VCL

vinculin

Basic information

Region (hg38): 10:73995193-74121363

Links

ENSG00000035403

∙ NCBI:7414 ∙ OMIM:193065 ∙ HGNC:12665 ∙ Uniprot:P18206 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hypertrophic cardiomyopathy 15 (Limited), mode of inheritance: AD
familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
dilated cardiomyopathy 1W (Limited), mode of inheritance: AD
hypertrophic cardiomyopathy 15 (Limited), mode of inheritance: AD
dilated cardiomyopathy 1W (Strong), mode of inheritance: AD
hypertrophic cardiomyopathy 15 (Limited), mode of inheritance: AD
hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
dilated cardiomyopathy (Moderate), mode of inheritance: AD
dilated cardiomyopathy 1W (Moderate), mode of inheritance: AD
hypertrophic cardiomyopathy 15 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic 15; Cardiomyopathy, dilated, 1W	AD	Cardiovascular	Surveillance (including with echocardiography, as asymptomatic individuals with variants have been found to have detectable disease prior to clinical presentation), preventive measures, and early medical management may be helpful to help decrease morbidity and mortality related to cardiomyopathy	Cardiovascular	11815424; 16712796; 16236538

ClinVar

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

Dilated_cardiomyopathy_1W (1175 variants)
Cardiovascular_phenotype (626 variants)
not_provided (303 variants)
not_specified (174 variants)
Hypertrophic_cardiomyopathy_15 (118 variants)
Cardiomyopathy (69 variants)
VCL-related_disorder (27 variants)
Primary_dilated_cardiomyopathy (20 variants)
Hypertrophic_cardiomyopathy_2 (7 variants)
Hypertrophic_cardiomyopathy (6 variants)
Wolff-Parkinson-White_pattern (3 variants)
Primary_familial_hypertrophic_cardiomyopathy (3 variants)
Long_QT_syndrome (2 variants)
Primary_familial_dilated_cardiomyopathy (2 variants)
Congestive_heart_failure (1 variants)
Dilated_Cardiomyopathy,_Dominant (1 variants)
Sudden_unexplained_death (1 variants)
Aborted_sudden_cardiac_death (1 variants)
Short_QT_syndrome (1 variants)
Dilated_cardiomyopathy_with_left_ventricular_noncompaction (1 variants)
Ventricular_tachycardia (1 variants)
Dilated_cardiomyopathy_1S (1 variants)
Ventricular_fibrillation,_paroxysmal_familial,_type_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VCL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014000.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	371 clinvar	7 clinvar	385
missense		1 clinvar	726 clinvar	31 clinvar	2 clinvar	760
nonsense		2 clinvar	22 clinvar			24
start loss						0
frameshift	1 clinvar	2 clinvar	31 clinvar			34
splice donor/acceptor (+/-2bp)		2 clinvar	20 clinvar			22
Total	1	7	806	402	9

Highest pathogenic variant AF is 0.000019827894

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VCL	protein_coding	protein_coding	ENST00000211998	22	122047

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0468	0.953	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.71	443	635	0.698	0.0000384	7375
Missense in Polyphen		222	378.75	0.58614		4409
Synonymous	1.46	201	229	0.878	0.0000137	2288
Loss of Function	5.14	14	55.2	0.254	0.00000328	638

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000850	0.000850
Ashkenazi Jewish	0.000794	0.000794
East Asian	0.000218	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000218	0.000217
South Asian	0.000133	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:20484056}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:11815424, ECO:0000269|PubMed:16236538}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:16712796}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Focal adhesion - Homo sapiens (human);Adherens junction - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Integrin-mediated Cell Adhesion;Primary Focal Segmental Glomerulosclerosis FSGS;Focal Adhesion;VEGFA-VEGFR2 Signaling Pathway;Regulation of Actin Cytoskeleton;Smooth Muscle Contraction;MAP2K and MAPK activation;Neutrophil degranulation;Disease;Signal Transduction;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;integrin signaling pathway;rho cell motility signaling pathway;Innate Immune System;Immune System;Muscle contraction;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Integrin;EGFR1;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Stabilization and expansion of the E-cadherin adherens junction;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Signaling events mediated by focal adhesion kinase;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis;RhoA signaling pathway (Consensus)

Intolerance Scores

loftool: 0.602
rvis_EVS: -1.79
rvis_percentile_EVS: 2.23

Haploinsufficiency Scores

pHI: 0.845
hipred: Y
hipred_score: 0.639
ghis: 0.605

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: H
gene_indispensability_pred: E
gene_indispensability_score: 0.912

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vcl
Phenotype: digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name: vclb
Affected structure: fibroblast
Phenotype tag: abnormal
Phenotype quality: accumulation

Gene ontology

Biological process: morphogenesis of an epithelium;platelet degranulation;muscle contraction;cell adhesion;cell-matrix adhesion;lamellipodium assembly;negative regulation of cell migration;adherens junction assembly;protein localization to cell surface;apical junction assembly;neutrophil degranulation;axon extension;platelet aggregation;epithelial cell-cell adhesion
Cellular component: podosome;extracellular region;cytosol;cytoskeleton;cell-cell junction;adherens junction;cell-cell adherens junction;fascia adherens;focal adhesion;cell-substrate junction;protein-containing complex;secretory granule lumen;specific granule lumen;sarcolemma;costamere;extracellular exosome;extracellular vesicle;ficolin-1-rich granule lumen
Molecular function: dystroglycan binding;actin binding;structural molecule activity;protein binding;beta-catenin binding;ubiquitin protein ligase binding;alpha-catenin binding;cadherin binding