VCL

Summary

VCL (vinculin, HGNC:12665) is a protein-coding gene on chromosome 10q22.2, encoding Vinculin (P18206). Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. It is a selective cancer dependency (DepMap: 22.0% of cell lines).

Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Defects in VCL are the cause of cardiomyopathy dilated type 1W. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.

Source: NCBI Gene 7414 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy 1W (Strong, ClinGen) — +4 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 1,726 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 22.0% of screened cell lines
• MANE Select transcript: NM_014000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12665
Approved symbol	VCL
Name	vinculin
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	VINC
Ensembl gene	ENSG00000035403
Ensembl biotype	protein_coding
OMIM	193065
Entrez	7414

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000211998, ENST00000372755, ENST00000461383, ENST00000472585, ENST00000478896, ENST00000623461, ENST00000624354, ENST00000881823, ENST00000881824, ENST00000881825, ENST00000881826, ENST00000881827, ENST00000881828, ENST00000927509, ENST00000927510, ENST00000927511, ENST00000927512, ENST00000965704, ENST00000965705

RefSeq mRNA: 2 — MANE Select: NM_014000 NM_003373, NM_014000

CCDS: CCDS7340, CCDS7341

Canonical transcript exons

ENST00000211998 — 22 exons

Exon	Start	End
ENSE00000000338	73998116	73998375
ENSE00000709651	74111909	74112112
ENSE00000709670	74114184	74114387
ENSE00000834577	74108971	74109156
ENSE00000986356	74083366	74083513
ENSE00000986357	74089196	74089349
ENSE00000986358	74090023	74090198
ENSE00000986360	74095656	74095855
ENSE00000986361	74097204	74097332
ENSE00000986362	74100948	74101097
ENSE00000986364	74105051	74105353
ENSE00000986366	74114795	74114899
ENSE00001024245	74070975	74071083
ENSE00001024248	74082454	74082544
ENSE00001024249	74072730	74072852
ENSE00001024262	74094271	74094461
ENSE00001024263	74074743	74074903
ENSE00001765583	74118023	74120169
ENSE00002495268	74070670	74070820
ENSE00003463820	74103820	74103928
ENSE00003488226	74107230	74107354
ENSE00003619768	74043083	74043153

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 142.9782 / max 1400.9435, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105571	142.9782	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.66	gold quality
blood vessel layer	UBERON:0004797	99.63	gold quality
urethra	UBERON:0000057	99.53	gold quality
vein	UBERON:0001638	99.51	gold quality
vena cava	UBERON:0004087	99.09	gold quality
smooth muscle tissue	UBERON:0001135	98.96	gold quality
right coronary artery	UBERON:0001625	98.89	gold quality
popliteal artery	UBERON:0002250	98.78	gold quality
tibial artery	UBERON:0007610	98.78	gold quality
artery	UBERON:0001637	98.69	gold quality
aorta	UBERON:0000947	98.66	gold quality
nipple	UBERON:0002030	98.65	gold quality
seminal vesicle	UBERON:0000998	98.64	gold quality
descending thoracic aorta	UBERON:0002345	98.61	gold quality
left ventricle myocardium	UBERON:0006566	98.53	gold quality
myometrium	UBERON:0001296	98.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.52	gold quality
cauda epididymis	UBERON:0004360	98.51	gold quality
lower esophagus	UBERON:0013473	98.50	gold quality
thoracic aorta	UBERON:0001515	98.49	gold quality
ascending aorta	UBERON:0001496	98.46	gold quality
adult organism	UBERON:0007023	98.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.35	gold quality
pylorus	UBERON:0001166	98.33	gold quality
dorsal root ganglion	UBERON:0000044	98.22	gold quality
mammary duct	UBERON:0001765	98.20	gold quality
epithelium of mammary gland	UBERON:0003244	98.18	gold quality
coronary artery	UBERON:0001621	98.13	gold quality
stromal cell of endometrium	CL:0002255	98.11	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	171.61
E-HCAD-10	yes	35.56
E-CURD-112	yes	33.83
E-CURD-122	yes	23.55
E-MTAB-9221	yes	22.24
E-HCAD-6	yes	18.52
E-MTAB-9067	yes	13.13
E-GEOD-84465	yes	6.53
E-HCAD-11	yes	6.46
E-GEOD-124858	no	871.92
E-MTAB-7008	no	860.92
E-MTAB-8205	no	430.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EZH2

miRNA regulators (miRDB)

