VGLL4
Vestigial Like Family Member 4: A Transcriptional Cofactor Regulating Hippo Signaling and Cancer
Gene Information Card
| Symbol | VGLL4 |
|---|---|
| Full Name | Vestigial Like Family Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p25.2 |
| NCBI Gene ID | 9686 ncbi.nlm.nih.gov/gene/9686 |
| Ensembl ID | ENSG00000144560 |
| UniProt ID | Q14135 |
| OMIM ID | 618704 |
| HGNC ID | 28966 |
| Aliases | Vgl-4, VGLL4, vestigial-like 4 |
Description
VGLL4 (Vestigial Like Family Member 4) encodes a transcriptional cofactor that interacts with TEAD transcription factors to regulate Hippo signaling pathway target genes. It acts as a tumor suppressor by competing with YAP/TAZ for TEAD binding, thereby inhibiting cell proliferation and promoting differentiation. VGLL4 is involved in development, tissue homeostasis, and its dysregulation is implicated in multiple cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | Loss of VGLL4 expression or function leads to increased YAP/TAZ activity, promoting uncontrolled cell growth. | COSMIC, ClinVar, literature |
| Gastric cancer | VGLL4 downregulation correlates with poor prognosis; acts as a tumor suppressor via TEAD inhibition. | PMID: 25624456, COSMIC |
| Lung cancer | VGLL4 mutations or reduced expression contribute to oncogenic Hippo pathway activation. | COSMIC, ClinVar |
| Colorectal cancer | VGLL4 loss enhances Wnt/β-catenin signaling and tumor progression. | PMID: 28991257 |
| Hepatocellular carcinoma | VGLL4 suppresses tumor growth by inhibiting TEAD-mediated transcription. | PMID: 27565344 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 8.2 | Medium |
| Liver | 6.5 | Medium |
| Stomach | 5.1 | Low |
| Colon | 4.8 | Low |
| Breast | 3.9 | Low |
| Kidney | 7.3 | Medium |
| Heart | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung) | 6.0 | Moderate expression |
| HepG2 (liver) | 7.5 | Moderate-high expression |
| MCF7 (breast) | 3.2 | Low expression |
| HeLa (cervical) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163*) | Nonsense | <0.1% | Loss of function; truncated protein |
| c.632G>A (p.Arg211Gln) | Missense | <0.1% | Unknown functional impact |
| c.1015_1016insA (p.Thr339Asnfs*2) | Frameshift | <0.1% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg163*, p.Thr339Asnfs*2) result in truncated or absent protein, reducing TEAD inhibition and promoting oncogenic signaling.
Gain of Function (GOF)
No gain-of-function mutations reported in VGLL4.
Dominant Negative (DN)
No dominant-negative mutations described for VGLL4.
View complete mutation data：
Gene Ontology (GO)
| • transcription coactivator activity | • transcription corepressor activity |
| • protein binding | • nucleus |
| • cytoplasm | • regulation of transcription by RNA polymerase II |
| • negative regulation of cell population proliferation | • Hippo signaling |
Pathways
• Hippo signaling pathway
• TEAD transcription factor network
• Regulation of organ growth
Protein Summary
VGLL4 is a 299-amino-acid protein containing a Tondu (TDU) domain that mediates interaction with TEAD transcription factors. It functions as a transcriptional cofactor that can both activate and repress gene expression depending on context. By competing with YAP/TAZ for TEAD binding, VGLL4 acts as a critical negative regulator of the Hippo pathway, suppressing cell proliferation and tumorigenesis. The protein is predominantly nuclear but can also localize to the cytoplasm.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VGLL4 Knockout HEK293 Cell Line | EDJ-KQ2637 | Human | 9686 | Details Get a Quote |
| VGLL4 Knockout A-549 Cell Line | EDJ-KQ23394 | Human | 9686 | Details Get a Quote |
| VGLL4 Knockout HCT 116 Cell Line | EDJ-KQ23395 | Human | 9686 | Details Get a Quote |
| VGLL4 Knockout HeLa Cell Line | EDJ-KQ23396 | Human | 9686 | Details Get a Quote |
