	0.000262	0.000261
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Somewhat implicated in the biogenesis of peroxisomes.
• Disease: DISEASE: Peroxisome biogenesis disorder complementation group 5 (PBD-CG5) [MIM:614866]: 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). Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 5A (PBD5A) [MIM:614866]: 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:1546315}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 5B (PBD5B) [MIM:614867]: 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:10528859}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;Peroxisomal protein import;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins (Consensus)

Recessive Scores

• pRec: 0.246

Intolerance Scores

• loftool: 0.162
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.15

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.568
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex2
• 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; skeleton phenotype; renal/urinary system 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); craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: very long-chain fatty acid metabolic process;negative regulation of transcription by RNA polymerase II;protein targeting to peroxisome;fatty acid beta-oxidation;peroxisome organization;protein import into peroxisome matrix;protein ubiquitination;protein destabilization;negative regulation of fibroblast proliferation;negative regulation of epithelial cell proliferation
• Cellular component: peroxisomal membrane;integral component of peroxisomal membrane;membrane;Cdc73/Paf1 complex
• Molecular function: protein binding;metal ion binding