165 targeting VCL, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Here, we report on a transient interaction between the lipid-dependent protein kinase Calpha and vinculin, an early component of these sites, during spreading of HeLa cells on collagen (PMID:11741957)
• crystal structures of human vinculin in its inactive and talin-activated states (PMID:14702644)
• Findings support a model in which talin binds to and activates multiple vinculin molecules to provoke rapid reorganization of the actin cytoskeleton. (PMID:15070891)
• vinculin is tyrosine phosphorylated in platelets spread on fibrinogen, and the phosphorylation is Src kinases dependent (PMID:15229287)
• immunohistochemistry of vinculin in alpha- and gamma-sarcoglycanopathy (PMID:15547664)
• two head-tail interfaces cooperate to suppress activation of vinculin by talin (PMID:15728584)
• Beyond providing direct evidence that vinculin is activated at focal adhesions, this study shows that the specific functional conformation correlates with regional cellular dynamics. (PMID:15883197)
• A model is suggested where vinculin’s Vh1 domain acts as a molecular switch that undergoes distinct structural changes provoked by talin and alpha-actinin binding in focal adhesions versus adherens junctions, respectively. (PMID:15988023)
• Same fundamental metavinculin mutation can yield either hypertrophic or dilated cardiomyopathic phenotype, underscoring a critical role for modifier genes and/or environmental stressors in cardiac remodeling. (PMID:16236538)
• vinculin binding to talin depends on stability of the helical bundles that make up the talin rod (PMID:16407302)
• vinculin conformation, as modulated by the strength of HTI, directly regulates the formation and lifetime of talin-vinculin complexes in cells (PMID:16608855)
• a vinculin missense mutation confers susceptibility to hypertrophic cardiomyopathy (PMID:16712796)
• Vinculin is activated by virulence factor of Shigella flexneri. (PMID:16826238)
• cardiac hypertrophy may be associated with different expression of the marker vinculin/metavinculin depending on the underlying pathophysiology (PMID:16949038)
• Invasin IpaA subverts vinculin’s functions. Shigella flexneri utilizes a remarkable level of molecular mimicry of the talin-vinculin interaction to activate vinculin. (PMID:17088427)
• Results decribe a mechanism in which signals from the T cell receptor produce WAVE2-ARP2/3-mediated de novo actin polymerization, leading to integrin clustering and high-affinity binding through the recruitment of vinculin and talin. (PMID:17591693)
• vinculin plays a role in growth regulation of neuroendocrine tumors and in expression of CLD4 (PMID:17709988)
• analysis of vinculin binding in its closed conformation by a helix addition mechanism (PMID:17932491)
• alpha-synemin, but not beta-synemin, interacts with both vinculin and metavinculin (PMID:18028034)
• The expression of vinculin constructs with unmasked binding sites in the head and tail regions induces dramatic focal adhesion growth, which is mediated by their direct interaction with talin. (PMID:18056416)
• A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three organs and may represent general cancer-related splicing events. (PMID:18353764)
• The structural and biochemical properties of the last 21 residues of the vinculin tail domain were investigated. (PMID:18554503)
• Vinculin has a similar staining pattern in liver as CRBP-1 but additionally stains SMCs, and (myo)fibroblasts. (PMID:19052772)
• the vinculin-talin-integrin system have a role in the transduction of mechanical force to the extracellular matrix (PMID:19148538)
• Experiments on a nonphosphorylatable vinculin mutant construct at phosphorylation site tyr1065 confirmed the direct interplay between phosphorylation and exchange dynamics of adhesion proteins during adhesion site maturation. (PMID:19422016)
• Focal adhesion kinase expression reduced vinculin localization to focal adhesions by 35% independently of changes in integrin binding and localization of talin and paxillin. (PMID:19883375)
• This review discusses the general function of vinculin/metavinulin as well as talin 1 and talin 2, with emphasis on what is understood about their role in the cardiac myocyte and in whole heart. (PMID:19952892)
• an interaction between beta-catenin and vinculin is crucial for stabilizing E-cadherin at the cell surface (PMID:20086044)
• A helix replacement mechanism directs metavinculin’s unique functions. (PMID:20502710)
• The data identify the kidney as a new organ site for ALK-associated carcinomas and VCL as a novel ALK fusion partner. (PMID:21076462)
• VCL is expressed differently in benign prostatic hyperplasia and prostate cancer, which may serve as an indicator for the differential diagnosis of benign and malignant prostate diseases. (PMID:21171262)
• When myosin II contractility was inhibited, the k(off) values for all three proteins changed rapidly, in a highly protein-specific manner: dissociation of vinculin from FAs was facilitated, whereas dissociation of paxillin and zyxin was attenuated. (PMID:21486952)
• IpaA-directed mimicry of talin in activating vinculin occurs through three high affinity VBSs that are essential for Shigella pathogenesis. (PMID:21525010)
• Talin-1 and vinculin negatively affect tyrosine phosphorylation of paxillin, a novel positive regulator of HIV-1 infection, and impose an early block to infection by distinct retroviruses. (PMID:21763488)
• sca4 activates vinculin and interacts with the actin cytoskeleton; vinculin has roles in Rickettsia pathogenesis (PMID:21841197)
• alpha-catenin employs a novel mechanism to activate vinculin and may explain how vinculin is differentially recruited and/or activated in cell-cell and cell-matrix adhesions. (PMID:22235119)
• Data show that SGK1 regulates cell migration via vinculin dephosphorylation, a mechanism that is controlled by membrane androgen receptor function. (PMID:22309306)
• Results implicate Vinculin-dependent VE-cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis. (PMID:22391038)
• binding studies suggest that vinculin must be in an activated state to bind to alpha-catenin and that this interaction is stabilized by the formation of a ternary alpha-catenin-vinculin-F-actin complex, which can be formed via the F-actin binding domain (PMID:22493458)
• The metavinculin promoted severing of actin filaments, most efficiently at substoichiometric concentrations. (PMID:22613835)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	vcla	ENSDARG00000044968
danio_rerio	vclb	ENSDARG00000098695
mus_musculus	Vcl	ENSMUSG00000021823
rattus_norvegicus	Vcl	ENSRNOG00000010765
drosophila_melanogaster	Vinc	FBGN0004397
caenorhabditis_elegans		WBGENE00000942

Paralogs (4): CTNNA1 (ENSG00000044115), CTNNA2 (ENSG00000066032), CTNNAL1 (ENSG00000119326), CTNNA3 (ENSG00000183230)

Protein

Protein identifiers

Vinculin — P18206 (reviewed: P18206)

Alternative names: Metavinculin

All UniProt accessions (4): A0A096LPE1, B4DTM7, P18206, V9HWK2

UniProt curated annotations — full annotation on UniProt →

Function. Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.

Subunit / interactions. Exhibits self-association properties. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL. Interacts with APBB1IP and NRAP. Interacts with TLN1. Interacts with CTNNB1 and this interaction is necessary for its localization to the cell-cell junctions and for its function in regulating cell surface expression of E-cadherin. Interacts with SYNM. Interacts with SORBS1. Interacts with CTNNA1. Binds to ACTN4; this interaction triggers conformational changes. Interacts with FLII. Interacts with FER1L6. (Microbial infection) Interacts via its globular head domain with the central portion of S.flexneri IcsA (also called VirG).

Subcellular location. Cell membrane. Cell junction. Adherens junction. Focal adhesion. Cytoplasm. Cytoskeleton. Sarcolemma. Cell projection. Podosome. Perinuclear region.

Tissue specificity. Metavinculin is muscle-specific.

Post-translational modifications. Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1133 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques. Acetylated; mainly by myristic acid but also by a small amount of palmitic acid.

