PEX5

peroxisomal biogenesis factor 5, the group of Peroxins|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 12:7188685-7218574

Previous symbols: [ "PXR1" ]

Links

ENSG00000139197 ∙ NCBI:5830 ∙ OMIM:600414 ∙ HGNC:9719 ∙ Uniprot:P50542 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 1A (Zellweger) (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 2A (Zellweger) (Moderate), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 5 (Limited), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 5 (Supportive), mode of inheritance: AR
• peroxisome biogenesis disorder 2B (Definitive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 5 (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder 2A (Zellweger) (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 2A (Zellweger syndrome); Peroxisome biogenesis disorder 2B; Rhizomelic chondrodysplasia punctata, type 5	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	7719337; 26220973

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX5 gene.

• Peroxisome biogenesis disorder 2B (37 variants)
• not provided (3 variants)
• Rhizomelic chondrodysplasia punctata (1 variants)
• Rhizomelic chondrodysplasia punctata type 5 (1 variants)
• Peroxisome biogenesis disorder 2A (Zellweger) (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX5 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			5	199	1	205
missense	1	1	311		3	316
nonsense	15	2	1			18
start loss			1			1
frameshift	23	3	2			28
inframe indel			7			7
splice donor/acceptor (+/-2bp)	1	15	2			18
splice region		1	19	48	1	69
non coding			49	158	56	263
Total	40	21	378	357	60

Highest pathogenic variant AF is 0.0000197

Variants in PEX5

This is a list of pathogenic ClinVar variants found in the PEX5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-7189698-C-T		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7189712-C-G		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7189714-T-C		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 12, 2018)
12-7189718-G-A		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 12, 2018)
12-7189718-G-T		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 12, 2018)
12-7189747-C-G		Peroxisome biogenesis disorder 2A (Zellweger)	Benign (Jan 13, 2018)
12-7189770-G-GGCC		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
12-7189772-GGCCCGGGGCCGCGTCCCT-CC		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
12-7189790-T-C		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7189815-C-G		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 12, 2018)
12-7189821-G-A		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 12, 2018)
12-7189852-G-C		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7189901-G-A		Peroxisome biogenesis disorder 2A (Zellweger)	Likely benign (Jan 12, 2018)
12-7189935-T-C		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7189938-T-C		Peroxisome biogenesis disorder 2A (Zellweger)	Likely benign (Apr 27, 2017)
12-7189979-AG-A		PEX5-related disorder	Uncertain significance (Aug 30, 2024)
12-7189990-G-A		Peroxisome biogenesis disorder 2A (Zellweger) • PEX5-related disorder	Uncertain significance (Jan 12, 2018)
12-7189999-C-T		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7190023-G-T		Peroxisome biogenesis disorder 2A (Zellweger)	Likely benign (Jan 12, 2018)
12-7190040-T-A		Peroxisome biogenesis disorder 2A (Zellweger)	Benign (Dec 24, 2018)
12-7190088-G-A		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 12, 2018)
12-7190213-A-G		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (Jan 13, 2018)
12-7190262-G-A			Benign (Dec 01, 2018)
12-7190373-T-C		Peroxisome biogenesis disorder 2A (Zellweger)	Uncertain significance (May 05, 2020)
12-7190378-A-G		Peroxisome biogenesis disorder 2B	Uncertain significance (Sep 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX5	protein_coding	protein_coding	ENST00000434354	15	29890

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000556	1.00	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.681	325	361	0.899	0.0000226	4231
Missense in Polyphen		71	100.24	0.70832		1293
Synonymous	-0.281	149	145	1.03	0.00000837	1323
Loss of Function	3.51	14	37.1	0.378	0.00000203	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000132	0.000131
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. {ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}.
• Disease: DISEASE: Peroxisome biogenesis disorder 2A (PBD2A) [MIM:214110]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and 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:7719337}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 2B (PBD2B) [MIM:202370]: 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:10462504, ECO:0000269|PubMed:7719337}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Rhizomelic chondrodysplasia punctata 5 (RCDP5) [MIM:616716]: A form of rhizomelic chondrodysplasia punctata, a disease characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe mental retardation with spasticity. {ECO:0000269|PubMed:26220973}. 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: 0.321

Intolerance Scores

• loftool: 0.0644
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.36

Haploinsufficiency Scores

• pHI: 0.519
• hipred: Y
• hipred_score: 0.756
• ghis: 0.552

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.697

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex5
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary 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); reproductive system phenotype; hematopoietic system phenotype; neoplasm; 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); digestive/alimentary phenotype

Gene ontology

• Biological process: protein targeting to peroxisome;protein import into peroxisome matrix;protein import into peroxisome matrix, docking;protein ubiquitination;protein import into peroxisome membrane;negative regulation of protein homotetramerization
• Cellular component: cytoplasm;peroxisome;peroxisomal membrane;Golgi apparatus;cytosol;membrane;protein-containing complex
• Molecular function: peroxisome targeting sequence binding;peroxisome matrix targeting signal-1 binding;protein binding;enzyme binding;small GTPase binding;protein N-terminus binding