PEX7

peroxisomal biogenesis factor 7, the group of WD repeat domain containing|Peroxins

Basic information

Region (hg38): 6:136822564-136913934

Links

ENSG00000112357 ∙ NCBI:5191 ∙ OMIM:601757 ∙ HGNC:8860 ∙ Uniprot:O00628 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• rhizomelic chondrodysplasia punctata type 1 (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 9B (Moderate), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 1 (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 9B (Definitive), mode of inheritance: AR
• adult Refsum disease (Supportive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 1 (Definitive), mode of inheritance: AR
• rhizomelic chondrodysplasia punctata type 1 (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder 9B (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
Refsum disease	AR	Biochemical	Dietary measures (eg, phytanic acid restriction, high calorie diet) can help with dermatologic and neurologic manifestations; Surveillance and medical carefor cardiac arrhythmias and cardiomyopathy can reduce morbidity/mortality; Plasmapheresis/lipid apheresis may be used; Fasting and ibuprofen should be avoided	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	18140089; 13045168; 4159604; 85164; 6160883; 2452736; 7541833; 9090381; 9090382; 9090383; 12325024; 11781871; 12522768; 14974078; 17325280; 20301527; 23352163

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX7 gene.

• Peroxisome biogenesis disorder 9B (35 variants)
• Rhizomelic chondrodysplasia punctata type 1 (9 variants)
• not provided (5 variants)
• Rhizomelic chondrodysplasia punctata (3 variants)
• PEX7-related disorder (3 variants)
• Peroxisome biogenesis disorder 9B;Rhizomelic chondrodysplasia punctata type 1;Phytanic acid storage disease (3 variants)
• Peroxisome biogenesis disorder 9B;Rhizomelic chondrodysplasia punctata type 1 (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX7 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			1	148		149
missense	1	9	137	2		149
nonsense	6	19	1			26
start loss						0
frameshift	24	26	3			53
inframe indel	1	1	3			5
splice donor/acceptor (+/-2bp)	5	21	1			27
splice region			10	33	5	48
non coding		1	13	101	24	139
Total	37	77	159	251	24

