PKP2

Summary

PKP2 (plakophilin 2, HGNC:9024) is a protein-coding gene on chromosome 12p11.21, encoding Plakophilin-2 (Q99959). A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This gene may regulate the signaling activity of beta-catenin and is required to maintain transcription of genes that control intracellular calcium cycling including ryanodine receptor 2, ankyrin-B, triadin, and calcium channel, voltage-dependent, L type, alpha 1C. Mutations in this gene are associated with different inherited cardiac conditions including Arrythmogenic Cardiomyopathy, Brugada Syndrome, and Idiopathic Ventricular Fibrillation. A processed pseudogene with high similarity to this gene has been mapped to chromosome 12p13.

Source: NCBI Gene 5318 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arrhythmogenic right ventricular cardiomyopathy (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 2,357 total — 232 pathogenic, 94 likely-pathogenic
• Phenotypes (HPO): 24
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001005242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9024
Approved symbol	PKP2
Name	plakophilin 2
Location	12p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000057294
Ensembl biotype	protein_coding
OMIM	602861
Entrez	5318

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000070846, ENST00000340811, ENST00000546498, ENST00000546741, ENST00000546769, ENST00000549461, ENST00000700555, ENST00000700557, ENST00000700558, ENST00000700559, ENST00000700560, ENST00000700561, ENST00000700562, ENST00000700563, ENST00000700564, ENST00000700565

RefSeq mRNA: 10 — MANE Select: NM_001005242 NM_001005242, NM_001407155, NM_001407156, NM_001407157, NM_001407158, NM_001407159, NM_001407160, NM_001407161, NM_001407162, NM_004572

CCDS: CCDS31771, CCDS8731

Canonical transcript exons

ENST00000340811 — 13 exons

Exon	Start	End
ENSE00001101448	32868927	32869062
ENSE00001133478	32850766	32850973
ENSE00001374889	32896509	32896777
ENSE00002352416	32802403	32802556
ENSE00003980147	32877846	32878543
ENSE00003980150	32796109	32796298
ENSE00003980161	32790755	32792492
ENSE00003980163	32824045	32824162
ENSE00003980164	32792644	32792731
ENSE00003980168	32822467	32822631
ENSE00003980171	32841028	32841205
ENSE00004014197	32821356	32821529
ENSE00004014199	32878920	32879032

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9210 / max 528.4879, expressed in 1013 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130415	10.6824	1009
130409	0.1469	43
130411	0.0356	8
130414	0.0231	8
130412	0.0121	7
130410	0.0115	5
130413	0.0094	5

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	98.52	gold quality
apex of heart	UBERON:0002098	98.31	gold quality
left ventricle myocardium	UBERON:0006566	98.20	gold quality
heart left ventricle	UBERON:0002084	97.59	gold quality
myocardium	UBERON:0002349	97.59	gold quality
cardiac ventricle	UBERON:0002082	97.58	gold quality
right uterine tube	UBERON:0001302	97.01	gold quality
right atrium auricular region	UBERON:0006631	96.93	gold quality
cardiac atrium	UBERON:0002081	96.86	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.45	gold quality
colonic mucosa	UBERON:0000317	96.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.02	gold quality
rectum	UBERON:0001052	95.84	gold quality
heart	UBERON:0000948	94.63	gold quality
mucosa of transverse colon	UBERON:0004991	93.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.05	gold quality
minor salivary gland	UBERON:0001830	91.82	gold quality
saliva-secreting gland	UBERON:0001044	91.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.99	gold quality
germinal epithelium of ovary	UBERON:0001304	88.87	gold quality
parotid gland	UBERON:0001831	88.53	gold quality
jejunal mucosa	UBERON:0000399	88.06	gold quality
mouth mucosa	UBERON:0003729	87.46	gold quality
nasal cavity mucosa	UBERON:0001826	86.89	gold quality
transverse colon	UBERON:0001157	86.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.55	gold quality
colonic epithelium	UBERON:0000397	86.05	gold quality
right ovary	UBERON:0002118	86.02	gold quality
left ovary	UBERON:0002119	85.77	gold quality
islet of Langerhans	UBERON:0000006	85.63	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	331.61
E-MTAB-6701	yes	77.53
E-MTAB-6678	yes	6.61
E-CURD-11	no	93.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, PKP1, PKP3

miRNA regulators (miRDB)

98 targeting PKP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling (PMID:11790773)
• In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. (PMID:15489853)
• mutations in the desmosomal plakophilin-2 gene can cause arrhythmogenic right ventricular cardiomyopathy (PMID:16415378)
• PKP2 mutation in arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C) correlates with earlier onset of symptoms and arrhythmia. Patients experience implanted cardioverter/defibrillator(ICD) interventions irrespective of classic risk factors. (PMID:16549640)
• PKP2 mutations can be identified in nearly half of the Dutch patients fulfilling the arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVC)criteria. (PMID:16567567)
• Premature truncation of the plakophilin-2 protein appears to be the predominant mechanism whereby PKP2 mutations elicit the arrhythmogenic right ventricular cardiomyopathy phenotype. (PMID:16876743)
• PKP2 mutations in a group of families with ARVD/C have both reduced penetrance and variable expressivity. Gender may have an influence on penetrance of PKP2 mutations, with male mutation carriers more likely to develop specific phenotypic manifestations (PMID:17010805)
• Novel homozygous mutation in PKP2 (c.[2484C>T]+[2484C>T]), which is predicted to be translationally silent, produced an alternatively spliced variant and Arrhytmogenic right ventricular dysplasia. (PMID:17041889)
• The present study adds to the growing body of evidence that plakophilin-2 missense mutations represent a major inherited cause of arrhythmogenic right ventricular dysplasia (ARVD) in patients of Finnish ancestry. (PMID:17521752)
• PKP2 knockdown is accompanied by increased phosphorylation of PKC substrates, raising the possibility that global alterations in PKC signaling may contribute to pathogenesis of congenital defects caused by PKP2 deficiency. (PMID:18474624)
• Mutations in the desmosome genes were identified in four of the five patients (three with a DSG2 mutation and one with a DSP mutation). Five gene mutations were noted in four patients and all mutations were novel (one patient had a DSG2 double mutation). (PMID:18632414)
• Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease. (PMID:18662195)
• Their expression did not disrupt localization of endogenous PKP2, connexin-43 (Cx43), or desmoplakin (DP). However, we observed reduced abundance of Cx43 after R79x expression. (PMID:19084810)
• Data discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese Arrhythmogenic right ventricular cardiomyopathy population. (PMID:19302745)
• Direct sequencing of PKP2 led to the identification of 5 novel heterozygous mutations (R158K, Q211X, L419S, A793D, and N852fsX930) in 39% of patients (7 of 18) with ARVD/C. (PMID:19427443)
• Mutant plakophilin-2 proteins were unable to disrupt established desmosomes when expressed in an E-cadherin-expressing epithelial cell model; they were unable to initiate de novo assembly of desmosomes in an N-cadherin-expressing epithelial cell model. (PMID:19533476)
• massive acquisition of Pkp2 and its integration into adherens junctions (AJ) plaques of a large number of transformed cell lines is demonstrated with biochemical and immunolocalization techniques. (PMID:19551809)
• mutations in plakophylin-2 (PKP2) gene in ARVC (PMID:19880068)
• Fifteen percent of Danish arrhythmogenic right ventricular cardiomyopathy/dysplasia patients carried PKP2 mutations. (PMID:19955750)
• Data suggest that PKP2 may functionally link RhoA- and PKC-dependent pathways to drive actin reorganization. (PMID:20554761)
• Adherens junctions connecting cardiac myxoma cells show exactly such general acquisition of Pkp2. (PMID:20693980)
• Studies identified two mutations in DSG2, four in DSC2, two in DSP, four in JUP and seven in PKP2. (PMID:20864495)
• PKP2A was shown to be the major isoform expressed in human heart tissue and PKP2B protein was undetectable; results strongly suggest that p.Arg490Trp and other variants located in PKP2 exon 6 may not be disease causing (PMID:21378009)
• In breast cancer, compared with normal tissue, PKP1 and PKP2 expressions were indifferent (P > 0.05), but PKP3 expression was significantly increased (PMID:21947748)
• PKP2 mutations are not specific for arrhythmogenic right ventricular cardiomyopathy and may result in sudden unexpected death with negative autopsy. (PMID:22019812)
• The authors report on a pedigree of cases involving a mutation in the plakophilin 2 gene that was associated with the development of arrhythmogenic right ventricular cardiomyopathy. (PMID:22035158)
• PKP2 gene upregulation is associated with bladder cancer invasion. (PMID:22119253)
• While many of the reported ARVC mutations are truncating mutations, the possibly damaging variant found in this family, is a missense alteration affecting a highly conserved residue 506 located in exon 7. (PMID:22170284)
• haploinsufficiency is the most likely cause for the genesis of dominant arrhythmogenic right ventricular cardiomyopathy due to mutations in PKP2 (PMID:22781308)
• Results show that PKP2 mutations are insufficient to cause ARVD due to variable expression and incomplete penetrance (PMID:23147395)
• PKP2 gene mutation is associated with arrhythmogenic cardiomyopathy in a large Dutch family. (PMID:23270881)
• The copy number variations analysis identified a heterozygous deletion of about 122 kb on chromosome 12p11.21, including the entire plakophilin-2 gene and shared by all affected family members. (PMID:23486541)
• Of a total of 715 Sudden cardiac death cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W. (PMID:23651034)
• These data uncover a potential role for PKP2 upstream of beta1 integrin and RhoA in integrating cell-cell and cell-substrate contact signaling in basal keratinocytes. (PMID:23884246)
• Downstream Hippo molecules STE20-like protein kinases 1/2, large tumor suppressor kinases 1/2, and Yes-associated protein (YAP, the effector of the pathway) are phosphorylated, offering novel mechanisms for arrhythmogenic cardiomyopathy pathogenesis. (PMID:24276085)
• Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype. (PMID:24352520)
• PKP2 haploinsufficiency contributes to pathogenesis in arrhythmogenic cardiomyopathy. (PMID:24704780)
• mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy (PMID:24967631)
• Six variants of uncertain clinical significance in the PKP2, JUP, and DSG2 genes showed a deleterious effect on mRNA splicing, indicating these are ARVD/C-related pathogenic splice site mutations. (PMID:25087486)
• PKP2 is a novel activator of the EGFR signaling pathway. (PMID:25113560)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkp2	ENSDARG00000023026
mus_musculus	Pkp2	ENSMUSG00000041957
rattus_norvegicus	Pkp2	ENSRNOG00000001825
drosophila_melanogaster	p120ctn	FBGN0260799
caenorhabditis_elegans		WBGENE00002175

Paralogs (6): PKP1 (ENSG00000081277), ARVCF (ENSG00000099889), PKP4 (ENSG00000144283), CTNND2 (ENSG00000169862), PKP3 (ENSG00000184363), CTNND1 (ENSG00000198561)

Protein

Protein identifiers

Plakophilin-2 — Q99959 (reviewed: Q99959)

All UniProt accessions (7): Q99959, A0A087WXY2, A0A8V8TPU9, A0A8V8TQD7, A0AAQ5BGX6, A0AAQ5BGY2, A0AAQ5BH07

UniProt curated annotations — full annotation on UniProt →

Function. A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins. Required to maintain gingival epithelial barrier function. Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction. Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls. Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments. Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling. Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions. Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program. Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation. Binds single-stranded DNA (ssDNA). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart. Involved in the inhibition of viral infection by influenza A viruses (IAV). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins.

Subunit / interactions. Interacts with DSC2. Interacts with JUP. Interacts with KRT5/CK5, KRT8/CK8, KRT14/CK14, KRT18/CK18 and VIM. Interacts (via N-terminus) with MARK3/C-TAK1. Interacts with DSP. Interacts with DSG1, DSG2 and DSG3. Interacts (via N-terminus) with CTNNB1. Interacts with CDH1. Interacts with the RNA polymerase III (Pol III) complex proteins POLR3A/RPC155, POLR3F/RPC39 and POLR3C/RPC82. Interacts with CTNNA3. Interacts (via N-terminus) with SCN5A/Nav1.5. Interacts with ANK3/ANKG and GJA1/CX43. (Microbial infection) Interacts (via N-terminus) with influenza A virus RNA polymerase subunit PB1 (via C-terminus); the interaction competitively inhibits the interaction between the subunits PB1 and PB2.

Subcellular location. Nucleus. Cell junction. Desmosome. Cytoplasm.

Tissue specificity. Expressed at myocyte intercalated disks in the heart (at protein level). Expressed in gingival epithelial, endothelial and fibroblast cells (at protein level). Faintly expressed in tracheal epithelial cells (at protein level). Widely expressed. Found at desmosomal plaques in simple and stratified epithelia and in non-epithelial tissues such as myocardium and lymph node follicles. In most stratified epithelia found in the desmosomes of the basal cell layer and seems to be absent from suprabasal strata. (Microbial infection) Abundantly expressed in tracheal epithelial cells following influenza A virus infection (at protein level).

Disease relevance. Arrhythmogenic right ventricular dysplasia, familial, 9 (ARVD9) [MIM:609040] 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. (Microbial infection) mRNA levels increase in response to P.gingivalis challenge while protein expression decreases, suggesting proteasomal degradation in response to P.gingivalis infection of gingival epithelial cells.

Miscellaneous. Undetected in heart. Major isoform in heart.

Similarity. Belongs to the beta-catenin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99959-1	2, B	yes
Q99959-2	1, A

RefSeq proteins (10): NP_001005242, NP_001394084, NP_001394085, NP_001394086, NP_001394087, NP_001394088, NP_001394089, NP_001394090, NP_001394091, NP_004563 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR028435	Plakophilin/d_Catenin	Family

Pfam: PF00514

UniProt features (81 total): sequence variant 31, helix 18, modified residue 16, repeat 8, region of interest 3, mutagenesis site 2, chain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3TT9	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99959-F1	64.32	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (16): 44, 46, 82, 132, 135, 151, 154, 155, 169, 172, 177, 183, 197, 251, 294, 329

Mutagenesis-validated functional residues (2):

Position	Phenotype
82	abolishes phosphorylation by mark3.
87	reduces phosphorylation of s-82 by mark3. reduces interaction with mark3.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope

MSigDB gene sets: 340 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_BUNDLE_OF_HIS_CELL_TO_PURKINJE_MYOCYTE_COMMUNICATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, LUCAS_HNF4A_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (20): desmosome assembly (GO:0002159), desmosome organization (GO:0002934), cell-cell signaling (GO:0007267), heart development (GO:0007507), positive regulation of sodium ion transport (GO:0010765), regulation of cell-substrate adhesion (GO:0010810), intermediate filament bundle assembly (GO:0045110), maintenance of animal organ identity (GO:0048496), ventricular cardiac muscle tissue morphogenesis (GO:0055010), protein localization to plasma membrane (GO:0072659), cardiac muscle cell action potential involved in contraction (GO:0086002), ventricular cardiac muscle cell action potential (GO:0086005), cell communication by electrical coupling involved in cardiac conduction (GO:0086064), bundle of His cell-Purkinje myocyte adhesion involved in cell communication (GO:0086073), regulation of heart rate by cardiac conduction (GO:0086091), cell-cell adhesion (GO:0098609), regulation of ventricular cardiac muscle cell action potential (GO:0098911), maintenance of protein localization at cell tip (GO:0099017), regulation of substrate adhesion-dependent cell spreading (GO:1900024), cell adhesion (GO:0007155)

GO Molecular Function (10): DNA binding (GO:0003677), protein kinase C binding (GO:0005080), sodium channel regulator activity (GO:0017080), intermediate filament binding (GO:0019215), transmembrane transporter binding (GO:0044325), alpha-catenin binding (GO:0045294), cadherin binding (GO:0045296), molecular adaptor activity (GO:0060090), cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication (GO:0086083), protein binding (GO:0005515)

GO Cellular Component (14): cornified envelope (GO:0001533), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), intermediate filament (GO:0005882), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), intercalated disc (GO:0014704), membrane (GO:0016020), cell junction (GO:0030054), desmosome (GO:0030057), cell tip (GO:0051286), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	3
animal organ development	2
cardiac conduction	2
protein binding	2
cell-cell junction	2
desmosome organization	1
cell-cell junction assembly	1
cell-cell junction organization	1
cell communication	1
signaling	1
circulatory system development	1
regulation of sodium ion transport	1
sodium ion transport	1
positive regulation of monoatomic ion transport	1
regulation of cell adhesion	1
cell-substrate adhesion	1
cellular component assembly	1
intermediate filament organization	1
negative regulation of cell differentiation	1
cardiac ventricle morphogenesis	1
ventricular cardiac muscle tissue development	1
cardiac muscle tissue morphogenesis	1
protein localization to membrane	1
protein localization to cell periphery	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
cardiac muscle cell action potential involved in contraction	1
cell communication by electrical coupling	1
cell communication involved in cardiac conduction	1
heterotypic cell-cell adhesion	1
cardiac muscle cell-cardiac muscle cell adhesion	1
bundle of His cell to Purkinje myocyte communication	1
regulation of heart rate	1
cell adhesion	1
regulation of cardiac muscle cell contraction	1
ventricular cardiac muscle cell action potential	1
regulation of cardiac muscle cell action potential	1
maintenance of protein location in cell	1
cell tip	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKP2	DSP	P15924	999
PKP2	DSC2	Q02487	998
PKP2	DSG2	Q14126	998
PKP2	JUP	P14923	977
PKP2	SCN5A	Q14524	976
PKP2	CTNNA3	Q9UI47	976
PKP2	GJA1	P17302	972
PKP2	DSC3	Q14574	950
PKP2	TMEM43	Q9BTV4	934
PKP2	DSG1	Q02413	878
PKP2	TGFB3	P10600	862
PKP2	RYR2	Q92736	828
PKP2	LMNA	P02545	754
PKP2	CDH2	P19022	748
PKP2	PRKCA	P17252	728

IntAct

187 interactions, top by confidence:

A	B	Type	Score
PB1	PA	psi-mi:“MI:0914”(association)	0.820
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
PB1	NP	psi-mi:“MI:0914”(association)	0.740
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MTUS2	PKP2	psi-mi:“MI:0915”(physical association)	0.670
PKP2	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
rep	POLA1	psi-mi:“MI:0914”(association)	0.670
PKP2	rep	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
PB1	PB2	psi-mi:“MI:0914”(association)	0.630
SFN	PKP2	psi-mi:“MI:0915”(physical association)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
PKP2	YWHAZ	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
PKP2	PB1	psi-mi:“MI:0915”(physical association)	0.600
PKP2	PB1	psi-mi:“MI:0403”(colocalization)	0.600

BioGRID (322): MTUS2 (Two-hybrid), NDEL1 (Two-hybrid), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PKP2 (Affinity Capture-RNA), PKP2 (Two-hybrid), PKP2 (Proximity Label-MS)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A0JMA8, A1A535, A1A5P5, B0BF33, E7F187, F1M7L9, O00443, O15013, P0C6P5, P25054, P70039, P70478, P97350, P97433, Q08AE8, Q12923, Q13835, Q14D04, Q1LXR6, Q1LYM3, Q28161, Q5EB20, Q5PQS3, Q5R5R2, Q5RAY1, Q5U245, Q5XIZ9, Q61194, Q61315, Q64512, Q6AI08, Q6ING4, Q6IRU7, Q6ZUJ8, Q7Z3E5, Q7ZY56, Q803Q4, Q8BMD7

Diamond homologs: B0BF33, F1M7L9, O35116, O35927, P97350, Q08DQ0, Q13835, Q28161, Q68FH0, Q99569, Q99959, Q9CQ73, Q9QY23, Q9UQB3, Q9Y446, B4F7F3, O00192, O60716, P30999, P98203, Q8AXM9, Q9U308, Q9C9A6, A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, O14628, O43345, O75346, O75373, O75437, O95780, P0CB33

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ZEB2	“down-regulates quantity by repression”	PKP2	“transcriptional regulation”
PKP2	down-regulates	Epithelial-mesenchymal_transition
PKP2	“up-regulates quantity by stabilization”	DSP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	42.3×	3e-09
Activation of BAD and translocation to mitochondria	7	42.0×	3e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	37.0×	6e-08
Activation of BH3-only proteins	7	27.4×	6e-07
Developmental Lineage of Mammary Gland Myoepithelial Cells	6	25.7×	6e-06
Intrinsic Pathway for Apoptosis	8	18.4×	1e-06
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	5	18.0×	2e-04
RHO GTPases activate PKNs	7	17.5×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	15.5×	3e-04
cell surface receptor protein tyrosine kinase signaling pathway	8	8.4×	2e-03
intracellular protein localization	9	5.7×	1e-02
positive regulation of cell migration	14	5.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

2357 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	232
Likely pathogenic	94
Uncertain significance	1070
Likely benign	595
Benign	52

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068825	NM_001005242.3(PKP2):c.1379-1992C>T	Pathogenic
1072271	NM_001005242.3(PKP2):c.1616_1623dup (p.Val543fs)	Pathogenic
1073811	NM_001005242.3(PKP2):c.379dup (p.Thr127fs)	Pathogenic
1074817	NM_001005242.3(PKP2):c.1217_1379-790inv	Pathogenic
1075513	NC_000012.11:g.(?32949033)(32955500_?)del	Pathogenic
1075514	NC_000012.11:g.(?33030760)(33031986_?)del	Pathogenic
1075515	NC_000012.11:g.(?32945348)(32949242_?)del	Pathogenic
1075516	NC_000012.11:g.(?33021851)(33031976_?)del	Pathogenic
1075965	NM_001005242.3(PKP2):c.582T>A (p.Tyr194Ter)	Pathogenic
1076311	NM_001005242.3(PKP2):c.1127del (p.Phe376fs)	Pathogenic
1184949	NM_001005242.3(PKP2):c.869G>A (p.Trp290Ter)	Pathogenic
1205033	NM_001005242.3(PKP2):c.1379-2A>G	Pathogenic
1297006	NM_001005242.3(PKP2):c.1368dup (p.Gln457fs)	Pathogenic
1321424	NM_001005242.3(PKP2):c.2044C>T (p.Gln682Ter)	Pathogenic
1329270	NM_001005242.3(PKP2):c.1379-1_1556+1del	Pathogenic
1335099	NM_001005242.3(PKP2):c.1A>C (p.Met1Leu)	Pathogenic
1344540	NM_001005242.3(PKP2):c.336+1G>T	Pathogenic
1354302	NM_001005242.3(PKP2):c.1738G>T (p.Glu580Ter)	Pathogenic
1358209	NM_001005242.3(PKP2):c.329dup (p.Met110fs)	Pathogenic
1369432	NM_001005242.3(PKP2):c.2408_2411del (p.Leu803fs)	Pathogenic
1372358	NM_001005242.3(PKP2):c.472_473del (p.Arg158fs)	Pathogenic
1380244	NM_001005242.3(PKP2):c.759_769del (p.Asn254fs)	Pathogenic
1394074	NM_001005242.3(PKP2):c.464dup (p.Ser155fs)	Pathogenic
1400125	NM_001005242.3(PKP2):c.253G>T (p.Glu85Ter)	Pathogenic
1412205	NM_001005242.3(PKP2):c.1750C>T (p.Gln584Ter)	Pathogenic
1443926	NM_001005242.3(PKP2):c.1264_1265del (p.Leu422fs)	Pathogenic
1452110	NM_001005242.3(PKP2):c.1842dup (p.Tyr615fs)	Pathogenic
1453476	NC_000012.11:g.(?33030760)(33049665_?)del	Pathogenic
1454572	NM_001005242.3(PKP2):c.296_300dup (p.Arg101fs)	Pathogenic
1455995	NC_000012.11:g.(?33003680)(33003927_?)del	Pathogenic

SpliceAI

1812 predictions. Top by Δscore:

Variant	Effect	Δscore
12:32792643:CCTT:C	donor_gain	1.0000
12:32792727:CATAG:C	acceptor_gain	1.0000
12:32792729:TAG:T	acceptor_gain	1.0000
12:32792732:C:CC	acceptor_gain	1.0000
12:32796107:A:AC	donor_gain	1.0000
12:32796108:C:CC	donor_gain	1.0000
12:32796108:CG:C	donor_gain	1.0000
12:32796111:ATCG:A	donor_gain	1.0000
12:32796299:C:CC	acceptor_gain	1.0000
12:32802399:TCA:T	donor_loss	1.0000
12:32802400:C:CG	donor_loss	1.0000
12:32802401:A:AC	donor_gain	1.0000
12:32802401:A:AT	donor_loss	1.0000
12:32802402:C:CC	donor_gain	1.0000
12:32821347:AATAC:A	donor_loss	1.0000
12:32821348:ATACT:A	donor_loss	1.0000
12:32821350:A:AC	donor_gain	1.0000
12:32821350:ACT:A	donor_loss	1.0000
12:32821351:C:CC	donor_gain	1.0000
12:32821351:CTC:C	donor_loss	1.0000
12:32821351:CTCA:C	donor_gain	1.0000
12:32821352:TCAC:T	donor_loss	1.0000
12:32821353:CACT:C	donor_loss	1.0000
12:32821354:A:AC	donor_gain	1.0000
12:32821354:ACTG:A	donor_loss	1.0000
12:32821355:C:CT	donor_gain	1.0000
12:32821355:CT:C	donor_gain	1.0000
12:32821355:CTG:C	donor_gain	1.0000
12:32821355:CTGG:C	donor_gain	1.0000
12:32821355:CTGGT:C	donor_gain	1.0000

AlphaMissense

5491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:32792470:A:G	F867S	0.999
12:32821375:A:G	L709P	0.999
12:32821377:G:C	N708K	0.999
12:32821377:G:T	N708K	0.999
12:32821384:A:G	L706P	0.999
12:32822597:A:G	L614P	0.999
12:32824132:T:A	R573S	0.999
12:32824132:T:G	R573S	0.999
12:32824153:A:C	S566R	0.999
12:32824153:A:T	S566R	0.999
12:32824155:T:G	S566R	0.999
12:32841028:C:G	R563T	0.999
12:32841031:A:G	L562P	0.999
12:32796212:A:G	C796R	0.998
12:32802435:A:G	L756P	0.998
12:32802447:A:G	L752P	0.998
12:32821379:T:C	N708D	0.998
12:32822606:A:G	L611P	0.998
12:32824094:A:G	L586P	0.998
12:32824162:T:A	R563S	0.998
12:32824162:T:G	R563S	0.998
12:32841028:C:A	R563I	0.998
12:32792690:A:G	L844P	0.997
12:32792702:G:T	A840D	0.997
12:32796160:A:G	L813P	0.997
12:32821390:C:T	G704E	0.997
12:32821391:C:G	G704R	0.997
12:32821391:C:T	G704R	0.997
12:32822599:G:C	N613K	0.997
12:32822599:G:T	N613K	0.997

dbSNP variants (sampled 300 via entrez): RS1000009571 (12:32846415 G>T), RS1000038586 (12:32870180 T>C), RS1000110100 (12:32826230 C>A,T), RS1000152941 (12:32824620 T>G), RS1000158281 (12:32807935 G>C), RS1000180273 (12:32849753 T>C), RS1000192501 (12:32893769 A>G), RS1000199768 (12:32894015 G>C,T), RS1000208487 (12:32887382 A>G), RS1000256647 (12:32863285 G>A), RS1000264588 (12:32819370 T>C), RS1000273239 (12:32894646 C>A), RS1000303375 (12:32856320 CTA>C), RS1000313011 (12:32799129 G>A,C,T), RS1000337282 (12:32812110 G>A)

Disease associations

OMIM: gene MIM:602861 | disease phenotypes: MIM:609040, MIM:107970, MIM:115200, MIM:300376, MIM:302045, MIM:310200, MIM:601144, MIM:192600, MIM:603829, MIM:192500, MIM:105210, MIM:613426, MIM:604169, MIM:115080

GenCC curated gene-disease

Disease	Classification	Inheritance
arrhythmogenic right ventricular dysplasia 9	Definitive	Autosomal dominant
left ventricular noncompaction	Supportive	Autosomal dominant
Brugada syndrome	Limited	Autosomal dominant
Brugada syndrome 1	Disputed Evidence	Autosomal dominant
catecholaminergic polymorphic ventricular tachycardia	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (4)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
catecholaminergic polymorphic ventricular tachycardia	Disputed	AD
dilated cardiomyopathy	Disputed	AD
arrhythmogenic right ventricular cardiomyopathy	Definitive	AD
Brugada syndrome 1	Disputed	AD

Mondo (26): arrhythmogenic right ventricular dysplasia 9 (MONDO:0012180), cardiomyopathy (MONDO:0004994), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), familial isolated arrhythmogenic right ventricular dysplasia (MONDO:0016342), long QT syndrome (MONDO:0002442), ventricular tachycardia (MONDO:0005477), dilated cardiomyopathy 1A (MONDO:0007269), dilated cardiomyopathy (MONDO:0005021), Becker muscular dystrophy (MONDO:0010311), dilated cardiomyopathy 3B (MONDO:0010542), Duchenne muscular dystrophy (MONDO:0010679), Brugada syndrome (MONDO:0015263), hypertrophic cardiomyopathy (MONDO:0005045), familial hypertrophic cardiomyopathy (MONDO:0024573), ventricular fibrillation, paroxysmal familial, type 1 (MONDO:0011376)

Orphanet (20): Rare cardiomyopathy (Orphanet:167848), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Inherited isolated arrhythmogenic cardiomyopathy (Orphanet:217656), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Brugada syndrome (Orphanet:130), Familial isolated dilated cardiomyopathy (Orphanet:154), Dilated cardiomyopathy (Orphanet:217604), Becker muscular dystrophy (Orphanet:98895), Duchenne muscular dystrophy (Orphanet:98896), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Idiopathic ventricular fibrillation (Orphanet:228140), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), ATTRV30M amyloidosis (Orphanet:85447)

HPO phenotypes

24 total (26 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001279	Syncope
HP:0001645	Sudden cardiac death
HP:0001649	Tachycardia
HP:0001663	Ventricular fibrillation
HP:0001695	Cardiac arrest
HP:0001962	Palpitations
HP:0002094	Dyspnea
HP:0004308	Ventricular arrhythmia
HP:0004751	Paroxysmal ventricular tachycardia
HP:0004755	Supraventricular tachycardia
HP:0004756	Ventricular tachycardia
HP:0006677	Prolonged QRS complex
HP:0006682	Premature ventricular contraction
HP:0006698	Dilatation of the ventricular cavity
HP:0011462	Young adult onset
HP:0011663	Right ventricular cardiomyopathy
HP:0011704	Sick sinus syndrome
HP:0011705	First degree atrioventricular block
HP:0011712	Complete right bundle branch block
HP:0011715	Trifascicular block
HP:0012251	ST segment elevation
HP:0034304	Epsilon wave
HP:0034364	Fibrofatty replacement of right ventricular myocardium
HP:0001644	Dilated cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001762_250	Obesity-related traits	9.000000e-06
GCST001762_759	Obesity-related traits	3.000000e-06
GCST001762_784	Obesity-related traits	3.000000e-06
GCST003984_3	Parkinson’s disease	4.000000e-21
GCST004104_3	Body mass index (change over time) in lung cancer	4.000000e-06
GCST004136_32	Methadone dose in opioid dependence	7.000000e-06
GCST004301_7	Prevalent atrial fibrillation	4.000000e-08
GCST006061_218	Atrial fibrillation	5.000000e-16
GCST006061_219	Atrial fibrillation	3.000000e-16
GCST006414_10	Atrial fibrillation	3.000000e-14
GCST006585_2679	Blood protein levels	2.000000e-06
GCST008442_3	Periodontal disease related phenotype (PCT5)	1.000000e-08
GCST010991_14	Parkinson’s disease	6.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement
EFO:0005937	longitudinal BMI measurement
EFO:0007907	methadone dose measurement
EFO:0007780	periodontal measurement

MeSH disease descriptors (15)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D020388	Muscular Dystrophy, Duchenne	C05.651.534.500.300; C10.668.491.175.500.300; C16.320.322.562; C16.320.577.300
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014693	Ventricular Fibrillation	C14.280.067.922; C23.550.073.922
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 (supp.)
C570377	Benign Pseudohypertrophic Muscular Dystrophy (supp.)
C563538	Cardiomyopathy, Dilated, 1s (supp.)
C580047	Dmd-Associated Dilated Cardiomyopathy (supp.)
C567851	Ventricular Fibrillation, Paroxysmal Familial, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	3
Acetaminophen	decreases expression	3
Estradiol	affects expression, affects binding, decreases expression, affects cotreatment	3
mercuric bromide	increases expression, affects cotreatment	2
Lipopolysaccharides	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	decreases expression	2
Smoke	decreases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
potassium perchlorate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
doxifluridine	increases response to substance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
1-UFT protocol	increases response to substance	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1

Cellosaurus cell lines

23 cell lines: 20 induced pluripotent stem cell, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0LT	EURACi006-A	Induced pluripotent stem cell	Male
CVCL_A0LU	EURACi006-A-1	Induced pluripotent stem cell	Male
CVCL_A0LV	EURACi007-A	Induced pluripotent stem cell	Female
CVCL_A0LW	EURACi008-A	Induced pluripotent stem cell	Female
CVCL_A5FW	SCVIi003-A	Induced pluripotent stem cell	Male
CVCL_A5FX	SCVIi004-A	Induced pluripotent stem cell	Female
CVCL_A5FY	SCVIi005-A	Induced pluripotent stem cell	Male
CVCL_A5QH	JMUi001-A-2	Induced pluripotent stem cell	Male
CVCL_A6XG	USFi004-A	Induced pluripotent stem cell	Female
CVCL_C9LG	INEUi002-A-1	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

358 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
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