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VGLL1

gene
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Also known as TONDUTDU

Summary

VGLL1 (vestigial like family member 1, HGNC:20985) is a protein-coding gene on chromosome Xq26.3, encoding Transcription cofactor vestigial-like protein 1 (Q99990). May act as a specific coactivator for the mammalian TEFs.

The protein encoded by this gene binds proteins of the TEA domain family of transcription factors (TEFs) through the Vg (vestigial) homology region found in its N-terminus. It may thus function as a specific coactivator for the mammalian TEFs.

Source: NCBI Gene 51442 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 58 total
  • MANE Select transcript: NM_016267

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:20985
Approved symbolVGLL1
Namevestigial like family member 1
LocationXq26.3
Locus typegene with protein product
StatusApproved
AliasesTONDU, TDU
Ensembl geneENSG00000102243
Ensembl biotypeprotein_coding
OMIM300583
Entrez51442

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370634, ENST00000440515, ENST00000456412, ENST00000470358, ENST00000872080, ENST00000872081, ENST00000872082

RefSeq mRNA: 1 — MANE Select: NM_016267 NM_016267

CCDS: CCDS14658

Canonical transcript exons

ENST00000370634 — 5 exons

ExonStartEnd
ENSE00000677012136548589136549008
ENSE00000677013136550768136550821
ENSE00001029091136532215136532296
ENSE00001453195136535996136536234
ENSE00003843261136556451136556799

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 97.66.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3478 / max 888.3249, expressed in 210 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
1977062.2455172
1977030.468375
1977070.290666
1977040.180748
1977050.123046
1977080.02405
1977090.01586

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
placentaUBERON:000198797.66gold quality
amniotic fluidUBERON:000017395.17gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047388.15gold quality
palpebral conjunctivaUBERON:000181288.04gold quality
urinary bladderUBERON:000125575.30gold quality
deciduaUBERON:000245075.18gold quality
metanephros cortexUBERON:001053374.02gold quality
lower esophagus mucosaUBERON:003583471.90gold quality
nasal cavity epitheliumUBERON:000538471.73gold quality
minor salivary glandUBERON:000183069.26gold quality
olfactory segment of nasal mucosaUBERON:000538668.86gold quality
mucosa of urinary bladderUBERON:000125968.83silver quality
saliva-secreting glandUBERON:000104466.41gold quality
mouth mucosaUBERON:000372966.23gold quality
buccal mucosa cellCL:000233666.12silver quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099165.57gold quality
gluteal muscleUBERON:000200064.33gold quality
right lungUBERON:000216764.11gold quality
nasal cavity mucosaUBERON:000182662.14gold quality
triceps brachiiUBERON:000150961.96gold quality
urethraUBERON:000005761.32silver quality
germinal epithelium of ovaryUBERON:000130459.95gold quality
biceps brachiiUBERON:000150759.90gold quality
pituitary glandUBERON:000000759.02gold quality
upper lobe of left lungUBERON:000895258.82gold quality
substantia nigra pars reticulataUBERON:000196658.49gold quality
adult mammalian kidneyUBERON:000008258.33gold quality
upper lobe of lungUBERON:000894858.18gold quality
islet of LangerhansUBERON:000000658.14gold quality
metanephrosUBERON:000008158.11gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

ExperimentMarker?Max mean expression
E-MTAB-6701yes1313.31
E-MTAB-10018yes360.84
E-MTAB-3929yes196.62
E-HCAD-10yes13.42
E-ANND-3yes6.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting VGLL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-126-5P100.0072.713180
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-4455100.0065.481587
HSA-MIR-1213699.9872.815713
HSA-MIR-548N99.9871.944170
HSA-MIR-6825-5P99.9669.813431
HSA-MIR-211099.9666.681930
HSA-MIR-153-5P99.8973.866317
HSA-MIR-129999.7771.242389
HSA-MIR-3150A-3P99.7664.441640
HSA-MIR-6763-5P99.7664.681767
HSA-MIR-548AV-5P99.6070.842107
HSA-MIR-548K99.6070.842107
HSA-MIR-432899.5771.064094
HSA-MIR-1212399.5271.792990
HSA-MIR-467299.5071.582893
HSA-MIR-805499.4870.812084
HSA-MIR-361299.4566.021333
HSA-MIR-65099.4565.771309
HSA-MIR-452-3P99.0166.251241
HSA-MIR-619-5P98.5764.971988
HSA-MIR-367097.8864.39763
HSA-MIR-431497.5067.301369
HSA-MIR-431-5P96.1666.50652
HSA-MIR-2277-3P91.9462.27299

