TEAD4

gene
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Also known as TEF-3TEFR-1EFTR-2RTEF-1

Summary

TEAD4 (TEA domain transcription factor 4, HGNC:11717) is a protein-coding gene on chromosome 12p13.33, encoding Transcriptional enhancer factor TEF-3 (Q15561). Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.

This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNA-binding domain. It is preferentially expressed in the skeletal muscle, and binds to the M-CAT regulatory element found in promoters of muscle-specific genes to direct their gene expression. Alternatively spliced transcripts encoding distinct isoforms, some of which are translated through the use of a non-AUG (UUG) initiation codon, have been described for this gene.

Source: NCBI Gene 7004 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 82 total
  • Druggable target: yes — 3 molecules with ChEMBL bioactivity
  • Transcription factor: yes — 14 downstream targets (CollecTRI)
  • MANE Select transcript: NM_003213

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11717
Approved symbolTEAD4
NameTEA domain transcription factor 4
Location12p13.33
Locus typegene with protein product
StatusApproved
AliasesTEF-3, TEFR-1, EFTR-2, RTEF-1
Ensembl geneENSG00000197905
Ensembl biotypeprotein_coding
OMIM601714
Entrez7004

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000358409, ENST00000359864, ENST00000397122, ENST00000443986, ENST00000536826, ENST00000540314, ENST00000543035, ENST00000544666

RefSeq mRNA: 3 — MANE Select: NM_003213 NM_003213, NM_201441, NM_201443

CCDS: CCDS31729, CCDS31730, CCDS41737

Canonical transcript exons

ENST00000359864 — 13 exons

ExonStartEnd
ENSE0000127606930401073040259
ENSE0000127607730379683038108
ENSE0000127608430218443022017
ENSE0000127609030206343020773
ENSE0000136926129599482960040
ENSE0000179616029593972959481
ENSE0000222463029947382994992
ENSE0000227093730403653040676
ENSE0000349463430173983017526
ENSE0000358994630110043011068
ENSE0000360157030191153019170
ENSE0000365388530121703012232
ENSE0000378514430185453018588

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 96.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.4142 / max 250.6254, expressed in 1534 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter IDTPM avgSamples expressed
12346210.06211428
1234693.48931241
1234602.18191011
1234611.6306835
1234630.4734238
1234670.4030216
1234640.3471172
1234590.3231152
1234680.2518117
1234660.107834

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
hindlimb stylopod muscleUBERON:000425296.21gold quality
gastrocnemiusUBERON:000138896.03gold quality
muscle of legUBERON:000138394.86gold quality
muscle organUBERON:000163094.22gold quality
gluteal muscleUBERON:000200093.57gold quality
triceps brachiiUBERON:000150993.37gold quality
tibialis anteriorUBERON:000138592.82gold quality
quadriceps femorisUBERON:000137792.58gold quality
skeletal muscle tissueUBERON:000113492.52gold quality
vastus lateralisUBERON:000137992.35gold quality
body of pancreasUBERON:000115091.81gold quality
biceps brachiiUBERON:000150791.47gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099191.20gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450290.24gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451190.19gold quality
muscle tissueUBERON:000238590.01gold quality
diaphragmUBERON:000110389.94gold quality
deltoidUBERON:000147689.08gold quality
right lobe of thyroid glandUBERON:000111988.35gold quality
right lungUBERON:000216788.21gold quality
left lobe of thyroid glandUBERON:000112087.80gold quality
upper lobe of left lungUBERON:000895287.79gold quality
upper lobe of lungUBERON:000894887.19gold quality
cartilage tissueUBERON:000241887.17gold quality
pancreasUBERON:000126486.92gold quality
thyroid glandUBERON:000204686.59gold quality
tendon of biceps brachiiUBERON:000818886.21gold quality
endometrium epitheliumUBERON:000481185.35gold quality
sural nerveUBERON:001548884.51gold quality
apex of heartUBERON:000209883.94gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes9.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

TargetRegulation
ACTA1
ADAM2
CCN2Unknown
CDX2Unknown
EIF3K
FGFR1Activation
HIF1AActivation
IGFBP1Activation
MYH7Activation
PPP1CBActivation
S100BRepression
S1PR1Activation
VEGFARepression
VEGFBUnknown

JASPAR motifs

MotifNameFamily
MA0809.1TEAD4TEF-1-related factors
MA0809.2TEAD4TEF-1-related factors
MA0809.3TEAD4TEF-1-related factors

JASPAR matrix evidence (PMIDs): PMID:9571041, PMID:23332764

miRNA regulators (miRDB)

13 targeting TEAD4, 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-6783-3P99.8967.922059
HSA-MIR-1343-3P99.8966.781815
HSA-MIR-4766-5P99.7569.232662
HSA-MIR-6887-3P99.6667.831778
HSA-MIR-6715B-5P99.6469.631420
HSA-MIR-426999.5569.891373
HSA-MIR-6839-3P99.3968.861301
HSA-MIR-3940-5P99.1465.26493
HSA-MIR-450799.1465.27515
HSA-MIR-146A-3P99.1368.991881
HSA-MIR-3074-5P98.8266.561414
HSA-MIR-629-5P98.7868.721032
HSA-MIR-6742-3P97.9564.501490

Literature-anchored findings (GeneRIF, showing 40)

  • Constitutive activation of alpha1-adrenergic signaling through the RTEF-1 transcription factor results in chronic elevation of PP1beta expression and connexin dephosphorylation. This mechanism may underlie some defects in cardiac conduction. (PMID:15520314)
  • Novel RTEF-1 transcripts are present within human ocular vascular endothelial cells and mouse neural retina during normal and retinopathy of prematurity development, and alternatively spliced products are produced under hyperoxic and hypoxic conditions (PMID:17652751)
  • The gain of function studies indicated that TEA domain family member 4 activate NR5A1 gene expression. (PMID:18579725)
  • TEF3 mediates the expression of Down syndrome candidate region 1 isoform 1 (DSCR1-1L) in endothelial cells (PMID:18840614)
  • the RTEF-1-driven increase of VEGF-B plays an important role in communication between the endothelium and myocardium (PMID:21169295)
  • TEF3, mainly its nuclear localization, is required for VEGF-A(165)-induced endothelial proliferation, migration, tube formation, and in vivo Matrigel angiogenesis. (PMID:21169383)
  • RTEF-1 as a regulator of HIF-1alpha transcription (PMID:21540178)
  • RTEF-1 plays an important role in FGFR1- stimulated vasodilatation. (PMID:22433836)
  • Blocking connexin 43 function inhibited RTEF-1-induced endothelial cell connections and aggregation (PMID:22652601)
  • High TEAD4 expression is associated with Age-Related Macular Degeneration. (PMID:22761647)
  • These results show that RTEF-1-stimulated IGFBP-1 expression may be central to the mechanism by which RTEF-1 attenuates blood glucose levels. (PMID:22843786)
  • These data suggest that TFF3 and survivin expressions play a vital role in gastric cancer development, and these two proteins are important markers for prognosis in gastric cancer. (PMID:22996285)
  • Data indicate that knockdown of TEAD1/3/4 induces an almost identical cellular senescent phenotype as YAP silencing. (PMID:23576552)
  • convergent optimization of the YAP/TAZ TEAD binding site suggests that the similarity in the affinities of binding of YAP to TEAD and of TAZ to TEAD is important for Hippo pathway functionality. (PMID:23780915)
  • the multilevel perturbations of TEAD4 at epigenetic, transcriptional and posttranslational levels may contribute to GC development. (PMID:24325916)
  • Edg-1 is a potential target gene of RTEF-1 and is involved in RTEF-1-induced angiogenesis in endothelial cells. (PMID:24520353)
  • Our findings suggest that genetic variants of Hippo pathway genes, particularly YAP1 rs11225163, TEAD1 rs7944031 and TEAD4 rs1990330, may independently or jointly modulate survival of CM patients. (PMID:25628125)
  • the peptides TEF3-11-66 and TEF3-1197-434 functioned as two independent activation domains, suggesting that N-terminal domain of TEF3-1 also has transcriptional activation capacity (PMID:25687649)
  • TEAD4 and KLF5, in collaboration, promoted triple negative breast cancer cell proliferation and tumor growth in part by inhibiting p27 gene transcription (PMID:25970772)
  • TAZ negatively regulate transcription of DeltaNp63 through TEAD1,2,3 and 4 transcription factors. (PMID:25995450)
  • potential anti-oxidation gene and can prevent H2O2-induced endothelial cell oxidative damage by activating Klotho (PMID:26041389)
  • The transcription factor TEAD4 regulates a pro-metastasis transcription program in a YAP-independent manner in CRC, thus providing a novel mechanism of TEAD4 transcriptional regulation and its oncogenic role in CRC, independently of the Hippo pathway. (PMID:26387538)
  • TEAD4 overexpression induced p16 in HAoSMCs homozygous for the nonrisk coronary disease allele, but not for the risk allele. (PMID:26487755)
  • Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. (PMID:26832411)
  • High TEF3 expression is associated with cell cycle progression and angiogenesis in colon cancer. (PMID:26885617)
  • TEAD4, the transcription factor that mediates Hippo-YAP signalling, undergoes alternative splicing facilitated by the tumour suppressor RBM4. (PMID:27291620)
  • Our results suggest that TEAD4 plays a role in the pathophysiology of atypical teratoid/rhabdoid tumor, which represents a new insight into the biology of this aggressive tumor (PMID:27966820)
  • Hippo pathway transcription factor TEAD4 directly associates with the Wnt pathway transcription factor TCF4 via their DNA-binding domains, forming a complex on target genes. VGLL4 binds to this TEAD4-TCF4 complex to inhibit transactivation of both TCF4 and TEAD4. (PMID:28051067)
  • Collectively, these results indicate that human papillomavirus 16 E6 induces upregulation of APOBEC3B through increased levels of TEADs, highlighting the importance of the TEAD-APOBEC3B axis in carcinogenesis. (PMID:28077648)
  • It was found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. (PMID:28315328)
  • our work provides a structural basis for understanding the regulatory mechanism of TEAD4-mediated gene transcription (PMID:28368398)
  • Combining single site-directed mutagenesis and double mutant analyses, the authors conduct a detailed analysis on the role of several residues located at the YAP:TEAD interface. The results provide quantitative understanding of the interactions taking place at the YAP:TEAD interface and give insights into the formation of the YAP:TEAD complex and more particularly on the interaction between TEAD and the ohm-loop found … (PMID:28430104)
  • Osmotic stress promotes TEAD4 cytoplasmic translocation via p38 MAPK in a Hippo-independent manner. Stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth. (PMID:28752853)
  • TEAD1 and TEAD4 are oncogenic factors, whose aberrant activation are, in part, mediated by the silence of miR-377-3p, miR-1343-3p and miR-4269. (PMID:28759040)
  • Studied the effect of TEAD4 acylation on its interaction with YAP and TAZ; found YAP and TAZ bind in a similar manner to both acylated and non-acylated TEAD4. Also found TEAD4 acylation significantly enhances its stability. (PMID:28960584)
  • TEAD4 plays an important tumor-promoting role in colorectal cancer by directly targeting the YAP1. (PMID:29157094)
  • TEAD4 is up-regulated in lung adenocarcinoma and its expression is an unfavourable prognostic factor.TEAD4 expression is regulated by miR-6839-3p. (PMID:29667772)
  • LOX nuclear localization was significantly associated with poor survival in patients with Colorectal cancer (CRC). Nuclear LOX expression was correlated with synchronous or postoperative lung/hepatic metastasis. LOX may prove to be a potential target gene of YAP and TEAD4. (PMID:29766649)
  • To analyze the clinical characteristics, treatment methods and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (PMID:30392265)
  • High TEAD4 expression is associated with Hepatoblastoma. (PMID:30794805)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
mus_musculusTead4ENSMUSG00000030353
rattus_norvegicusTead4ENSRNOG00000005608
drosophila_melanogastersdFBGN0003345

Paralogs (3): TEAD3 (ENSG00000007866), TEAD2 (ENSG00000074219), TEAD1 (ENSG00000187079)

Protein

Protein identifiers

Transcriptional enhancer factor TEF-3Q15561 (reviewed: Q15561)

Alternative names: TEA domain family member 4, Transcription factor 13-like 1, Transcription factor RTEF-1

All UniProt accessions (8): A0A0A0MRF3, Q15561, H0Y7B0, H0YFF9, H0YFK0, H0YG62, H0YGS2, Q53GI4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC ’enhansons’ (5’-GTGGAATGT-3’) and activates transcription. Binds to the M-CAT motif.

Subunit / interactions. Interacts with YAP1 and WWTR1/TAZ.

Subcellular location. Nucleus.

Tissue specificity. Preferentially expressed in skeletal muscle. Lower levels in pancreas, placenta, and heart.

Isoforms (3)

UniProt IDNamesCanonical?
Q15561-11yes
Q15561-22
Q15561-33

RefSeq proteins (3): NP_003204, NP_958849, NP_958851 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000818TEA/ATTS_domDomain
IPR016361TEF_metazoaFamily
IPR027255TEF-3Family
IPR038096TEA/ATTS_sfHomologous_superfamily
IPR041086YBDDomain
IPR050937

Pfam: PF01285, PF17725

UniProt features (54 total): strand 16, helix 12, mutagenesis site 11, sequence conflict 5, region of interest 2, compositionally biased region 2, splice variant 2, chain 1, DNA-binding region 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

23 structures.

PDBMethodResolution (Å)
9SYNX-RAY DIFFRACTION1.3
6GEIX-RAY DIFFRACTION1.65
6HIKX-RAY DIFFRACTION1.65
6SENX-RAY DIFFRACTION1.65
8A8RX-RAY DIFFRACTION1.7
6GECX-RAY DIFFRACTION1.7
9QKQX-RAY DIFFRACTION1.74
6GE6X-RAY DIFFRACTION1.8
6GE3X-RAY DIFFRACTION1.85
5OAQX-RAY DIFFRACTION1.95
6GEEX-RAY DIFFRACTION1.96
6GE4X-RAY DIFFRACTION1.97
8CAAX-RAY DIFFRACTION2
6Q36X-RAY DIFFRACTION2.01
6GE5X-RAY DIFFRACTION2.05
6Q2XX-RAY DIFFRACTION2.1
9SYIX-RAY DIFFRACTION2.1
6GEGX-RAY DIFFRACTION2.23
8C17X-RAY DIFFRACTION2.25
6GEKX-RAY DIFFRACTION2.28
6SEOX-RAY DIFFRACTION2.55
5GZBX-RAY DIFFRACTION2.7
5NO6X-RAY DIFFRACTION2.88

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q15561-F176.750.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (11):

PositionPhenotype
297important loss of interaction with yap1 and complete loss of transforming ability.
299important loss of interaction with yap1 and complete loss of transforming ability.
337reduced interaction with yap1.
373reduced transforming ability.
380reduced transforming ability.
391reduced transforming ability.
393reduced transforming ability.
427reduced transforming ability.
429loss of interaction with yap1 and also activation by yap1.
429important loss of interaction with yap1 and complete loss of transforming ability.
266reduced transforming ability.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

IDPathway
R-HSA-2032785YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-8951671RUNX3 regulates YAP1-mediated transcription
R-HSA-9796292Formation of axial mesoderm
R-HSA-9819196Zygotic genome activation (ZGA)
R-HSA-9909649Regulation of PD-L1(CD274) transcription
R-HSA-1266738Developmental Biology
R-HSA-212436Generic Transcription Pathway
R-HSA-73857RNA Polymerase II Transcription
R-HSA-74160Gene expression (Transcription)
R-HSA-8878159Transcriptional regulation by RUNX3
R-HSA-9758941Gastrulation
R-HSA-9816359Maternal to zygotic transition (MZT)

MSigDB gene sets: 171 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MYOGENIN_Q6, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_HIPPO_SIGNALING, GOBP_BLASTOCYST_FORMATION, WEI_MYCN_TARGETS_WITH_E_BOX, DAUER_STAT3_TARGETS_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, WOO_LIVER_CANCER_RECURRENCE_UP, KORKOLA_EMBRYONAL_CARCINOMA_UP, BILD_E2F3_ONCOGENIC_SIGNATURE

GO Biological Process (16): skeletal system development (GO:0001501), cell fate specification (GO:0001708), trophectodermal cell fate commitment (GO:0001830), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), muscle organ development (GO:0007517), embryo implantation (GO:0007566), hippo signaling (GO:0035329), embryonic organ development (GO:0048568), positive regulation of stem cell population maintenance (GO:1902459), in utero embryonic development (GO:0001701), blastocyst formation (GO:0001825), regulation of DNA-templated transcription (GO:0006355), cell fate commitment (GO:0045165), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-8 pathways:

CategoryPathways
Generic Transcription Pathway2
Developmental Biology2
Transcriptional regulation by RUNX31
Gastrulation1
Maternal to zygotic transition (MZT)1
Regulation of PD-L1(CD274) expression1
RNA Polymerase II Transcription1
Gene expression (Transcription)1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of DNA-templated transcription3
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
cellular anatomical structure3
cell fate commitment2
cellular developmental process2
transcription by RNA polymerase II2
animal organ development2
DNA-templated transcription2
regulation of transcription by RNA polymerase II2
protein-containing complex2
system development1
trophectodermal cell differentiation1
gene expression1
RNA biosynthetic process1
muscle structure development1
multicellular organism development1
female pregnancy1
reproductive process1
intracellular signal transduction1
embryo development1
stem cell population maintenance1
positive regulation of developmental process1
positive regulation of multicellular organismal process1
regulation of stem cell population maintenance1
chordate embryonic development1
blastocyst development1
anatomical structure formation involved in morphogenesis1
regulation of gene expression1
regulation of RNA biosynthetic process1
cell differentiation1
positive regulation of RNA biosynthetic process1
positive regulation of DNA-templated transcription1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1
DNA-binding transcription factor activity, RNA polymerase II-specific1
DNA-binding transcription activator activity1
positive regulation of transcription by RNA polymerase II1
transcription cis-regulatory region binding1
transcription regulator activity1

Protein interactions and networks

STRING

2086 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TEAD4YAP1P46937992
TEAD4MCATQ8IVS2885
TEAD4VGLL4Q14135881
TEAD4VGLL1Q99990879
TEAD4EP300Q09472844
TEAD4SMAD3P84022802
TEAD4CDX2Q99626799
TEAD4WWTR1Q9GZV5786
TEAD4ELF5Q9UKW6734
TEAD4GATA3P23771709
TEAD4LATS1O95835708
TEAD4POU5F1P31359705
TEAD4EOMESO95936663
TEAD4VGLL3A8MV65660
TEAD4LATS2Q9NRM7650

IntAct

181 interactions, top by confidence:

ABTypeScore
YAP1TEAD4psi-mi:“MI:0915”(physical association)0.930
TEAD4YAP1psi-mi:“MI:0407”(direct interaction)0.930
TEAD4YAP1psi-mi:“MI:0914”(association)0.930
YAP1TEAD4psi-mi:“MI:0407”(direct interaction)0.930
TEAD4WWTR1psi-mi:“MI:0915”(physical association)0.920
VGLL4TEAD4psi-mi:“MI:0407”(direct interaction)0.760
TEAD4VGLL4psi-mi:“MI:0915”(physical association)0.760
TEAD4CEP55psi-mi:“MI:0915”(physical association)0.740
TEAD4TRIM27psi-mi:“MI:0915”(physical association)0.720
TEAD4TRAF1psi-mi:“MI:0915”(physical association)0.720
TEAD4KRT40psi-mi:“MI:0915”(physical association)0.720
TEAD4GOLGA2psi-mi:“MI:0915”(physical association)0.720
TEAD4MTUS2psi-mi:“MI:0915”(physical association)0.720

