VCL

Chr 10AD

vinculin

Also known as: CMD1W, CMH15, HEL114, MV, MVCL, VINC

NCBI Gene: 7414 ENSG00000035403 UniProt: P18206 OMIM: 193065

Vinculin is an actin filament-binding protein that regulates cell-matrix and cell-cell adhesion and potentiates mechanosensing by the E-cadherin complex. Mutations cause autosomal dominant dilated cardiomyopathy type 1W and hypertrophic cardiomyopathy type 15, both affecting cardiac muscle function. The gene is highly constrained against loss-of-function variants (LOEUF 0.396), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1WMIM #611407

Cardiomyopathy, hypertrophic, 15MIM #613255

UniProtCardiomyopathy, familial hypertrophic, 15

Clinical highlights

Gene-disease validity (ClinGen)

hypertrophic cardiomyopathy · ADDisputedevidence questions this relationship3 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.40

LOEUF

Multiple*

Mechanism· predicted