JUP

junction plakoglobin, the group of Beta catenins|Armadillo repeat containing

Basic information

Region (hg38): 17:41754604-41786931

Previous symbols: [ "CTNNG" ]

Links

ENSG00000173801 ∙ NCBI:3728 ∙ OMIM:173325 ∙ HGNC:6207 ∙ Uniprot:P14923 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• arrhythmogenic right ventricular cardiomyopathy (Definitive), mode of inheritance: AD
• inherited epidermolysis bullosa (Strong), mode of inheritance: AR
• Naxos disease (Strong), mode of inheritance: AR
• arrhythmogenic right ventricular dysplasia 12 (Strong), mode of inheritance: AD
• Naxos disease (Strong), mode of inheritance: AR
• Naxos disease (Supportive), mode of inheritance: AR
• lethal acantholytic epidermolysis bullosa (Supportive), mode of inheritance: AR
• Naxos disease (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arrhythmogenic right ventricular dysplasia, familial, 12; Naxos disease	AD/AR	Cardiovascular	Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation	Cardiovascular; Dermatologic	2945574; 10902626; 17924338; 20301310; 22527912; 24460197
Dermatologic findings may be apparent in Naxos disease, but cardiac association may not be readily appreciated

ClinVar

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

• Naxos_disease (1157 variants)
• Arrhythmogenic_right_ventricular_dysplasia_12 (1153 variants)
• Cardiovascular_phenotype (655 variants)
• not_provided (262 variants)
• not_specified (189 variants)
• Cardiomyopathy (55 variants)
• JUP-related_disorder (36 variants)
• Arrhythmogenic_right_ventricular_cardiomyopathy (11 variants)
• Primary_dilated_cardiomyopathy (10 variants)
• Cardiac_arrhythmia (4 variants)
• Primary_familial_hypertrophic_cardiomyopathy (4 variants)
• Wolff-Parkinson-White_pattern (3 variants)
• Hypertrophic_cardiomyopathy (3 variants)
• Long_QT_syndrome (2 variants)
• Ventricular_fibrillation,_paroxysmal_familial,_type_1 (2 variants)
• Palmoplantar_keratodermas (1 variants)
• Conduction_disorder_of_the_heart (1 variants)
• Left_ventricular_noncompaction_cardiomyopathy (1 variants)
• Left_ventricular_noncompaction (1 variants)
• Left_ventricular_hypertrophy (1 variants)
• Left_ventricular_noncompaction_1 (1 variants)
• See_cases (1 variants)
• non-syndromic_arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)
• Primary_familial_dilated_cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JUP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002230.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	9	395	3	408
missense		1	656	83	2	742
nonsense	11	4	1			16
start loss			2			2
frameshift	15	8	3			26
splice donor/acceptor (+/-2bp)	1	4	6			11
Total	27	18	677	478	5

Highest pathogenic variant AF is 0.000023257819

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JUP	protein_coding	protein_coding	ENST00000393931	13	167492

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	398	480	0.830	0.0000326	4803
Missense in Polyphen		120	159.58	0.75198		1619
Synonymous	0.00374	213	213	1.00	0.0000159	1540
Loss of Function	3.33	11	31.0	0.355	0.00000143	339

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000553	0.000553
Ashkenazi Jewish	0.000207	0.000198
East Asian	0.000112	0.000109
Finnish	0.000109	0.0000924
European (Non-Finnish)	0.000127	0.000123
Middle Eastern	0.000112	0.000109
South Asian	0.000200	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Common junctional plaque protein. The membrane- associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE- cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). {ECO:0000250}.
• Disease: DISEASE: Naxos disease (NXD) [MIM:601214]: An autosomal recessive disorder characterized by the association of diffuse non- epidermolytic palmoplantar keratoderma with woolly hair and cardiac abnormalities such as dilated cardiomyopathy and arrhythmogenic right ventricular dysplasia. {ECO:0000269|PubMed:10902626}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 12 (ARVD12) [MIM:611528]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269|PubMed:17924338, ECO:0000269|PubMed:20031617}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric cancer - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Arrhythmogenic Right Ventricular Cardiomyopathy;Corticotropin-releasing hormone signaling pathway;Ectoderm Differentiation;EMT transition in Colorectal Cancer;Keratinization;Developmental Biology;Neutrophil degranulation;Signal Transduction;VEGFA-VEGFR2 Pathway;Innate Immune System;Immune System;EGFR1;E-cadherin signaling in keratinocytes;Posttranslational regulation of adherens junction stability and dissassembly;Signaling by VEGF;Wnt;Cell-cell junction organization;Adherens junctions interactions;Cell junction organization;Signaling by Receptor Tyrosine Kinases;Cell-Cell communication;N-cadherin signaling events;Formation of the cornified envelope;E-cadherin signaling in the nascent adherens junction;VEGFR2 mediated vascular permeability (Consensus)

Recessive Scores

• pRec: 0.338

Intolerance Scores

• loftool: 0.752
• rvis_EVS: -1.66
• rvis_percentile_EVS: 2.74

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: jupa
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: positive regulation of cell-matrix adhesion;desmosome assembly;cytoskeletal anchoring at plasma membrane;cell migration;keratinization;adherens junction organization;regulation of cell population proliferation;positive regulation of protein import into nucleus;neutrophil degranulation;negative regulation of blood vessel endothelial cell migration;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;detection of mechanical stimulus;positive regulation of DNA-binding transcription factor activity;protein heterooligomerization;cornification;endothelial cell-cell adhesion;cellular response to indole-3-methanol;protein localization to plasma membrane;bundle of His cell-Purkinje myocyte adhesion involved in cell communication;regulation of heart rate by cardiac conduction;positive regulation of canonical Wnt signaling pathway;cell-cell adhesion;regulation of ventricular cardiac muscle cell action potential
• Cellular component: cornified envelope;extracellular region;nucleus;cytoplasm;cytosol;cytoskeleton;intermediate filament;plasma membrane;cell-cell junction;cell-cell adherens junction;zonula adherens;fascia adherens;focal adhesion;cytoplasmic side of plasma membrane;intercalated disc;actin cytoskeleton;apicolateral plasma membrane;lateral plasma membrane;catenin complex;Z disc;hemidesmosome;desmosome;protein-DNA complex;specific granule lumen;extracellular exosome;gamma-catenin-TCF7L2 complex;ficolin-1-rich granule lumen
• Molecular function: transcription coactivator activity;structural molecule activity;structural constituent of cell wall;protein binding;protein kinase binding;protein phosphatase binding;nuclear hormone receptor binding;protein homodimerization activity;alpha-catenin binding;cadherin binding;cell adhesion molecule binding;cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication