VCL (Vinculin) Gene: Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the VCL gene, encoding vinculin, a key cytoskeletal protein involved in cell adhesion and migration.
Gene Information Card
| Symbol | VCL |
|---|---|
| Full Name | Vinculin |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.2 |
| NCBI Gene ID | 7414 ncbi.nlm.nih.gov/gene/7414 |
| Ensembl ID | ENSG00000035403 |
| UniProt ID | P18206 |
| OMIM ID | 193065 |
| HGNC ID | 12665 |
| Aliases | MV, CMD1W, CMH15, HEL113 |
Description
The VCL gene encodes vinculin, a 117 kDa cytoskeletal protein that is a critical component of focal adhesions and adherens junctions. Vinculin links integrin adhesion molecules to the actin cytoskeleton, regulating cell adhesion, migration, and mechanotransduction. Alternative splicing produces two isoforms: vinculin (meta-vinculin) and a shorter isoform. Mutations in VCL are associated with dilated cardiomyopathy (CMD1W) and hypertrophic cardiomyopathy (CMH15). Altered expression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy 1W (CMD1W) | Loss-of-function mutations disrupt vinculin-mediated force transmission in cardiac myocytes, impairing contractility. | OMIM #193065; ClinVar |
| Hypertrophic cardiomyopathy 15 (CMH15) | Missense mutations alter vinculin structure, leading to abnormal sarcomere assembly and hypertrophy. | OMIM #193065; ClinVar |
| Colorectal cancer | Reduced vinculin expression correlates with increased metastasis; vinculin loss promotes cell migration. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 78.2 | High |
| Skeletal muscle | 62.5 | High |
| Smooth muscle | 55.1 | High |
| Lung | 18.3 | Medium |
| Liver | 12.4 | Medium |
| Brain | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 45.2 | Cervical cancer cell line |
| A549 | 38.9 | Lung carcinoma cell line |
| HUVEC | 52.1 | Endothelial cell line |
| MCF7 | 29.8 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.970C>T (p.Arg324Trp) | Missense | Rare | Associated with hypertrophic cardiomyopathy; disrupts actin binding |
| c.1456G>A (p.Glu486Lys) | Missense | Rare | Linked to dilated cardiomyopathy; reduces focal adhesion stability |
| c.1915_1917del (p.Lys639del) | In-frame deletion | Rare | Reported in dilated cardiomyopathy; impairs vinculin head-tail interaction |
| c.2176C>T (p.Arg726Trp) | Missense | Rare | Found in hypertrophic cardiomyopathy; alters talin binding |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., truncations, deletions) reduce vinculin expression or disrupt actin/talin binding, impairing cell adhesion and cardiac contractility, leading to dilated cardiomyopathy.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in VCL.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg324Trp) may act as dominant-negative by forming non-functional dimers, interfering with wild-type vinculin function in cardiomyocytes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Focal adhesion (KEGG: hsa04510)
• Adherens junction (KEGG: hsa04520)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Integrin signaling pathway (Reactome: R-HSA-354192)
Protein Summary
Vinculin is a 1066-amino acid protein with a globular head domain (Vh1), a proline-rich linker, and a C-terminal tail domain (Vt). The head domain binds talin and α-actinin, while the tail binds actin and paxillin. Vinculin exists in an autoinhibited conformation; upon activation, it stabilizes focal adhesions and transmits mechanical forces. Meta-vinculin, the smooth muscle isoform, contains an additional 68-residue insert in the tail domain, enhancing actin binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VCL Knockout HEK293 Cell Line | EDJ-KQ2846 | Human | 7414 | Details Get a Quote |
| VCL Knockout A-549 Cell Line | EDJ-KQ23845 | Human | 7414 | Details Get a Quote |
| VCL Knockout HCT 116 Cell Line | EDJ-KQ23846 | Human | 7414 | Details Get a Quote |
| VCL Knockout HeLa Cell Line | EDJ-KQ23847 | Human | 7414 | Details Get a Quote |
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