VGLL3 Gene

HGNC Family	Vestigial-like family (VGLL)
Name	vestigial-like family member 3
Description	Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVGLL3 is a transcriptional co‐factor that modulates TEAD‐dependent gene regulation across several biological contexts. In soft tissue sarcomas, genomic amplification of the VGLL3 locus is tightly linked to increased expression, and functional studies indicate that VGLL3, together with its paralog YAP1, acts as a co‐activator of TEAD transcription factors, thereby contributing to tumor cell proliferation, migration, and ultimately oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations in mesenchymal lineages have revealed that VGLL3 functions as an inhibitor of adipogenesis. Expression of VGLL3 is downregulated during adipocyte differentiation, and experimental overexpression results in suppressed differentiation of preadipocytes, while knockdown promotes adipogenesis. In this setting, VGLL3 appears to influence mesenchymal cell fate decisions by favoring osteogenic or chondrogenic gene expression programs over adipocyte formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the immune system, a distinct female‐biased transcriptomic signature associated with susceptibility to autoimmune diseases has been identified, and VGLL3 emerges as a key upstream regulator of this signature. Its elevated, female–biased expression correlates with upregulation of inflammatory networks seen in conditions such as lupus, scleroderma, and Sjögren's syndrome, highlighting a previously unrecognized role for VGLL3 in modulating immune responses and promoting autoimmunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn skeletal muscle, VGLL3 is expressed at low levels in healthy tissue, but its expression increases during hypertrophy and regeneration, as well as in various muscle pathologies. Proteomic and functional analyses demonstrate that VGLL3 binds TEAD family members, and its overexpression promotes myogenic differentiation while concurrently repressing key elements of the Hippo negative-feedback loop. This suggests that VGLL3 operates within the Hippo signaling network to regulate muscle fiber differentiation and repair processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in tumor cells, elevated VGLL3 levels have been shown to enhance proliferation. Through its partnership with TEAD factors, VGLL3 drives expression of Hippo pathway components such as LATS2 and AMOTL2, leading to inactivation of YAP/TAZ and thereby modulating cell proliferation. Conversely, knockdown experiments in malignant breast and osteosarcoma cells underline the significance of VGLL3-mediated Hippo activation in sustaining tumor cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zofia Hélias-Rodzewicz, Gaëlle Pérot, Frédéric Chibon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20825"}], "href": "https://doi.org/10.1002/gcc.20825"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20842732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20842732"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniel S Halperin, Calvin Pan, Aldons J Lusis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vestigial-like 3 is an inhibitor of adipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M032755"}], "href": "https://doi.org/10.1194/jlr.M032755"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23152581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23152581"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rui Han, Fei Sun, Jihui Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Trace Na"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "CO"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "3"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " Addition to Limestone Inducing High-Capacity SO"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " Capture."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Sci Technol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.est.7b04141"}], "href": "https://doi.org/10.1021/acs.est.7b04141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28992404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28992404"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nicolas Figeac, Abdalla D Mohamed, Congshan Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.225946"}], "href": "https://doi.org/10.1242/jcs.225946"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31138678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31138678"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Naoto Hori, Kazuyuki Okada, Yuki Takakura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vestigial-like family member 3 (VGLL3), a cofactor for TEAD transcription factors, promotes cancer cell proliferation by activating the Hippo pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.012781"}], "href": "https://doi.org/10.1074/jbc.RA120.012781"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32385107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32385107"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tim D Holmes, Ram Vinay Pandey, Eric Y Helm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciimmunol.abc9801"}], "href": "https://doi.org/10.1126/sciimmunol.abc9801"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33712472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33712472"}]}]}]}
Synonyms	VGL3, VGL-3
Proteins	VGLL3_HUMAN
NCBI Gene ID	389136
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

VGLL3 has 5,588 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 106 datasets.

Click the + buttons to view associations for VGLL3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

VGLL3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of VGLL3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of VGLL3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of VGLL3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of VGLL3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of VGLL3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of VGLL3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of VGLL3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of VGLL3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of VGLL3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of VGLL3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of VGLL3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of VGLL3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with VGLL3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of VGLL3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of VGLL3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of VGLL3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of VGLL3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing VGLL3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of VGLL3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing VGLL3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing VGLL3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing VGLL3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with VGLL3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with VGLL3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of VGLL3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with VGLL3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with VGLL3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with VGLL3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by VGLL3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with VGLL3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with VGLL3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with VGLL3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with VGLL3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with VGLL3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with VGLL3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at VGLL3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of VGLL3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of VGLL3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing VGLL3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with VGLL3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.