Details for: VGLL2

Gene ID: 245806

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: VGLL2

Ensembl ID: ENSG00000170162

Description: vestigial like family member 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • muscle cell CL0000187
    CSI 3.83
    rCSI 7.87%
    PRS 100

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Size: Proportional to Target Cell CSI magnitude
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [VGLL2](/details-gene/245806) (Vestigial-Like Family Member 2) is a protein-coding gene that functions as a transcriptional coactivator. It plays a highly specialized role in the development and differentiation of skeletal muscle. This function is underscored by its exceptionally specific and significant expression in [muscle cell](/details-cell/CL0000187)s. Mechanistically, [VGLL2](/details-gene/245806) acts by binding to and enhancing the activity of key myogenic transcription factors, thereby driving the genetic programs essential for muscle tissue formation [Link](https://doi.org/10.1074/jbc.m206858200). Its restricted expression pattern and critical role in myogenesis suggest it is a key regulator of muscle lineage identity. ## Cellular Roles and Expression Landscape The expression profile of [VGLL2](/details-gene/245806) is characterized by its remarkable specificity for the muscle lineage. - **Overall Context:** Analysis reveals that [VGLL2](/details-gene/245806) is a top marker gene almost exclusively for [muscle cell](/details-cell/CL0000187) (CSI: 3.83). This high significance indicates that its expression is a defining feature of this cell type. This finding is strongly supported by research identifying its predominant expression within the skeletal muscle lineage, where it is also known as VITO-1 [Link](https://doi.org/10.1016/s0925-4773(02)00386-6). The data suggests that [VGLL2](/details-gene/245806) is not a broadly expressed regulatory factor but rather a specialist, whose primary biological footprint is confined to muscle tissue. ## Pathways and Molecular Function The function of [VGLL2](/details-gene/245806) is intimately linked to the transcriptional control of muscle development. Gene Ontology annotations place it within the `nucleus` ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) and `cytoplasm` ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)), consistent with its role as a transcriptional regulator that may shuttle between compartments. Its core molecular function is `transcription coactivator activity` ([GO:0003713](https://www.ebi.ac.uk/QuickGO/term/GO:0003713)) and `protein binding` ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). This is directly realized through its involvement in the biological process of `skeletal muscle tissue development` ([GO:0007519](https://www.ebi.ac.uk/QuickGO/term/GO:0007519)). Seminal research has shown that [VGLL2](/details-gene/245806) functions as a cofactor for the TEF-1 (TEAD) and MEF2 families of transcription factors, both of which are master regulators of myogenesis. By interacting with these factors, [VGLL2](/details-gene/245806) promotes skeletal muscle differentiation, effectively participating in the `positive regulation of transcription by rna polymerase ii` ([GO:0045944](https://www.ebi.ac.uk/QuickGO/term/GO:0045944)) for muscle-specific genes [Link](https://doi.org/10.1074/jbc.m206858200). ## Research Directions The highly specific role of [VGLL2](/details-gene/245806) in muscle differentiation makes it a compelling subject for research into muscle pathologies and regenerative medicine. ### Proposed Hypotheses 1. **Impaired Muscle Regeneration:** Given its pro-differentiative function, insufficient expression or loss-of-function mutations in [VGLL2](/details-gene/245806) may contribute to the pathology of certain congenital myopathies or muscular dystrophies by impairing the ability of satellite cells (muscle stem cells) to effectively differentiate and repair damaged muscle tissue. 2. **Role in Muscle Atrophy:** The downregulation of [VGLL2](/details-gene/245806) could be a key mechanism in conditions of muscle atrophy, such as sarcopenia or cachexia, where the balance shifts away from muscle maintenance and regeneration towards muscle breakdown. ### Key Experiment To test the hypothesis that [VGLL2](/details-gene/245806) is critical for muscle regeneration (Hypothesis 1), a robust experimental approach would be to use a conditional knockout mouse model. Specifically, generating a *Vgll2-floxed* mouse crossed with a *Pax7-CreERT2* line would allow for tamoxifen-inducible deletion of [VGLL2](/details-gene/245806) specifically in adult muscle satellite cells. Following deletion, muscle injury could be induced (e.g., via cardiotoxin injection), and the regenerative process could be monitored via histology (measuring regenerating myofiber size), immunofluorescence for myogenic markers, and functional tests of muscle strength. A failure to regenerate efficiently compared to control animals would provide direct evidence for its essential role in muscle repair. ### Therapeutic Potential The function and specificity of [VGLL2](/details-gene/245806) suggest it has significant therapeutic potential. Because it promotes muscle differentiation, it is a candidate for therapies aimed at **activation** or replacement. For conditions involving poor muscle regeneration or wasting, strategies to enhance [VGLL2](/details-gene/245806) function could be beneficial. Its high tissue-specificity is a major advantage, as it would likely minimize off-target effects. Gene therapy approaches using adeno-associated virus (AAV) vectors with muscle-specific promoters to deliver a functional copy of [VGLL2](/details-gene/245806) could be a viable strategy for treating genetic myopathies characterized by impaired differentiation or for combating age-related muscle loss.

Genular Protein ID: 958170167

Symbol: VGLL2_HUMAN

Name: Transcription cofactor vestigial-like protein 2

UniProtKB Accession Codes:

Q8N8G2 Q8WWX1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 2 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12617818

Title: VITO-1, a novel vestigial related protein is predominantly expressed in the skeletal muscle lineage.

PubMed ID: 12617818

DOI: 10.1016/s0925-4773(02)00386-6

PubMed ID: 12376544

Title: Mammalian vestigial-like 2, a cofactor of TEF-1 and MEF2 transcription factors that promotes skeletal muscle differentiation.

PubMed ID: 12376544

DOI: 10.1074/jbc.m206858200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 317
  • Mass: 33426
  • Checksum: 2C08E5D1070FF10D
  • Sequence:
    • MSCLDVMYQV YGPPQPYFAA AYTPYHQKLA YYSKMQEAQE CNASPSSSGS GSSSFSSQTP 
ASIKEEEGSP EKERPPEAEY INSRCVLFTY FQGDISSVVD EHFSRALSQP SSYSPSCTSS 
KAPRSSGPWR DCSFPMSQRS FPASFWNSAY QAPVPPPLGS PLATAHSELP FAAADPYSPA 
ALHGHLHQGA TEPWHHAHPH HAHPHHPYAL GGALGAQAAP YPRPAAVHEV YAPHFDPRYG 
PLLMPAASGR PARLATAPAP APGSPPCELS GKGEPAGAAW AGPGGPFASP SGDVAQGLGL 
SVDSARRYSL CGASLLS