Literature-anchored findings (GeneRIF, showing 8)

  • VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer (PMID:24891455)
  • Novel EWSR1-VGLL1 fusion in a pediatric neuroepithelial neoplasm. (PMID:31925773)
  • A new perspective on the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors. (PMID:33060790)
  • VGLL1 phosphorylation and activation promotes gastric cancer malignancy via TGF-beta/ERK/RSK2 signaling. (PMID:33069758)
  • Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers. (PMID:33087697)
  • Vestigial-like 1 (VGLL1): An ancient co-transcriptional activator linking wing, placenta, and tumor development. (PMID:37004960)
  • VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification. (PMID:38233381)
  • VGLL1 stabilization of cytoplasmic TAZ promotes EGFR expression and maintains tumor initiating cells in breast cancer independent of TEAD. (PMID:38417636)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusVgll1ENSMUSG00000031131
drosophila_melanogastervgFBGN0003975

Paralogs (2): VGLL2 (ENSG00000170162), VGLL3 (ENSG00000206538)

Protein

Protein identifiers

Transcription cofactor vestigial-like protein 1 — Q99990 (reviewed: Q99990)

Alternative names: Protein TONDU

All UniProt accessions (3): Q99990, H0Y5G3, Q5H916

UniProt curated annotations — full annotation on UniProt →

Function. May act as a specific coactivator for the mammalian TEFs.

Subunit / interactions. Interacts with TEFs.

Subcellular location. Nucleus.

Similarity. Belongs to the vestigial family.

RefSeq proteins (1): NP_057351* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR006627TDU_repeatRepeat
IPR011520Vg_famFamily

Pfam: PF07545

UniProt features (5 total): compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q99990-F157.780.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): NKX25_02, MODULE_545, ONDER_CDH1_TARGETS_3_DN, FINAK_BREAST_CANCER_SDPP_SIGNATURE, BRN2_01, SMID_BREAST_CANCER_LUMINAL_A_DN, GOZGIT_ESR1_TARGETS_UP, GNF2_KISS1, BENPORATH_ES_CORE_NINE_CORRELATED, SMID_BREAST_CANCER_RELAPSE_IN_BRAIN_UP, VANTVEER_BREAST_CANCER_ESR1_DN, SMID_BREAST_CANCER_LUMINAL_B_DN, GNF2_TIMP2, GOMF_TRANSCRIPTION_COACTIVATOR_ACTIVITY, LIN_SILENCED_BY_TUMOR_MICROENVIRONMENT

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
DNA-templated transcription2
regulation of DNA-templated transcription2
regulation of gene expression1
regulation of RNA biosynthetic process1
transcription by RNA polymerase II1
positive regulation of RNA biosynthetic process1
transcription coregulator activity1
positive regulation of DNA-templated transcription1
binding1
intracellular membrane-bounded organelle1
nuclear lumen1
cellular anatomical structure1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
VGLL1TEAD1P28347961
VGLL1TEAD4Q15561879
VGLL1VGLL4Q14135826
VGLL1WWTR1Q9GZV5804
VGLL1YAP1P46937728
VGLL1ACTA1P02568650
VGLL1RAD51BO15315571
VGLL1TEAD3Q99594449
VGLL1TEAD2Q15562449
VGLL1CAPN6Q9Y6Q1445
VGLL1MEF2AQ02078436
VGLL1MYH1P12882435
VGLL1MTNR1AP48039431
VGLL1MCATQ8IVS2428
VGLL1VGLL3A8MV65427

IntAct

44 interactions, top by confidence:

ABTypeScore
TEAD3VGLL1psi-mi:“MI:0915”(physical association)0.670
TEAD4VGLL1psi-mi:“MI:0915”(physical association)0.560
HNRNPFVGLL1psi-mi:“MI:0915”(physical association)0.560
PFDN5VGLL1psi-mi:“MI:0915”(physical association)0.560
TRIM23VGLL1psi-mi:“MI:0915”(physical association)0.560
TSSK3VGLL1psi-mi:“MI:0915”(physical association)0.560
VGLL1AIRIMpsi-mi:“MI:0915”(physical association)0.560
MEIS2VGLL1psi-mi:“MI:0915”(physical association)0.560
LONRF1VGLL1psi-mi:“MI:0915”(physical association)0.560
CDKN2DVGLL1psi-mi:“MI:0915”(physical association)0.560
TEKT4VGLL1psi-mi:“MI:0915”(physical association)0.560
RIPPLY1VGLL1psi-mi:“MI:0915”(physical association)0.560
TEAD2VGLL1psi-mi:“MI:0915”(physical association)0.560
TLE5VGLL1psi-mi:“MI:0915”(physical association)0.560
TEAD2VGLL1psi-mi:“MI:0915”(physical association)0.000
VGLL1TEAD3psi-mi:“MI:0915”(physical association)0.000
TEAD4VGLL1psi-mi:“MI:0915”(physical association)0.000
HNRNPFVGLL1psi-mi:“MI:0915”(physical association)0.000
PFDN5VGLL1psi-mi:“MI:0915”(physical association)0.000
TRIM23VGLL1psi-mi:“MI:0915”(physical association)0.000
TSSK3VGLL1psi-mi:“MI:0915”(physical association)0.000
AIRIMVGLL1psi-mi:“MI:0915”(physical association)0.000
MEIS2VGLL1psi-mi:“MI:0915”(physical association)0.000
LONRF1VGLL1psi-mi:“MI:0915”(physical association)0.000
CDKN2DVGLL1psi-mi:“MI:0915”(physical association)0.000
TEKT4VGLL1psi-mi:“MI:0915”(physical association)0.000

BioGRID (20): VGLL1 (Two-hybrid), VGLL1 (Two-hybrid), AES (Two-hybrid), TRIM23 (Two-hybrid), C1orf109 (Two-hybrid), PFDN5 (Two-hybrid), CDKN2D (Two-hybrid), MEIS2 (Two-hybrid), RIPPLY1 (Two-hybrid), LONRF1 (Two-hybrid), TSSK3 (Two-hybrid), TEKT4 (Two-hybrid), HNRNPF (Two-hybrid), TEAD4 (Two-hybrid), TEAD2 (Two-hybrid)

ESM2 similar proteins: A0PJS5, A3KNX5, A8K830, F8VPY8, O54968, P01102, P01105, P12979, P15173, P28322, P41161, P41164, P43268, P49812, P50549, P53450, Q14140, Q16633, Q29RM2, Q2KIC2, Q2KJA4, Q4G112, Q56TN0, Q56TT7, Q5M7N6, Q5M9G5, Q5R815, Q5ZKN5, Q60795, Q64693, Q66IT9, Q6NYT3, Q6PB51, Q6PBC9, Q7YR76, Q7YS81, Q80V38, Q80VF6, Q8BGR5, Q8BXQ8

Diamond homologs: A8MV65, P85442, Q26366, Q8BGW8, Q8N8G2, Q99990, Q99NC0

SIGNOR signaling

1 interactions.

AEffectBMechanism
RPS6KA3“down-regulates activity”VGLL1phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

58 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance28
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

706 predictions. Top by Δscore:

VariantEffectΔscore
X:136550822:G:GGdonor_gain1.0000
X:136532293:AGAG:Adonor_loss0.9900
X:136532294:GAG:Gdonor_gain0.9900
X:136532296:GGTA:Gdonor_loss0.9900
X:136532297:G:Tdonor_loss0.9900
X:136532298:T:Gdonor_loss0.9900
X:136535994:A:AGacceptor_gain0.9900
X:136535995:G:GGacceptor_gain0.9900
X:136535995:GC:Gacceptor_gain0.9900
X:136535995:GCT:Gacceptor_gain0.9900
X:136536189:G:GTdonor_gain0.9900
X:136536235:GTG:Gdonor_loss0.9900
X:136536236:T:Adonor_loss0.9900
X:136536237:G:GTdonor_loss0.9900
X:136548964:G:GTdonor_gain0.9900
X:136550766:A:AGacceptor_gain0.9900
X:136550767:G:GGacceptor_gain0.9900
X:136550767:GATAA:Gacceptor_gain0.9900
X:136550818:GAAA:Gdonor_gain0.9900
X:136535991:CACA:Cacceptor_loss0.9800
X:136535992:ACAG:Aacceptor_loss0.9800
X:136535993:CA:Cacceptor_loss0.9800
X:136535994:A:Cacceptor_loss0.9800
X:136535994:AGCT:Aacceptor_gain0.9800
X:136535995:GCTG:Gacceptor_gain0.9800
X:136535995:GCTGT:Gacceptor_gain0.9800
X:136536020:A:AGacceptor_gain0.9800
X:136536214:AAGGT:Adonor_gain0.9800
X:136536238:AG:Adonor_loss0.9800
X:136549009:G:GGdonor_gain0.9800

AlphaMissense

1676 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
X:136536153:T:CF45L0.999
X:136536154:T:CF45S0.999
X:136536155:C:AF45L0.999
X:136536155:C:GF45L0.999
X:136536154:T:GF45C0.997
X:136536109:T:CF30S0.996
X:136536117:T:CF33L0.996
X:136536119:C:AF33L0.996
X:136536119:C:GF33L0.996
X:136536145:A:TD42V0.995
X:136536152:C:AH44Q0.995
X:136536152:C:GH44Q0.995
X:136536161:A:CR47S0.995
X:136536161:A:TR47S0.995
X:136536114:T:GY32D0.994
X:136536118:T:CF33S0.993
X:136536163:C:AA48D0.993
X:136536103:T:AV28D0.992
X:136536123:G:AG35R0.992
X:136536123:G:CG35R0.992
X:136536144:G:CD42H0.992
X:136536150:C:GH44D0.992
X:136536151:A:GH44R0.992
X:136536166:T:CL49P0.992
X:136536145:A:CD42A0.991
X:136536151:A:CH44P0.991
X:136536160:G:CR47T0.991
X:136536162:G:CA48P0.991
X:136536156:T:CS46P0.990
X:136536160:G:TR47I0.990

dbSNP variants (sampled 300 via entrez): RS1000046111 (X:136538282 C>T), RS1000053115 (X:136537621 G>A), RS1000112802 (X:136540329 G>A,T), RS1000280948 (X:136545027 A>C), RS1000474240 (X:136537330 A>C,G), RS1000708861 (X:136556058 G>A), RS1000709082 (X:136543730 A>C), RS1000723989 (X:136547860 A>G), RS1000771787 (X:136531329 T>C), RS1000776605 (X:136555454 CT>C,CTT), RS1000818940 (X:136557051 C>T), RS1000886524 (X:136547162 G>A), RS1000932996 (X:136556659 A>G), RS1000972686 (X:136530791 A>C), RS1000984272 (X:136546066 C>A)

Disease associations

OMIM: gene MIM:300583 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, decreases expression, decreases methylation6
trichostatin Aaffects cotreatment, increases expression3
Benzo(a)pyreneaffects methylation, increases expression, increases methylation3
mercuric bromideincreases expression, affects cotreatment2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression2
Vorinostataffects cotreatment, increases expression2
Panobinostataffects cotreatment, increases expression2
Air Pollutantsdecreases expression, increases abundance2
Ethinyl Estradiolaffects expression, decreases expression2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Smokeincreases abundance, decreases expression2
p-Chloromercuribenzoic Acidaffects cotreatment, increases expression2
bisphenol Aaffects expression1
ascorbate-2-phosphateaffects cotreatment, increases expression, affects binding1
3,4-dichloroanilinedecreases expression1
sodium arsenitedecreases expression1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acidaffects cotreatment, increases expression1
cylindrospermopsinincreases expression1
corosolic acidincreases expression1
2-palmitoylglycerolincreases expression1
Chir 99021affects binding, affects cotreatment, increases expression1
dorsomorphinaffects cotreatment, increases expression1
XAV939affects binding, affects cotreatment, increases expression1
LDN 193189affects cotreatment, increases expression1
(+)-JQ1 compounddecreases expression1
3-(4-pyridyl)-1H-indoleaffects cotreatment, increases expression1
Resveratrolaffects cotreatment, decreases expression1
Amphotericin Bincreases expression1
Ascorbic Acidaffects binding, affects cotreatment, increases expression1
Diethylhexyl Phthalateincreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot