PEX12

peroxisomal biogenesis factor 12, the group of Peroxins

Basic information

Region (hg38): 17:35574794-35578863

Links

ENSG00000108733 ∙ NCBI:5193 ∙ OMIM:601758 ∙ HGNC:8854 ∙ Uniprot:O00623 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 3A (Zellweger) (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 3A (Zellweger) (Definitive), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), mode of inheritance: AR
• peroxisome biogenesis disorder type 3B (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 3A (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 3A; Peroxisome biogenesis factor disorder 3B	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	9090384; 9354782; 9632816; 9792857; 14571262; 17041890; 17534573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX12 gene.

• Peroxisome biogenesis disorder 3A (Zellweger) (415 variants)
• not provided (62 variants)
• Peroxisome biogenesis disorder type 3B;Peroxisome biogenesis disorder 3A (Zellweger) (27 variants)
• Peroxisome biogenesis disorder 3A (Zellweger);Peroxisome biogenesis disorder type 3B (24 variants)
• Inborn genetic diseases (17 variants)
• Peroxisome biogenesis disorder (13 variants)
• Peroxisome biogenesis disorder type 3B (8 variants)
• not specified (6 variants)
• Peroxisome biogenesis disorder 1A (Zellweger) (6 variants)
• PEX12-related condition (5 variants)
• Peroxisomal biogenesis disorder 3b (3 variants)
• PEX12-related disorders (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX12 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			2	110	1	113
missense		2	166	2		170
nonsense	9	16				25
start loss		1				1
frameshift	25	24	2			51
inframe indel		2	10			12
splice donor/acceptor (+/-2bp)	3	2		2		7
splice region			4	5		9
non coding			30	17	12	59
Total	37	47	210	131	13

Highest pathogenic variant AF is 0.000243

Variants in PEX12

This is a list of pathogenic ClinVar variants found in the PEX12 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-35574859-C-T		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35574860-A-G		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 12, 2018)
17-35574898-TTAAG-T		Peroxisome biogenesis disorder 1A (Zellweger)	Benign (Jun 14, 2016)
17-35574946-C-G		Peroxisome biogenesis disorder 3A (Zellweger)	Benign (Jan 12, 2018)
17-35574999-T-G		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575001-A-T		Peroxisome biogenesis disorder 3A (Zellweger)	Benign (Jan 12, 2018)
17-35575004-C-T		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 12, 2018)
17-35575005-AATTAG-A		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
17-35575074-C-T		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575146-A-G		Peroxisome biogenesis disorder 3A (Zellweger)	Benign (Jan 13, 2018)
17-35575211-TAA-T		Peroxisome biogenesis disorder 1A (Zellweger)	Likely benign (Jun 14, 2016)
17-35575213-A-T		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 12, 2018)
17-35575229-TAAC-T		Peroxisome biogenesis disorder 1A (Zellweger)	Likely benign (Jun 14, 2016)
17-35575250-T-C		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575262-T-C		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 12, 2018)
17-35575263-T-C		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575265-T-C		Peroxisome biogenesis disorder 3A (Zellweger)	Benign (Jan 13, 2018)
17-35575273-A-C		Peroxisome biogenesis disorder 3A (Zellweger)	Likely benign (Jan 13, 2018)
17-35575308-T-C		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575349-A-G		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 12, 2018)
17-35575371-T-G		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575402-C-G		Peroxisome biogenesis disorder 3A (Zellweger)	Uncertain significance (Jan 13, 2018)
17-35575447-A-G		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
17-35575485-A-G		Peroxisome biogenesis disorder 3A (Zellweger)	Benign (Jan 12, 2018)
17-35575616-G-T		Peroxisome biogenesis disorder 3A (Zellweger)	Benign (Oct 17, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX12	protein_coding	protein_coding	ENST00000225873	3	4069

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.48e-16	0.00137	124959	10	779	125748	0.00314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.459	161	178	0.903	0.00000891	2314
Missense in Polyphen		62	76.452	0.81097		999
Synonymous	-0.284	70	67.0	1.04	0.00000308	748
Loss of Function	-1.23	20	14.9	1.34	8.62e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0395	0.0392
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000727	0.000721
Middle Eastern	0.000163	0.000163
South Asian	0.000457	0.000457
Other	0.00164	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for protein import into peroxisomes. {ECO:0000269|PubMed:9632816}.
• Disease: DISEASE: Peroxisome biogenesis disorder complementation group 3 (PBD-CG3) [MIM:614859]: 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 3A (PBD3A) [MIM:614859]: 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:9090384}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 3B (PBD3B) [MIM:266510]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry. {ECO:0000269|PubMed:10562279, ECO:0000269|PubMed:19105186}.
• 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: 0.177

Intolerance Scores

• loftool: 0.491
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.73

Haploinsufficiency Scores

• pHI: 0.251
• hipred: N
• hipred_score: 0.480
• ghis: 0.416

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.299

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex12

Gene ontology

• Biological process: protein monoubiquitination;protein targeting to peroxisome;peroxisome organization;protein import into peroxisome matrix;protein ubiquitination
• Cellular component: peroxisome;peroxisomal membrane;integral component of peroxisomal membrane;peroxisomal importomer complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;protein C-terminus binding;zinc ion binding