Disease relevance. Cardiomyopathy, dilated, 1W (CMD1W) [MIM:611407] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, familial hypertrophic, 15 (CMH15) [MIM:613255] A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Exists in at least two conformations. When in the closed, ‘inactive’ conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an ‘active’ conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion. The N-terminal globular head (Vh) comprises of subdomains D1-D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. In isoform 2 (metavinculin) a 68 residue insertion in the tail domain promotes actin severing instead of bundling. An intramolecular interaction between Vh and Vt masks the F-actin-binding domain located in Vt. The binding of talin and alpha-actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin-binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly.

Similarity. Belongs to the vinculin/alpha-catenin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P18206-1	2, Metavinculin	yes
P18206-2	1, Vinculin
P18206-3	3

RefSeq proteins (2): NP_003364, NP_054706* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000633	Vinculin_CS	Conserved_site
IPR006077	Vinculin/catenin	Family
IPR017997	Vinculin	Family
IPR036723	Alpha-catenin/vinculin-like_sf	Homologous_superfamily

Pfam: PF01044

UniProt features (105 total): helix 43, modified residue 21, region of interest 9, strand 9, turn 8, sequence variant 6, splice variant 4, repeat 3, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4LN2	X-RAY DIFFRACTION	1
4LNP	X-RAY DIFFRACTION	1.41
3RF3	X-RAY DIFFRACTION	1.61
1YDI	X-RAY DIFFRACTION	1.8
3S90	X-RAY DIFFRACTION	1.97
3TJ5	X-RAY DIFFRACTION	1.99
3MYI	X-RAY DIFFRACTION	2.2
4DJ9	X-RAY DIFFRACTION	2.25
1RKE	X-RAY DIFFRACTION	2.35
1SYQ	X-RAY DIFFRACTION	2.42
5L0I	X-RAY DIFFRACTION	2.45
3VF0	X-RAY DIFFRACTION	2.54
9QWO	X-RAY DIFFRACTION	2.54
4EHP	X-RAY DIFFRACTION	2.66
1RKC	X-RAY DIFFRACTION	2.7
2GWW	X-RAY DIFFRACTION	2.72
3H2U	X-RAY DIFFRACTION	2.75
5L0D	X-RAY DIFFRACTION	2.75
3TJ6	X-RAY DIFFRACTION	2.76
5L0F	X-RAY DIFFRACTION	2.76
1TR2	X-RAY DIFFRACTION	2.9
3H2V	X-RAY DIFFRACTION	2.9
5L0H	X-RAY DIFFRACTION	2.9
6UPW	ELECTRON MICROSCOPY	2.9
6FUY	X-RAY DIFFRACTION	3
5L0C	X-RAY DIFFRACTION	3.1
2IBF	X-RAY DIFFRACTION	3.2
4PR9	X-RAY DIFFRACTION	3.2
5L0G	X-RAY DIFFRACTION	3.4
2HSQ	X-RAY DIFFRACTION	3.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18206-F1	86.69	0.63

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 (21): 97, 173, 260, 272, 275, 288, 290, 346, 434, 496, 537, 574, 579, 600, 604, 672, 721, 795, 809, 822 …

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-445355	Smooth Muscle Contraction
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-6798695	Neutrophil degranulation
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9764561	Regulation of CDH1 Function
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-9958825	Activation of STAT3 by cadherin engagement

MSigDB gene sets: 603 (showing top): BIOCARTA_RHO_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, AP1_01, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEURON_PROJECTION_EXTENSION, LU_IL4_SIGNALING, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, CHUNG_BLISTER_CYTOTOXICITY_DN

GO Biological Process (16): morphogenesis of an epithelium (GO:0002009), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), lamellipodium assembly (GO:0030032), negative regulation of cell migration (GO:0030336), adherens junction assembly (GO:0034333), protein localization to cell surface (GO:0034394), maintenance of blood-brain barrier (GO:0035633), apical junction assembly (GO:0043297), axon extension (GO:0048675), regulation of focal adhesion assembly (GO:0051893), platelet aggregation (GO:0070527), epithelial cell-cell adhesion (GO:0090136), regulation of establishment of endothelial barrier (GO:1903140), regulation of protein localization to adherens junction (GO:1904702), regulation of cell migration (GO:0030334)

