JUP
protein-codingjunction plakoglobin, the group of Beta catenins|Armadillo repeat containing
Gene summary
This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]
- CTNNG
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011017
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011017
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0011017
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0012684
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0012684
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0019276
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0011017
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011017
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0012323
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Dermatologic
Intervention: Cardiovascular
Rationale: 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
Comments: Dermatologic findings may be apparent in Naxos disease, but cardiac association may not be readily appreciated
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to JUP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002230.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 9 | 403 | 3 | 416 | |
| missense | 1 | 661 | 86 | 1 | 749 | |
| nonsense | 11 | 4 | 1 | 16 | ||
| start loss | 2 | 2 | ||||
| frameshift | 15 | 8 | 3 | 26 | ||
| splice donor/acceptor (+/-2bp) | 1 | 4 | 7 | 12 | ||
| Total | 27 | 18 | 683 | 489 | 4 | 1221 |
Highest pathogenic variant AF is 0.000023257819
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002221.1 | 13 | MANE Select | |
| Ensembl | ENSP00000377508.3 | 13 | MANE Select | |
| RefSeq | NP_001339702.1 | 13 | Standard | |
| RefSeq | NP_001339703.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| jupa | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- positive regulation of cell-matrix adhesion
- desmosome assembly
- cytoskeletal anchoring at plasma membrane
- cell migration
- keratinization
Molecular Function
- transcription coactivator activity
- structural molecule activity
- structural constituent of cell wall
- protein binding
- protein kinase binding
Cellular Component
- cornified envelope
- extracellular region
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393931
- Coding exons
- 13
- Length
- 167492
- Individuals with no LoFs
- 125707
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125748
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 398 | 480 | 0.830 | 0.0000326 | 4803 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00037 | 0.00035 | rare |
| Ashkenazi Jewish | 0.00021 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00011 | 0.000092 | rare |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- LoFtool
- 0.752
- RVIS EVS
- -1.66
- RVIS percentile EVS
- 2.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.943
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |