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    VGLL4 vestigial like family member 4 [ Homo sapiens (human) ]

    Gene ID: 9686, updated on 3-Apr-2024

    Summary

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    Official Symbol
    VGLL4provided by HGNC
    Official Full Name
    vestigial like family member 4provided by HGNC
    Primary source
    HGNC:HGNC:28966
    See related
    Ensembl:ENSG00000144560 MIM:618692; AllianceGenome:HGNC:28966
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    VGL-4
    Summary
    Predicted to enable transcription coactivator binding activity. Involved in negative regulation of Wnt signaling pathway; negative regulation of cell growth; and negative regulation of hippo signaling. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in ovary (RPKM 26.1), thyroid (RPKM 18.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3p25.3-p25.2
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (11556067..11721815, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (11551371..11717542, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (11597541..11762013, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19429 Neighboring gene ribosomal protein L13a pseudogene 27 Neighboring gene autophagy related 7 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:11405755-11406954 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:11521898-11522503 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:11574579-11575079 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11586483-11587050 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:11587827-11588328 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:11588329-11588828 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:11616238-11617058 Neighboring gene CSTB pseudogene 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11624893-11625731 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11634691-11635222 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11635223-11635753 Neighboring gene Sharpr-MPRA regulatory region 8254 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr3:11642749-11643347 and GRCh37_chr3:11643348-11643945 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11650998-11651770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19431 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11680477-11681428 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19432 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19433 Neighboring gene Sharpr-MPRA regulatory region 9131 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14062 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14063 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19434 Neighboring gene TAM41 mitochondrial translocator assembly and maintenance homolog Neighboring gene Sharpr-MPRA regulatory region 5418 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:11826643-11827198 Neighboring gene FANCD2 pseudogene 2 Neighboring gene CYCS pseudogene 12

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Validation of Osteogenic Properties of Cytochalasin D by High-Resolution RNA-Sequencing in Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissues. Samsonraj RM, et al. Stem Cells Dev, 2018 Aug 15. PMID 29882479, Free PMC Article
    2. VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer. Zhang Y, et al. Sci Rep, 2017 Jul 21. PMID 28733631, Free PMC Article
    3. Downregulation of VGLL4 in the progression of esophageal squamous cell carcinoma. Jiang W, et al. Tumour Biol, 2015 Feb. PMID 25352025
    4. Characterization of genetic variation in the VGLL4 gene in anorexia nervosa. Clarke TK, et al. Psychiatr Genet, 2014 Aug. PMID 24983835, Free PMC Article
    5. Brief report: VGLL4 is a novel regulator of survival in human embryonic stem cells. Tajonar A, et al. Stem Cells, 2013 Dec. PMID 23765749, Free PMC Article

    See all (53) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2.
      Title: VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2.
    2. Biochemical properties of VGLL4 from Homo sapiens and Tgi from Drosophila melanogaster and possible biological implications.
      Title: Biochemical properties of VGLL4 from Homo sapiens and Tgi from Drosophila melanogaster and possible biological implications.
    3. The lncRNA MEG3/miR-16-5p/VGLL4 regulatory axis is involved in etoposide-induced senescence of tumor cells.
      Title: The lncRNA MEG3/miR-16-5p/VGLL4 regulatory axis is involved in etoposide-induced senescence of tumor cells.
    4. HOXB13 suppresses proliferation, migration and invasion, and promotes apoptosis of gastric cancer cells through transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway.
      Title: HOXB13 suppresses proliferation, migration and invasion, and promotes apoptosis of gastric cancer cells through transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway.
    5. VGLL4 inhibits YAP1/TEAD signaling to suppress the epidermal squamous cell carcinoma cancer phenotype.
      Title: VGLL4 inhibits YAP1/TEAD signaling to suppress the epidermal squamous cell carcinoma cancer phenotype.
    6. LINC00641 regulates prostate cancer cell growth and apoptosis via the miR-365a-3p/VGLL4 axis.
      Title: LINC00641 regulates prostate cancer cell growth and apoptosis via the miR-365a-3p/VGLL4 axis.
    7. VGLL4 interacts with STAT3 to function as a tumor suppressor in triple-negative breast cancer
      Title: VGLL4 interacts with STAT3 to function as a tumor suppressor in triple-negative breast cancer.
    8. Identification of VGLL4 as an important regulator of PD-L1 expression and a central role of VGLL4 and YAP in the regulation of tumor immunity.
      Title: Loss of VGLL4 suppresses tumor PD-L1 expression and immune evasion.
    9. our RNA-seq analyses suggest that while the stimulatory effects of CytoD on osteogenesis are pleiotropic and depend on the biological state of the cell type, a small group of genes including VGLL4 may contribute to MSC commitment toward the bone lineage.
      Title: Validation of Osteogenic Properties of Cytochalasin D by High-Resolution RNA-Sequencing in Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissues.
    10. Data report that VGLL4 functions as a suppressor of breast tumor (BC) growth and progression. Its low expression correlated with a poor prognosis. Its ectopic expression in BC cell lines reduced cell proliferation, migration, and tumor formation in xenograft mouse model. VGLL4 interacts with TEAD1 via its second TEAD-interacting domain, antagonizing YAP-dependent tumor growth.
      Title: VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa.
    EBI GWAS Catalog
    Common variants in left/right asymmetry genes and pathways are associated with relative hand skill.
    EBI GWAS Catalog
    Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0121

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of DNA-templated transcription IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cardiac muscle cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of cell growth IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of hippo signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of hippo signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of protein catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    transcription cofactor vestigial-like protein 4
    Names
    Vestigial-like 4
    vestigial like 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001128219.3 → NP_001121691.1  transcription cofactor vestigial-like protein 4 isoform a

      See identical proteins and their annotated locations for NP_001121691.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      BU682809, D50911, DA383197, DA386938, DR159250
      Consensus CDS
      CCDS46754.1
      UniProtKB/TrEMBL
      G5E9M7
      Related
      ENSP00000404251.2, ENST00000430365.7
      Conserved Domains (2) summary
      smart00711
      Location:240 → 255
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:14 → 230
      VGLL4; Transcription cofactor vestigial-like protein 4

    2. NM_001128220.3 → NP_001121692.1  transcription cofactor vestigial-like protein 4 isoform c

      See identical proteins and their annotated locations for NP_001121692.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AK307708, BU682809, D50911
      Consensus CDS
      CCDS46755.1
      UniProtKB/TrEMBL
      Q0H0I7
      Related
      ENSP00000416615.2, ENST00000451674.6
      Conserved Domains (2) summary
      smart00711
      Location:154 → 169
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:6 → 144
      VGLL4; Transcription cofactor vestigial-like protein 4

    3. NM_001128221.3 → NP_001121693.1  transcription cofactor vestigial-like protein 4 isoform d

      See identical proteins and their annotated locations for NP_001121693.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (d) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AK308761, BU682809, D50911
      Consensus CDS
      CCDS46756.1
      UniProtKB/TrEMBL
      Q0H0I7
      Related
      ENSP00000402878.2, ENST00000424529.6
      Conserved Domains (2) summary
      smart00711
      Location:150 → 165
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:1 → 140
      VGLL4; Transcription cofactor vestigial-like protein 4

    4. NM_001284390.2 → NP_001271319.1  transcription cofactor vestigial-like protein 4 isoform e

      See identical proteins and their annotated locations for NP_001271319.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (e) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      BC000763, BU682809, D50911, DA383197
      Consensus CDS
      CCDS68343.1
      UniProtKB/TrEMBL
      A0A0A6YYI5
      Related
      ENSP00000413030.2, ENST00000426568.5
      Conserved Domains (2) summary
      smart00711
      Location:239 → 254
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:27 → 229
      VGLL4; Transcription cofactor vestigial-like protein 4

    5. NM_001284391.1 → NP_001271320.1  transcription cofactor vestigial-like protein 4 isoform f

      See identical proteins and their annotated locations for NP_001271320.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (f) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AC022001, AI809612, AK300344, BU682809, D50911, DA383197
      Consensus CDS
      CCDS68342.1
      UniProtKB/TrEMBL
      A0A024R2F0, A0A9K3Y712, G5E9M9, Q0H0I7
      Related
      ENSP00000404624.1, ENST00000413604.5
      Conserved Domains (2) summary
      smart00711
      Location:175 → 190
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:1 → 165
      VGLL4; Transcription cofactor vestigial-like protein 4

    6. NM_014667.4 → NP_055482.2  transcription cofactor vestigial-like protein 4 isoform b

      See identical proteins and their annotated locations for NP_055482.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AK130542, BU682809, D50911, DA383197
      Consensus CDS
      CCDS2606.1
      UniProtKB/TrEMBL
      A0A075B6E4
      Related
      ENSP00000273038.3, ENST00000273038.7
      Conserved Domains (2) summary
      smart00711
      Location:234 → 249
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:8 → 223
      VGLL4; Transcription cofactor vestigial-like protein 4

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      11556067..11721815 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047449259.1 → XP_047305215.1  transcription cofactor vestigial-like protein 4 isoform X1

    2. XM_024453835.2 → XP_024309603.1  transcription cofactor vestigial-like protein 4 isoform X3

      UniProtKB/TrEMBL
      A0A075B6E4
      Conserved Domains (2) summary
      smart00711
      Location:234 → 249
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:8 → 223
      VGLL4; Transcription cofactor vestigial-like protein 4

    3. XM_024453836.2 → XP_024309604.1  transcription cofactor vestigial-like protein 4 isoform X3

      UniProtKB/TrEMBL
      A0A075B6E4
      Conserved Domains (2) summary
      smart00711
      Location:234 → 249
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:8 → 223
      VGLL4; Transcription cofactor vestigial-like protein 4

    4. XM_047449260.1 → XP_047305216.1  transcription cofactor vestigial-like protein 4 isoform X2

    5. XM_047449261.1 → XP_047305217.1  transcription cofactor vestigial-like protein 4 isoform X4

      UniProtKB/TrEMBL
      A0A024R2F0, A0A9K3Y712, G5E9M9

    6. XM_011534269.2 → XP_011532571.1  transcription cofactor vestigial-like protein 4 isoform X4

      See identical proteins and their annotated locations for XP_011532571.1

      UniProtKB/TrEMBL
      A0A024R2F0, A0A9K3Y712, G5E9M9, Q0H0I7
      Conserved Domains (2) summary
      smart00711
      Location:175 → 190
      TDU; Short repeats in human TONDU, fly vestigial and other proteins
      pfam15245
      Location:1 → 165
      VGLL4; Transcription cofactor vestigial-like protein 4

    7. XM_047449262.1 → XP_047305218.1  transcription cofactor vestigial-like protein 4 isoform X5

    8. XM_024453837.2 → XP_024309605.1  transcription cofactor vestigial-like protein 4 isoform X7

      UniProtKB/TrEMBL
      E7EQU6
      Related
      ENSP00000394439.1, ENST00000418000.5
      Conserved Domains (1) summary
      pfam15245
      Location:8 → 204
      VGLL4; Transcription cofactor vestigial-like protein 4

    9. XM_047449263.1 → XP_047305219.1  transcription cofactor vestigial-like protein 4 isoform X6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      11551371..11717542 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054348499.1 → XP_054204474.1  transcription cofactor vestigial-like protein 4 isoform X1

    2. XM_054348501.1 → XP_054204476.1  transcription cofactor vestigial-like protein 4 isoform X3

      UniProtKB/Swiss-Prot
      B4DTS7, J3KN68, Q14135, Q7L5V0, Q9BQ78

    3. XM_054348502.1 → XP_054204477.1  transcription cofactor vestigial-like protein 4 isoform X3

      UniProtKB/Swiss-Prot
      B4DTS7, J3KN68, Q14135, Q7L5V0, Q9BQ78

    4. XM_054348500.1 → XP_054204475.1  transcription cofactor vestigial-like protein 4 isoform X2

    5. XM_054348503.1 → XP_054204478.1  transcription cofactor vestigial-like protein 4 isoform X8

    6. XM_054348507.1 → XP_054204482.1  transcription cofactor vestigial-like protein 4 isoform X8

    7. XM_054348504.1 → XP_054204479.1  transcription cofactor vestigial-like protein 4 isoform X5

    8. XM_054348506.1 → XP_054204481.1  transcription cofactor vestigial-like protein 4 isoform X7

    9. XM_054348505.1 → XP_054204480.1  transcription cofactor vestigial-like protein 4 isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14135.4 GenPept UniProtKB/Swiss-Prot:Q14135

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