Highest pathogenic variant AF is 0.000447

Variants in PEX7

This is a list of pathogenic ClinVar variants found in the PEX7 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-136822571-T-C		Peroxisome biogenesis disorder 9B • Rhizomelic chondrodysplasia punctata type 1	Benign (Jul 10, 2021)
6-136822575-G-A		Rhizomelic chondrodysplasia punctata • Phytanic acid storage disease	Uncertain significance (Jun 14, 2016)
6-136822578-T-C		Phytanic acid storage disease • Rhizomelic chondrodysplasia punctata	Uncertain significance (Jun 14, 2016)
6-136822589-T-C		Phytanic acid storage disease • Rhizomelic chondrodysplasia punctata	Uncertain significance (Jun 14, 2016)
6-136822597-C-A		Rhizomelic chondrodysplasia punctata type 1 • Peroxisome biogenesis disorder 9B	Uncertain significance (Apr 27, 2017)
6-136822601-A-T		Rhizomelic chondrodysplasia punctata type 1 • Peroxisome biogenesis disorder 9B	Benign/Likely benign (Aug 14, 2018)
6-136822610-C-T		Peroxisome biogenesis disorder 9B • Rhizomelic chondrodysplasia punctata type 1 • Rhizomelic chondrodysplasia punctata	Benign (Jun 14, 2018)
6-136822619-A-AACGGCTTCC		Rhizomelic chondrodysplasia punctata type 1	Uncertain significance (Apr 30, 2018)
6-136822621-C-T		Phytanic acid storage disease • Peroxisome biogenesis disorder 9B	Likely pathogenic (Jan 24, 2024)
6-136822622-G-A		not specified	Likely benign (Sep 08, 2017)
6-136822631-G-A		Peroxisome biogenesis disorder 9B • Rhizomelic chondrodysplasia punctata type 1	Uncertain significance (Jan 13, 2018)
6-136822635-G-A		not specified • Peroxisome biogenesis disorder 9B • Rhizomelic chondrodysplasia punctata type 1 • Rhizomelic chondrodysplasia punctata	Benign/Likely benign (Apr 27, 2017)
6-136822638-G-A		Rhizomelic chondrodysplasia punctata type 1 • Peroxisome biogenesis disorder 9B	Uncertain significance (Jan 13, 2018)
6-136822648-C-T		Rhizomelic chondrodysplasia punctata type 1 • Peroxisome biogenesis disorder 9B	Uncertain significance (Jan 13, 2018)
6-136822656-G-T		PEX7-related disorder	Likely benign (Jul 22, 2019)
6-136822663-G-A		Peroxisome biogenesis disorder 9B • Rhizomelic chondrodysplasia punctata type 1	Uncertain significance (Jan 12, 2018)
6-136822664-G-A			Uncertain significance (May 08, 2024)
6-136822665-G-A		not specified	Uncertain significance (Aug 02, 2023)
6-136822669-A-AGTGCGGT		Peroxisome biogenesis disorder 9B • Rhizomelic chondrodysplasia punctata type 1 • Rhizomelic chondrodysplasia punctata	Pathogenic/Likely pathogenic (Mar 26, 2024)
6-136822673-CG-C		Peroxisome biogenesis disorder 9B	Pathogenic (Jul 25, 2023)
6-136822674-G-A		Peroxisome biogenesis disorder 9B	Likely benign (Dec 14, 2023)
6-136822674-G-C		Peroxisome biogenesis disorder 9B	Likely benign (Jan 31, 2024)
6-136822676-TG-T		Peroxisome biogenesis disorder 9B	Pathogenic (Dec 14, 2023)
6-136822677-G-A		Peroxisome biogenesis disorder 9B	Likely benign (Jul 03, 2023)
6-136822680-C-T		Peroxisome biogenesis disorder 9B	Likely benign (Jul 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX7	protein_coding	protein_coding	ENST00000318471	10	91359

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.18e-13	0.0377	125601	0	147	125748	0.000585

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.497	145	163	0.890	0.00000774	2096
Missense in Polyphen		50	50.659	0.98699		674
Synonymous	-0.747	71	63.4	1.12	0.00000351	621
Loss of Function	0.142	19	19.7	0.966	9.40e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000810	0.000810
Ashkenazi Jewish	0.00	0.00
East Asian	0.000761	0.000761
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000933	0.000932
Middle Eastern	0.000761	0.000761
South Asian	0.000131	0.000131
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the N-terminal PTS2-type peroxisomal targeting signal and plays an essential role in peroxisomal protein import.
• Disease: DISEASE: Rhizomelic chondrodysplasia punctata 1 (RCDP1) [MIM:215100]: A peroxisome biogenesis disorder. It is 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:9090381}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 9B (PBD9B) [MIM:614879]: A peroxisome biogenesis disorder with unusually mild clinical and biochemical manifestations. Affected individuals manifest a variable phenotype similar to, and in some cases indistinguishable from, classic Refsum disease. Variable features include ocular abnormalities, sensorimotor neuropathy, ichthyosis, deafness, chondrodysplasia punctata without rhizomelia or growth failure. {ECO:0000269|PubMed:12522768}. 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: 0.200

Intolerance Scores

• loftool: 0.616
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.113
• hipred: N
• hipred_score: 0.335
• ghis: 0.519

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.584

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex7
• 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; immune system phenotype; skeleton phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: neuron migration;endochondral ossification;protein targeting to peroxisome;fatty acid beta-oxidation;peroxisome organization;ether lipid biosynthetic process;protein import into peroxisome matrix
• Cellular component: peroxisome;peroxisomal membrane;peroxisomal matrix;cytosol
• Molecular function: peroxisome matrix targeting signal-2 binding;protein binding;enzyme binding;protein homodimerization activity