GO Molecular Function (10): dystroglycan binding (GO:0002162), actin binding (GO:0003779), structural molecule activity (GO:0005198), beta-catenin binding (GO:0008013), ubiquitin protein ligase binding (GO:0031625), alpha-catenin binding (GO:0045294), cadherin binding (GO:0045296), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), actin filament binding (GO:0051015)

GO Cellular Component (33): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), brush border (GO:0005903), cell-cell junction (GO:0005911), adherens junction (GO:0005912), zonula adherens (GO:0005915), fascia adherens (GO:0005916), focal adhesion (GO:0005925), cell-substrate junction (GO:0030055), protein-containing complex (GO:0032991), secretory granule lumen (GO:0034774), specific granule lumen (GO:0035580), sarcolemma (GO:0042383), costamere (GO:0043034), cell-cell contact zone (GO:0044291), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), podosome ring (GO:0061826), extracellular exosome (GO:0070062), outer dense plaque of desmosome (GO:0090636), inner dense plaque of desmosome (GO:0090637), extracellular vesicle (GO:1903561), ficolin-1-rich granule lumen (GO:1904813), terminal web (GO:1990357), podosome (GO:0002102), actin cytoskeleton (GO:0015629), membrane (GO:0016020), myofibril (GO:0030016), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Oncogenic MAPK signaling	5
Response of endothelial cells to shear stress	2
Response to elevated platelet cytosolic Ca2+	1
Muscle contraction	1
RAF/MAP kinase cascade	1
Innate Immune System	1
Signaling by RAS mutants	1
Signaling by ALK in cancer	1
Regulation of CDH1 Expression and Function	1
Adherens junctions interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	3
cell-cell junction	3
cell migration	2
cell-cell junction assembly	2
molecular_function	2
binding	2
cytoplasm	2
anchoring junction	2
tissue morphogenesis	1
epithelium development	1
cellular process	1
cell-substrate adhesion	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
regulation of cell migration	1
negative regulation of cell motility	1
adherens junction organization	1
intracellular protein localization	1
tissue homeostasis	1
axonogenesis	1
neuron projection extension	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
platelet activation	1
homotypic cell-cell adhesion	1
cell-cell adhesion	1
establishment of endothelial barrier	1
regulation of endothelial cell development	1
protein localization to adherens junction	1
regulation of protein localization to cell-cell junction	1
regulation of cell motility	1
cytoskeletal protein binding	1
ubiquitin-like protein ligase binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

4016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCL	PXN	P49023	999
VCL	ZYX	Q15942	999
VCL	TLN1	Q9Y490	999
VCL	TLN2	Q9Y4G6	999
VCL	VASP	P50552	998
VCL	PTK2	Q05397	998
VCL	BCAR1	P56945	997
VCL	SRC	P12931	995
VCL	FLNA	P21333	995
VCL	FLNB	O75369	994
VCL	ILK	P57043	994
VCL	FLNC	Q14315	994
VCL	SORBS3	O60504	993
VCL	CTNNB1	P35222	993
VCL	CDH1	P12830	991

IntAct

116 interactions, top by confidence:

A	B	Type	Score
VCL	ipaA	psi-mi:“MI:0407”(direct interaction)	0.760
ipaA	VCL	psi-mi:“MI:0407”(direct interaction)	0.760
ipaA	VCL	psi-mi:“MI:0915”(physical association)	0.760
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
ipaA	VCL	psi-mi:“MI:0407”(direct interaction)	0.720
VCL	ipaA	psi-mi:“MI:0407”(direct interaction)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
VCL		psi-mi:“MI:0407”(direct interaction)	0.650
	VCL	psi-mi:“MI:0915”(physical association)	0.650
	VCL	psi-mi:“MI:0407”(direct interaction)	0.650
Sorbs1	VCL	psi-mi:“MI:0915”(physical association)	0.590
VCL	Sorbs1	psi-mi:“MI:0915”(physical association)	0.590
TEKT1	VCL	psi-mi:“MI:0915”(physical association)	0.560
VCL	TEKT1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (363): VCL (Two-hybrid), TEKT1 (Two-hybrid), ABI2 (Two-hybrid), C19orf57 (Two-hybrid), VCL (Two-hybrid), VCL (Affinity Capture-RNA), FERMT2 (Co-fractionation), PICALM (Co-fractionation), PXN (Co-fractionation), VCL (Affinity Capture-MS), VCL (Reconstituted Complex), VCL (Proximity Label-MS), VCL (Proximity Label-MS), VCL (Two-hybrid), LPXN (Two-hybrid)

ESM2 similar proteins: A0A3B6UES5, A0A3G2LGI8, D3ZHV2, G8JYB2, O46037, O60437, P0CE94, P0CE95, P11533, P12003, P18206, P19826, P26039, P26231, P26234, P30427, P33338, P35220, P35221, P54939, P85972, P90947, Q02328, Q03001, Q04615, Q15149, Q17162, Q3MHM6, Q54K81, Q54MH2, Q59I72, Q64727, Q6ZWR6, Q71LX4, Q8MSU4, Q91ZU6, Q95XZ0, Q9ERE8, Q9H1K6, Q9MBF8

Diamond homologs: A0A3B6UES5, O46037, P12003, P18206, P26234, P85972, Q04615, Q64727, P19826, Q17162, Q54MH2, A4IGI7, B7ZC77, P26231, P26232, P30997, P35220, P35221, Q3MHM6, Q59I72, Q5R416, Q61301, Q65CL1, Q6GLP0, Q9PVF8, Q9UI47

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	VCL	phosphorylation
SRC	“down-regulates activity”	VCL	phosphorylation
PRKCA	unknown	VCL	phosphorylation
PTPRG	“down-regulates activity”	VCL	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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
Degradation of CDH1	6	16.6×	5e-04
Activation of STAT3 by cadherin engagement	6	13.8×	1e-03
Transcriptional and post-translational regulation of MITF-M expression and activity	5	12.6×	3e-03
Programmed Cell Death	6	12.4×	1e-03
Signaling by BRAF and RAF1 fusions	5	12.0×	3e-03
Apoptosis	5	11.8×	3e-03
SARS-CoV-1 Infection	5	10.1×	6e-03
Transcriptional regulation of granulopoiesis	5	8.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	15.8×	7e-03
positive regulation of non-canonical NF-kappaB signal transduction	5	13.9×	7e-03
transforming growth factor beta receptor signaling pathway	6	10.4×	7e-03
cell-cell adhesion	7	7.7×	7e-03
cell migration	9	6.0×	7e-03
positive regulation of gene expression	13	5.5×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1726 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	944
Likely benign	590
Benign	55

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1184903	NM_014000.3(VCL):c.176_177del (p.Lys59fs)	Pathogenic
166546	NM_014000.3(VCL):c.1544-2A>G	Likely pathogenic
1678145	NM_014000.3(VCL):c.2560-2A>T	Likely pathogenic
217497	NM_014000.3(VCL):c.1531G>T (p.Asp511Tyr)	Likely pathogenic
3895158	NM_014000.2:c.2298_(3258+1_3259-1)dup	Likely pathogenic

SpliceAI

4192 predictions. Top by Δscore:

Variant	Effect	Δscore
10:74043078:T:A	acceptor_gain	1.0000
10:74043078:TGTA:T	acceptor_loss	1.0000
10:74043080:TA:T	acceptor_loss	1.0000
10:74043081:A:AG	acceptor_gain	1.0000
10:74043081:A:T	acceptor_loss	1.0000
10:74043081:AG:A	acceptor_gain	1.0000
10:74043081:AGGTT:A	acceptor_gain	1.0000
10:74043082:G:GA	acceptor_gain	1.0000
10:74043082:GG:G	acceptor_gain	1.0000
10:74043082:GGT:G	acceptor_gain	1.0000
10:74043082:GGTT:G	acceptor_gain	1.0000
10:74043082:GGTTG:G	acceptor_gain	1.0000
10:74043149:ATTAA:A	donor_gain	1.0000
10:74043150:TTAA:T	donor_gain	1.0000
10:74043151:TAA:T	donor_gain	1.0000
10:74043152:AA:A	donor_gain	1.0000
10:74043153:AGT:A	donor_loss	1.0000
10:74043154:G:C	donor_loss	1.0000
10:74043154:G:GG	donor_gain	1.0000
10:74043158:G:GG	donor_gain	1.0000
10:74067989:T:G	acceptor_gain	1.0000
10:74070666:ATAG:A	acceptor_gain	1.0000
10:74070667:TAGG:T	acceptor_loss	1.0000
10:74070668:A:AG	acceptor_gain	1.0000
10:74070668:AG:A	acceptor_gain	1.0000
10:74070669:G:GG	acceptor_gain	1.0000
10:74070669:GG:G	acceptor_gain	1.0000
10:74070816:CTGAG:C	donor_loss	1.0000
10:74070817:TGAGG:T	donor_loss	1.0000
10:74070818:GAGGT:G	donor_loss	1.0000

AlphaMissense

7398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73998217:T:C	F4L	1.000
10:73998219:T:A	F4L	1.000
10:73998219:T:G	F4L	1.000
10:73998233:T:A	I9N	1.000
10:73998245:T:C	L13P	1.000
10:73998275:T:C	L23P	1.000
10:73998368:T:C	L54P	1.000
10:74043086:G:A	G58R	1.000
10:74043086:G:C	G58R	1.000
10:74070693:T:C	L88P	1.000
10:74070701:G:C	A91P	1.000
10:74070714:T:C	L95P	1.000
10:74070744:G:C	R105P	1.000
10:74070753:T:C	L108P	1.000
10:74070761:G:A	G111R	1.000
10:74070761:G:C	G111R	1.000
10:74070761:G:T	G111W	1.000
10:74070762:G:A	G111E	1.000
10:74070777:T:A	L116H	1.000
10:74070777:T:C	L116P	1.000
10:74070795:T:C	L122P	1.000
10:74070798:T:A	L123H	1.000
10:74070798:T:C	L123P	1.000
10:74070801:T:C	L124P	1.000
10:74070809:G:C	D127H	1.000
10:74070810:A:C	D127A	1.000
10:74070810:A:T	D127V	1.000
10:74070815:G:C	A129P	1.000
10:74070998:C:G	C138W	1.000
10:74071018:T:C	L145P	1.000

dbSNP variants (sampled 300 via entrez): RS1000027692 (10:74003716 C>T), RS1000044466 (10:74033678 G>A), RS1000045117 (10:74063631 A>G), RS1000104347 (10:74016602 T>A), RS1000111573 (10:74051957 C>A,G,T), RS1000113400 (10:74011101 G>A), RS1000120226 (10:74111604 A>G), RS1000140728 (10:74100841 A>G), RS1000165003 (10:74103171 T>G), RS1000186828 (10:74036935 G>A), RS1000202729 (10:74109769 T>C), RS1000236913 (10:74019414 C>G), RS1000312250 (10:74073866 T>A), RS1000340898 (10:74012999 T>A), RS1000407612 (10:73998561 G>A,C)

Disease associations

OMIM: gene MIM:193065 | disease phenotypes: MIM:611407, MIM:613255, MIM:192600, MIM:115195, MIM:603829, MIM:115200, MIM:609620, MIM:142623, MIM:613426, MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy 1W	Strong	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
hypertrophic cardiomyopathy 15	Limited	Autosomal dominant
congenital heart disease	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Disputed	AD
dilated cardiomyopathy 1W	Strong	AD
congenital heart disease	No Known Disease Relationship	UD

