JUP

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

Basic information

Region (hg38): 17:41754603-41786931

Previous symbols: [ "CTNNG" ]

Links

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

Phenotypes

GenCC

Source: genCC

• inherited epidermolysis bullosa (Strong), mode of inheritance: AR
• Naxos disease (Strong), mode of inheritance: AR
• Naxos disease (Moderate), mode of inheritance: AR
• Naxos disease (Supportive), mode of inheritance: AR
• lethal acantholytic epidermolysis bullosa (Supportive), mode of inheritance: AR
• arrhythmogenic right ventricular dysplasia 12 (Strong), mode of inheritance: AD
• Naxos disease (Strong), 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;Arrhythmogenic right ventricular dysplasia 12 (558 variants)
• Cardiovascular phenotype (398 variants)
• not provided (239 variants)
• Arrhythmogenic right ventricular dysplasia 12;Naxos disease (206 variants)
• not specified (186 variants)
• Naxos disease (121 variants)
• Arrhythmogenic right ventricular dysplasia 12 (115 variants)
• Cardiomyopathy (59 variants)
• Inborn genetic diseases (16 variants)
• Arrhythmogenic right ventricular cardiomyopathy (11 variants)
• Primary dilated cardiomyopathy (7 variants)
• Primary familial hypertrophic cardiomyopathy (4 variants)
• Cardiac arrhythmia (3 variants)
• JUP-related condition (3 variants)
• Wolff-Parkinson-White pattern (3 variants)
• Left ventricular noncompaction 1 (2 variants)
• Ventricular fibrillation, paroxysmal familial, type 1 (2 variants)
• Left ventricular noncompaction (2 variants)
• Long QT syndrome (2 variants)
• Hypertrophic cardiomyopathy;Cardiomyopathy (2 variants)
• Primary familial dilated cardiomyopathy (1 variants)
• Primary dilated cardiomyopathy;Cardiomyopathy (1 variants)
• Conduction disorder of the heart (1 variants)
• Left ventricular hypertrophy (1 variants)
• Hypertrophic cardiomyopathy (1 variants)
• Left ventricular noncompaction 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.

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			10	213	1	224
missense			441	4	2	447
nonsense	5		2			7
start loss			2			2
frameshift	9	2	3			14
inframe indel			8			8
splice donor/acceptor (+/-2bp)		2	2			4
splice region			20	28	2	50
non coding			28	71	33	132
Total	14	4	496	288	36

Highest pathogenic variant AF is 0.0000131

Variants in JUP

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

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

Position	Type	Phenotype	Significance	ClinVar
17-41754608-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease • Naxos disease;Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Feb 23, 2022)
17-41754717-C-G		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Conflicting classifications of pathogenicity (May 21, 2021)
17-41754718-C-T		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease • Naxos disease;Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Aug 26, 2021)
17-41754730-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 13, 2018)
17-41754838-T-G		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease • Naxos disease;Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Aug 11, 2021)
17-41754891-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Conflicting classifications of pathogenicity (May 18, 2021)
17-41754957-T-C		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 13, 2018)
17-41754973-C-G		Naxos disease • Arrhythmogenic right ventricular dysplasia 12 • Naxos disease;Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Jul 19, 2021)
17-41755016-T-G		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 12, 2018)
17-41755035-C-G		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Benign/Likely benign (May 12, 2021)
17-41755074-C-A		Naxos disease • Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Jan 12, 2018)
17-41755075-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Benign/Likely benign (May 12, 2021)
17-41755121-C-T		Naxos disease • Arrhythmogenic right ventricular dysplasia 12	Conflicting classifications of pathogenicity (May 16, 2021)
17-41755151-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 12, 2018)
17-41755171-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 13, 2018)
17-41755177-G-C		Naxos disease • Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Jan 13, 2018)
17-41755247-T-A		Naxos disease • Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Jan 12, 2018)
17-41755308-C-T		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 12, 2018)
17-41755331-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease • Naxos disease;Arrhythmogenic right ventricular dysplasia 12	Uncertain significance (Sep 08, 2021)
17-41755335-G-C		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 13, 2018)
17-41755393-C-T		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 12, 2018)
17-41755405-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 12, 2018)
17-41755428-C-T		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Uncertain significance (Jan 12, 2018)
17-41755432-C-T		not specified	Likely benign (Mar 03, 2016)
17-41755458-G-A		Arrhythmogenic right ventricular dysplasia 12 • Naxos disease	Benign/Likely benign (Jun 29, 2018)

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
0.000801	0.999	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

Haploinsufficiency Scores

• pHI: 0.990
• hipred: Y
• hipred_score: 0.790
• ghis: 0.601

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

Mouse Genome Informatics

• Gene name: Jup
• 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); normal phenotype; hematopoietic system phenotype; 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); respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; immune system 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); muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

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