PEX14

peroxisomal biogenesis factor 14, the group of Peroxins

Basic information

Region (hg38): 1:10472288-10630758

Links

ENSG00000142655 ∙ NCBI:5195 ∙ OMIM:601791 ∙ HGNC:8856 ∙ Uniprot:O75381 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 13A (Zellweger) (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder 13A (Zellweger) (Moderate), mode of inheritance: AR
• peroxisome biogenesis disorder 13A (Zellweger) (Definitive), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), 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 factor disorder 14; 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	15146459; 18285423; 21686775

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX14 gene.

• Peroxisome biogenesis disorder, complementation group K (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX14 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	90	5	97
missense			160	5	1	166
nonsense	1					1
start loss						0
frameshift			2			2
inframe indel			8			8
splice donor/acceptor (+/-2bp)		4				4
splice region			10	16		26
non coding			13	78	18	109
Total	1	4	185	173	24

Variants in PEX14

This is a list of pathogenic ClinVar variants found in the PEX14 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-10472344-G-A		not specified	Uncertain significance (Mar 16, 2022)
1-10472374-G-C		not specified	Uncertain significance (Apr 04, 2024)
1-10472439-G-A		not specified	Uncertain significance (Mar 20, 2024)
1-10474698-C-A			Benign (Dec 18, 2019)
1-10474780-C-G			Benign (Aug 19, 2020)
1-10474957-C-T		PEX14-related disorder	Likely benign (Sep 27, 2023)
1-10474958-C-T		PEX14-related disorder	Likely benign (May 08, 2023)
1-10474960-C-T		PEX14-related disorder	Uncertain significance (May 02, 2017)
1-10474970-GC-TT		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Jul 07, 2023)
1-10474975-C-T		Peroxisome biogenesis disorder, complementation group K	Likely benign (Jan 02, 2024)
1-10474978-G-A		Peroxisome biogenesis disorder, complementation group K	Likely benign (Mar 14, 2023)
1-10474980-A-G		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Jun 27, 2022)
1-10474981-G-A		Peroxisome biogenesis disorder, complementation group K	Likely benign (Feb 13, 2023)
1-10474982-C-G		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Aug 05, 2022)
1-10474984-G-C		Peroxisome biogenesis disorder, complementation group K • Inborn genetic diseases • PEX14-related disorder • Peroxisome biogenesis disorder 13A (Zellweger)	Uncertain significance (Mar 01, 2023)
1-10474985-G-A		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Feb 18, 2022)
1-10474986-C-T		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Jul 26, 2021)
1-10474987-A-C			Uncertain significance (Apr 22, 2013)
1-10474988-G-C		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Apr 13, 2022)
1-10474992-A-G		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Dec 02, 2021)
1-10474992-A-T		Peroxisome biogenesis disorder 13A (Zellweger) • Peroxisome biogenesis disorder, complementation group K • PEX14-related disorder	Conflicting classifications of pathogenicity (Jul 25, 2023)
1-10474994-C-T		Peroxisome biogenesis disorder, complementation group K	Uncertain significance (Feb 03, 2022)
1-10474995-C-G		Peroxisome biogenesis disorder, complementation group K • PEX14-related disorder	Conflicting classifications of pathogenicity (Jan 08, 2024)
1-10474996-G-C		Peroxisome biogenesis disorder, complementation group K • PEX14-related disorder	Likely benign (May 30, 2022)
1-10474997-A-G		Peroxisome biogenesis disorder, complementation group K • Inborn genetic diseases	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX14	protein_coding	protein_coding	ENST00000356607	9	158471

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.226	0.774	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	168	221	0.759	0.0000147	2429
Missense in Polyphen		44	69.639	0.63183		755
Synonymous	-0.908	112	100	1.12	0.00000807	742
Loss of Function	3.15	5	20.3	0.246	0.00000102	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.0000358	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Peroxisome membrane protein that is an essential component of the peroxisomal import machinery. Functions as a docking factor for the predominantly cytoplasmic PTS1 receptor (PEX5). Plays a key role for peroxisome movement through a direct interaction with tubulin. {ECO:0000269|PubMed:21525035, ECO:0000269|PubMed:9653144}.
• Disease: DISEASE: Peroxisome biogenesis disorder complementation group K (PBD-CGK) [MIM:614887]: 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:15146459}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 13A (PBD13A) [MIM:614887]: 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:15146459}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);Beta Oxidation of Very Long Chain Fatty Acids;Oxidation of Branched Chain Fatty Acids;Adrenoleukodystrophy, X-linked;Carnitine-acylcarnitine translocase deficiency;Post-translational protein modification;Metabolism of proteins;Peroxisomal protein import;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins (Consensus)

Recessive Scores

• pRec: 0.217

Intolerance Scores

• loftool: 0.372
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.65

Haploinsufficiency Scores

• pHI: 0.233
• hipred: Y
• hipred_score: 0.783
• ghis: 0.548

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pex14
• 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)

Gene ontology

• Biological process: protein targeting to peroxisome;peroxisome organization;protein import into peroxisome matrix;protein import into peroxisome matrix, docking;protein import into peroxisome matrix, translocation;protein ubiquitination;negative regulation of protein binding;microtubule anchoring;peroxisome transport along microtubule;negative regulation of DNA-binding transcription factor activity;protein import into peroxisome matrix, substrate release;negative regulation of transcription, DNA-templated;protein homooligomerization;protein-containing complex assembly;negative regulation of protein homotetramerization
• Cellular component: fibrillar center;nucleus;peroxisome;peroxisomal membrane;membrane;integral component of membrane;protein-containing complex;peroxisomal importomer complex
• Molecular function: transcription corepressor activity;signaling receptor binding;protein binding;microtubule binding;protein N-terminus binding;beta-tubulin binding