Mondo (18): dilated cardiomyopathy 1W (MONDO:0012667), hypertrophic cardiomyopathy 15 (MONDO:0013200), dilated cardiomyopathy (MONDO:0005021), cardiomyopathy (MONDO:0004994), familial hypertrophic cardiomyopathy (MONDO:0024573), hypertrophic cardiomyopathy (MONDO:0005045), hypertrophic cardiomyopathy 2 (MONDO:0007266), ventricular fibrillation, paroxysmal familial, type 1 (MONDO:0011376), long QT syndrome (MONDO:0002442), familial dilated cardiomyopathy (MONDO:0016333), short QT syndrome (MONDO:0000453), ventricular tachycardia (MONDO:0005477), Hirschsprung disease (MONDO:0018309), dilated cardiomyopathy 1S (MONDO:0013262), Wolff-Parkinson-White syndrome (MONDO:0008685)

Orphanet (12): Familial isolated dilated cardiomyopathy (Orphanet:154), Dilated cardiomyopathy (Orphanet:217604), Rare cardiomyopathy (Orphanet:167848), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Rare hypertrophic cardiomyopathy (Orphanet:217569), Idiopathic ventricular fibrillation (Orphanet:228140), Familial dilated cardiomyopathy (Orphanet:217607), Congenital short QT syndrome (Orphanet:51083), Hirschsprung disease (Orphanet:388), Left ventricular noncompaction (Orphanet:54260), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

27 total (28 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001727	Thromboembolic stroke
HP:0002092	Pulmonary arterial hypertension
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0006685	Endocardial fibrosis
HP:0011462	Young adult onset
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012664	Reduced left ventricular ejection fraction
HP:0012764	Orthopnea
HP:0025169	Left ventricular systolic dysfunction
HP:0031318	Myofiber disarray
HP:0031319	Cardiomyocyte hypertrophy
HP:0031992	Apical hypertrophic cardiomyopathy
HP:0032092	Left ventricular outflow tract obstruction
HP:0033755	Increased left ventricular end-diastolic volume
HP:0034313	Hyperdynamic left ventricular ejection fraction
HP:0100578	Lipoatrophy
HP:0001716	Wolff-Parkinson-White syndrome

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002030_4	Primary tooth development (time to first tooth eruption)	2.000000e-08
GCST002031_4	Primary tooth development (number of teeth)	8.000000e-16
GCST006008_2	Left ventricular internal dimension in diastole	1.000000e-08
GCST008309_5	Cardiac troponin-I levels	3.000000e-09
GCST010002_291	Refractive error	2.000000e-09
GCST010796_1784	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1785	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_1786	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008204	left ventricular diastolic function measurement
EFO:0010071	cardiac troponin I measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
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
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C563538	Cardiomyopathy, Dilated, 1s (supp.)
C566954	Cardiomyopathy, Dilated, 1w (supp.)
C567681	Cardiomyopathy, Familial Hypertrophic, 15 (supp.)
C566171	Cardiomyopathy, Familial Hypertrophic, 2 (supp.)
C580439	Short Qt Syndrome (supp.)
C567851	Ventricular Fibrillation, Paroxysmal Familial, 1 (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295723 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.45	Kd	358.9	nM	CHEMBL3752910
6.45	ED50	358.9	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149758: Binding affinity to human VCL incubated for 45 mins by Kinobead based pull down assay	kd	0.3589	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	3
bisphenol A	decreases expression, decreases reaction	2
mono-(2-ethylhexyl)phthalate	decreases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Dexamethasone	decreases expression, affects cotreatment, increases expression, decreases reaction	2
Estradiol	affects expression, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance, decreases expression	2
Smoke	affects localization, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
trichostatin A	affects expression	1
sodium arsenite	decreases reaction, affects binding	1
cobaltous chloride	decreases expression	1
coumarin	increases phosphorylation	1
beta-glycerophosphoric acid	affects cotreatment, increases expression, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
microcystin RR	decreases expression, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119043	Binding	Binding affinity to VCL in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1CR	Abcam A-431 VCL KO	Cancer cell line	Female
CVCL_B2KY	Abcam HeLa VCL KO	Cancer cell line	Female
CVCL_B7T1	ZZUNEUi026-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
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
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation