PEX19

peroxisomal biogenesis factor 19, the group of Peroxins

Basic information

Region (hg38): 1:160276806-160286348

Previous symbols: [ "PXF" ]

Links

ENSG00000162735 ∙ NCBI:5824 ∙ OMIM:600279 ∙ HGNC:9713 ∙ Uniprot:P40855 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 1A (Zellweger) (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 12A (Zellweger) (Strong), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), mode of inheritance: AR
• peroxisome biogenesis disorder 12A (Zellweger) (Moderate), mode of inheritance: AR
• peroxisome biogenesis disorder 12A (Zellweger) (Definitive), 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, 19; Zellweger syndrome	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	9727033; 10051604; 20683989

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX19 gene.

• Peroxisome biogenesis disorder 12A (Zellweger) (353 variants)
• not provided (49 variants)
• Inborn genetic diseases (9 variants)
• not specified (8 variants)
• PEX19-related condition (5 variants)
• Peroxisome biogenesis disorder 1A (Zellweger) (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX19 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			4	52		56
missense	1		150			151
nonsense	2	1				3
start loss						0
frameshift	3		2			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)		6	1			7
splice region			4	13		17
non coding			43	45	15	103
Total	6	7	203	97	15

Highest pathogenic variant AF is 0.00000657

Variants in PEX19

This is a list of pathogenic ClinVar variants found in the PEX19 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-160276834-T-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160276914-C-T		Peroxisome biogenesis disorder 12A (Zellweger)	Benign (Jan 12, 2018)
1-160276996-A-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277015-T-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277128-CAG-C		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
1-160277134-G-A		Peroxisome biogenesis disorder 12A (Zellweger)	Benign (Jan 12, 2018)
1-160277138-G-A		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277168-G-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160277198-C-A		Peroxisome biogenesis disorder 12A (Zellweger)	Benign (Jan 12, 2018)
1-160277327-C-A		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277395-G-C		Peroxisome biogenesis disorder 12A (Zellweger)	Benign (Jan 12, 2018)
1-160277396-G-A		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277483-A-G		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160277494-A-C		Peroxisome biogenesis disorder 12A (Zellweger)	Likely benign (Apr 27, 2017)
1-160277571-A-G		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277699-G-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 13, 2018)
1-160277749-C-G		Peroxisome biogenesis disorder 12A (Zellweger)	Likely benign (Jan 13, 2018)
1-160277761-T-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160277790-G-T		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160277806-A-G		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160277959-C-T		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160278080-T-A		Peroxisome biogenesis disorder 12A (Zellweger)	Benign (Apr 27, 2017)
1-160278089-G-C		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160278101-A-T		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)
1-160278216-C-A		Peroxisome biogenesis disorder 12A (Zellweger)	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX19	protein_coding	protein_coding	ENST00000368072	8	9537

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000319	0.950	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.776	190	162	1.17	0.00000837	1984
Missense in Polyphen		51	51.81	0.98437		691
Synonymous	-0.668	70	63.2	1.11	0.00000377	555
Loss of Function	1.75	8	15.4	0.518	6.70e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53. {ECO:0000269|PubMed:10051604, ECO:0000269|PubMed:10704444, ECO:0000269|PubMed:11259404, ECO:0000269|PubMed:11883941, ECO:0000269|PubMed:14709540, ECO:0000269|PubMed:15007061}.
• Disease: DISEASE: Peroxisome biogenesis disorder 12A (PBD12A) [MIM:614886]: 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:10051604}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.255

Intolerance Scores

• loftool: 0.343
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.333
• hipred: Y
• hipred_score: 0.756
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex19

Gene ontology

• Biological process: protein targeting to peroxisome;peroxisome organization;peroxisome fission;protein import into peroxisome membrane;protein stabilization;transmembrane transport;chaperone-mediated protein folding;chaperone-mediated protein transport;establishment of protein localization to peroxisome;negative regulation of lipid binding
• Cellular component: nucleoplasm;cytoplasm;peroxisome;peroxisomal membrane;cytosol;brush border membrane;protein-containing complex
• Molecular function: protein binding;peroxisome membrane class-1 targeting sequence binding;protein N-terminus binding;ATPase binding