BioGRID (165): TEAD4 (Two-hybrid), TEAD4 (Two-hybrid), TEAD4 (Two-hybrid), TRAF1 (Two-hybrid), PNMA1 (Two-hybrid), KIAA0753 (Two-hybrid), CCNDBP1 (Two-hybrid), RABGEF1 (Two-hybrid), CEP55 (Two-hybrid), CEP70 (Two-hybrid), LZTS2 (Two-hybrid), SSX2IP (Two-hybrid), CCDC172 (Two-hybrid), TEAD4 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS)

ESM2 similar proteins: B5DF93, D2HNW6, O14896, P52633, P56477, P70671, P97431, Q08DD6, Q13568, Q14653, Q15561, Q15562, Q1JPG0, Q3B7M3, Q3TC46, Q3ZBK7, Q4JF28, Q4KLN4, Q53GS7, Q58DJ0, Q5DTY9, Q5R8Q4, Q5RAS2, Q62717, Q68DU8, Q6A0A9, Q6DEZ2, Q6NUQ4, Q7L4E1, Q86TB9, Q86UW7, Q86UW9, Q8AVJ1, Q8BK03, Q8BYR5, Q8CDG3, Q8CF97, Q8CID0, Q8HWS3, Q8IY22

Diamond homologs: A0A0A7HMS2, B6H7F3, C0STD9, E9EMI7, E9RD40, I1S4T3, K9GDC6, P18412, P20945, P28347, P30051, P30052, P48301, P48984, P70210, Q15561, Q15562, Q19849, Q2U9L6, Q5ANJ4, Q62296, Q90701, Q99594, W6PQG8, Q25214

SIGNOR signaling

4 interactions.

AEffectBMechanism
WWTR1up-regulatesTEAD4binding
YAP1up-regulatesTEAD4binding
YAP1“up-regulates activity”TEAD4binding
TEAD4“up-regulates quantity by expression”CCN2“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance65
Likely benign4
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3139 predictions. Top by Δscore:

VariantEffectΔscore
12:2994988:GTATG:Gdonor_gain1.0000
12:2994990:ATGGT:Adonor_loss1.0000
12:2994991:TGGT:Tdonor_loss1.0000
12:2994992:GGT:Gdonor_loss1.0000
12:2994993:GT:Gdonor_loss1.0000
12:2994994:T:Adonor_loss1.0000
12:3011062:G:GTdonor_gain1.0000
12:3012229:AAAGG:Adonor_loss1.0000
12:3012231:AGGTA:Adonor_loss1.0000
12:3012234:T:Adonor_loss1.0000
12:3014410:G:Tdonor_gain1.0000
12:3017523:AGGGG:Adonor_loss1.0000
12:3017524:GGG:Gdonor_gain1.0000
12:3017525:GGG:Gdonor_gain1.0000
12:3017527:GTAA:Gdonor_loss1.0000
12:3017528:T:TCdonor_loss1.0000
12:3018543:A:AGacceptor_gain1.0000
12:3018544:G:GGacceptor_gain1.0000
12:3018544:GTTTT:Gacceptor_gain1.0000
12:3018587:GA:Gdonor_gain1.0000
12:3018589:G:GGdonor_gain1.0000
12:3019113:A:AGacceptor_gain1.0000
12:3019114:G:GGacceptor_gain1.0000
12:3020632:AG:Aacceptor_gain1.0000
12:3020633:GG:Gacceptor_gain1.0000
12:3020633:GGGTT:Gacceptor_gain1.0000
12:3020772:CGG:Cdonor_loss1.0000
12:3020774:G:GGdonor_gain1.0000
12:3020775:T:Gdonor_loss1.0000
12:3021826:GACCC:Gacceptor_gain1.0000

AlphaMissense

2871 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:2994893:T:AW43R1.000
12:2994893:T:CW43R1.000
12:2994894:G:CW43S1.000
12:2994895:G:CW43C1.000
12:2994895:G:TW43C1.000
12:2994917:T:CF51L1.000
12:2994918:T:CF51S1.000
12:2994918:T:GF51C1.000
12:2994919:C:AF51L1.000
12:2994919:C:GF51L1.000
12:2994926:G:CA54P1.000
12:2994927:C:AA54D1.000
12:2994930:T:CL55P1.000
12:2994938:T:CY58H1.000
12:2994938:T:GY58D1.000
12:2994947:T:CC61R1.000
12:2994948:G:AC61Y1.000
12:2994949:T:GC61W1.000
12:2994950:G:CG62R1.000
12:2994950:G:TG62C1.000
12:2994951:G:AG62D1.000
12:2994951:G:TG62V1.000
12:2994953:A:GR63G1.000
12:2994953:A:TR63W1.000
12:2994954:G:CR63T1.000
12:2994954:G:TR63M1.000
12:2994955:G:CR63S1.000
12:2994955:G:TR63S1.000
12:2994956:C:AR64S1.000
12:2994956:C:TR64C1.000

dbSNP variants (sampled 300 via entrez): RS1000012605 (12:2999293 C>G,T), RS1000128262 (12:3039217 A>G), RS1000140991 (12:2969344 G>A,T), RS1000142410 (12:3026988 C>T), RS1000148523 (12:2974056 G>A,C), RS1000175200 (12:2957552 C>G,T), RS1000177089 (12:3027193 A>G), RS1000190431 (12:3013297 C>G,T), RS1000205431 (12:2993842 C>A,T), RS1000232996 (12:2988393 C>T), RS1000274526 (12:2968232 A>G,T), RS1000286702 (12:2988669 A>G), RS1000287189 (12:3021606 C>T), RS1000313874 (12:3004237 G>A), RS1000410583 (12:3016162 G>T)

Disease associations

OMIM: gene MIM:601714 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST001909_3Narcolepsy with cataplexy2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL4295828 (SINGLE PROTEIN), CHEMBL5465250 (PROTEIN COMPLEX), CHEMBL6066038 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193819 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195574 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 51,894 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL23588FLUFENAMIC ACID234,797
CHEMBL32350PIRLINDOLE21,928
CHEMBL63323NIFLUMIC ACID215,169

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — TEAD (transcriptional enhanced associate domain) transcription factors

Most potent curated ligand interactions (1 total), top 1:

LigandActionAffinityParameter
GNE-7883Binding7.52pIC50

Binding affinities (BindingDB)

104 measured of 110 human assays (110 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
US12083101, Example 71bIC501 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 110IC501 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 112IC501 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 147IC501 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 170IC501 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 12IC501.5 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 38IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 56bIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 66aIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 66bIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 67aIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 71aIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 94aIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 99IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 100aIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 104bIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 108IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 113IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 115aIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 115bIC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 121IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 126IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 151IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 152IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 171IC502 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 31IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 33IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 51IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 57bIC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 86IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 94bIC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 102aIC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 120IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 143IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 146IC503 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 8IC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 58bIC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 69bIC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 85aIC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 97IC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 111IC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 140aIC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 150IC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 164IC504 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 49IC505 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 69aIC505 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 96IC505 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 98IC505 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 103IC505 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 141IC505 nMUS-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors

ChEMBL bioactivities

121 potent at pChembl≥5 of 177 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.80Ki1.6nMCHEMBL6147038
8.70IC502nMCHEMBL5401444
8.70IC502nMCHEMBL5422959
8.70IC502nMCHEMBL5400400
8.70IC502nMCHEMBL5408536
8.70IC502nMCHEMBL5403826
8.52IC503nMCHEMBL5419829
8.52IC503nMCHEMBL5416415
8.52IC503nMCHEMBL5415215
8.52IC503nMCHEMBL5438256
8.52IC503nMCHEMBL5432828
8.52IC503nMCHEMBL5428867
8.05IC509nMCHEMBL4567546
8.05IC509nMCHEMBL5411200
7.83Ki14.9nMCHEMBL6142714
7.80IC5016nMCHEMBL4468725
7.60Kd25nMCHEMBL4468725
7.35IC5045nMCHEMBL4467555
7.25IC5056nMCHEMBL4476332
7.16IC5070nMCHEMBL242708
7.00IC50100nMCHEMBL4787565
6.71IC50197nMCHEMBL4459587
6.70IC50200nMCHEMBL4776143
6.70IC50200nMCHEMBL4757924
6.70IC50200nMCHEMBL4745853
6.70IC50200nMCHEMBL4757369
6.70IC50200nMCHEMBL4745831
6.70IC50200nMCHEMBL242708
6.70IC50200nMCHEMBL5405832
6.67IC50216nMCHEMBL4514336
6.52IC50300nMCHEMBL1701986
6.52IC50300nMCHEMBL4789889
6.52IC50300nMCHEMBL4797833
6.52IC50300nMCHEMBL4750726
6.52IC50300nMCHEMBL4783341
6.52IC50300nMCHEMBL4744235
6.52IC50300nMCHEMBL5405832
6.40IC50400nMCHEMBL4800702
6.40IC50400nMCHEMBL4750624
6.40IC50400nMCHEMBL5424157
6.39IC50409nMCHEMBL4436894
6.39IC50410nMCHEMBL5436703
6.30IC50500nMCHEMBL4757939
6.29IC50510nMCHEMBL5220985
6.22IC50600nMCHEMBL5432067
6.17IC50672nMCHEMBL5397201
6.16IC50700nMCHEMBL4787565
6.16IC50700nMCHEMBL5432067
6.10IC50800nMCHEMBL4763473
6.05IC50900nMCHEMBL4784286

PubChem BioAssay actives

122 with measured affinity, of 591 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-[(2S,3S)-5-chloro-6-fluoro-3-methyl-2-(methylaminomethyl)-2-phenyl-3H-1-benzofuran-4-yl]-3-fluoro-4-methoxybenzamide2007263: Inhibition of Avi-His-tagged human TEAD4 (217 to 434 residues)/N-biotinylated-N-terminal Cy5-labelled human YAP (60 to 100 residues) incubated for 1 hr by TR FRET assayic500.0020uM
2-[(2S,3S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-3H-1-benzofuran-4-yl]-3-fluoro-4-(2-methoxyethoxy)benzamide2007263: Inhibition of Avi-His-tagged human TEAD4 (217 to 434 residues)/N-biotinylated-N-terminal Cy5-labelled human YAP (60 to 100 residues) incubated for 1 hr by TR FRET assayic500.0020uM
N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]methyl]prop-2-ynamide2020151: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assayic500.0020uM
2-chloro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]methyl]prop-2-enamide2020151: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assayic500.0020uM
cyclobuten-1-yl-[3-[9-methyl-6-[4-(trifluoromethoxy)phenyl]purin-2-yl]azetidin-1-yl]methanone2015512: Displacement of biotinylated lipid pocket probes from His-tagged TEAD4 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assayic500.0020uM
1-[3-[7-[4-(trifluoromethoxy)phenyl]-[1,3]thiazolo[5,4-d]pyrimidin-5-yl]azetidin-1-yl]prop-2-en-1-one2015512: Displacement of biotinylated lipid pocket probes from His-tagged TEAD4 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assayic500.0020uM
1-[3-[9-methyl-6-[4-(trifluoromethoxy)phenyl]purin-2-yl]azetidin-1-yl]prop-2-en-1-one2015512: Displacement of biotinylated lipid pocket probes from His-tagged TEAD4 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assayic500.0020uM
2-[(2S,3R)-2-(aminomethyl)-5-chloro-6-fluoro-3-(hydroxymethyl)-2-phenyl-3H-1-benzofuran-4-yl]-3-fluoro-4-methoxybenzamide2007263: Inhibition of Avi-His-tagged human TEAD4 (217 to 434 residues)/N-biotinylated-N-terminal Cy5-labelled human YAP (60 to 100 residues) incubated for 1 hr by TR FRET assayic500.0020uM
2-chloro-N-methyl-N-[[1-[4-(trifluoromethoxy)phenyl]indazol-3-yl]methyl]acetamide2020151: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assayic500.0030uM
(E)-1-[3-[4-chloro-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]-4-hydroxybut-2-en-1-one2020151: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assayic500.0030uM
1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one2020151: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assayic500.0030uM
N-[[4-(hydroxymethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1-benzofuran-5-yl]methyl]ethenesulfonamide2015512: Displacement of biotinylated lipid pocket probes from His-tagged TEAD4 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assayic500.0030uM
N-[[4-(3-hydroxyprop-1-ynyl)-3-methyl-7-[4-(trifluoromethoxy)phenyl]benzimidazol-5-yl]methyl]prop-2-enamide2015512: Displacement of biotinylated lipid pocket probes from His-tagged TEAD4 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assayic500.0030uM
N-[[4-(hydroxymethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1-benzofuran-5-yl]methyl]-N-methylprop-2-enamide2015512: Displacement of biotinylated lipid pocket probes from His-tagged TEAD4 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assayic500.0030uM
(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,4R)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[1-[[(2S)-5-carbamimidamido-2-[[(2S)-3-(6-chloro-1H-indol-3-yl)-2-[[(2S)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]pentanoyl]amino]cyclopropanecarbonyl]amino]pentanoyl]amino]hexanoyl]amino]-3-cyclobutylpropanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carboxylic acid1634096: Inhibition of human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) interaction with N-biotinylated YAP (60 to 100 residues) incubated for 2 hrs by by TR-FRET assayic500.0090uM
1-[3-[4-ethynyl-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one2020151: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assayic500.0090uM
(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,4R)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-3-(6-chloro-1H-indol-3-yl)-2-[[(2S)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-cyclobutylpropanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carboxylic acid1634096: Inhibition of human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) interaction with N-biotinylated YAP (60 to 100 residues) incubated for 2 hrs by by TR-FRET assayic500.0160uM
(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-3-(6-chloro-1H-indol-3-yl)-2-[[(2S)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-cyclobutylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carboxylic acid1634096: Inhibition of human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) interaction with N-biotinylated YAP (60 to 100 residues) incubated for 2 hrs by by TR-FRET assayic500.0450uM
(2S)-1-[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid1634096: Inhibition of human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) interaction with N-biotinylated YAP (60 to 100 residues) incubated for 2 hrs by by TR-FRET assayic500.0560uM
2-[anilino(phenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676394: Binding affinity to nonacylated N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells assessed as inhibition of protein-FAM-YAP (50 to 100 residues) interaction preincubated for 10 mins followed by FAM YAP addition and measured after 1 hr by fluorescence assayic500.0700uM
N-[5-cyano-4-[(E)-2-(4,4-difluorocyclohexyl)ethenyl]-2-pyridinyl]prop-2-enamide2007283: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 30 mins followed by biotinylated lipid pocket addition and measured after 60 mins by TR-FRET assayic500.1000uM
N-[7-[(E)-2-(4,4-difluorocyclohexyl)ethenyl]-4-fluoro-2,3-dihydro-1-benzofuran-5-yl]prop-2-enamide2007283: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 30 mins followed by biotinylated lipid pocket addition and measured after 60 mins by TR-FRET assayic500.1000uM
N-[6-methoxy-5-[(E)-2-[4-(trifluoromethyl)cyclohexyl]ethenyl]pyridazin-3-yl]prop-2-enamide2007283: Inhibition of His-tagged TEAD4 (unknown origin) preincubated for 30 mins followed by biotinylated lipid pocket addition and measured after 60 mins by TR-FRET assayic500.1000uM
2-[anilino-(2-fluorophenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.1000uM
N-[4-(naphthalen-2-ylmethyl)phenyl]ethenesulfonamide1580415: Inhibition of N-terminal His6 tagged human TEAD4-YBD (217 to 434 residues) expressed in Escherichia coli C43 (DE3) cells assessed as reduction in autopalmitoylation preincubated for 2 hrs followed by palmitoyl alkyne-coenzyme A addition and measured after 30 mins by immunoblot analysisic500.1970uM
2-[anilino(naphthalen-2-yl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.2000uM
2-[(3-fluoroanilino)-phenylmethyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.2000uM
2-[anilino-(4-bromophenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.2000uM
2-[anilino-(4-propan-2-ylphenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.2000uM
2-[anilino-(4-methylphenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.2000uM
5-methoxy-4-[3-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile1964894: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assayic500.2000uM
(2S)-1-[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-3-(6-chloro-1H-indol-3-yl)-2-[[(2S)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-cyclobutylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid1634096: Inhibition of human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) interaction with N-biotinylated YAP (60 to 100 residues) incubated for 2 hrs by by TR-FRET assayic500.2160uM
3-hydroxy-6-(hydroxymethyl)-2-[phenyl-(pyridin-2-ylamino)methyl]pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.3000uM
4-[[[3-hydroxy-6-(hydroxymethyl)-4-oxopyran-2-yl]-phenylmethyl]amino]benzamide1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.3000uM
3-hydroxy-6-(hydroxymethyl)-2-[[(4-methyl-2-pyridinyl)amino]-phenylmethyl]pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.3000uM
2-[anilino-(4-fluorophenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.3000uM
4-[anilino-[3-hydroxy-6-(hydroxymethyl)-4-oxopyran-2-yl]methyl]benzamide1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.3000uM
2-[(2-fluorophenyl)-(pyridin-2-ylamino)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.3000uM
2-[(benzylamino)-phenylmethyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.4000uM
2-[(4-bromophenyl)-(pyridin-2-ylamino)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.4000uM
4-[3-(trifluoromethyl)anilino]-1,3,3a,4,5,6,7,7a-octahydroisoindole-2-carbonitrile1964903: Inhibition of TEAD4 (unknown origin) transfected in human HEK293 cells co-transfected with renilla plasmid assessed as inhibition of transcriptional activity incubated for 24 hrs by dual Glo-luciferase reporter assayic500.4000uM
(2S)-1-[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-3-(6-chloro-1H-indol-3-yl)-2-[[(2S)-pyrrolidine-2-carbonyl]amino]propanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]hexanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid1634096: Inhibition of human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) interaction with N-biotinylated YAP (60 to 100 residues) incubated for 2 hrs by by TR-FRET assayic500.4090uM
tert-butyl 4-[[1-(6-chloro-1H-indol-3-yl)-2-oxo-2-[[(1S,2S,4S)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]amino]ethyl]-[[1-[(6-methylimidazo[1,2-a]pyridin-2-yl)methyl]triazol-4-yl]methyl]amino]-4-oxobutanoate2007261: Inhibition of N-terminal His-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-codonPlus (DE3)-RIPL cells by fluorescence polarisation assayic500.4100uM
2-[anilino(pyridin-2-yl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.5000uM
tert-butyl 4-[[1-(6-chloro-1H-indol-3-yl)-2-oxo-2-[(1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]ethyl]-[[1-[(7-methylimidazo[1,2-a]pyridin-2-yl)methyl]triazol-4-yl]methyl]amino]-4-oxobutanoate1916164: Inhibition of YAP binding to human TEAD4 by fluorescence polarization assayic500.5100uM
5-fluoro-4-[3-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile1964894: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assayic500.6000uM
2-chloro-1-[2-[3-(trifluoromethyl)anilino]phenyl]ethanone1676397: Inhibition of CPM binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by CPM addition and measured after 1 hr by fluorescence assayic500.8000uM
2-[1,3-dihydroisoindol-2-yl(phenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one1676399: Inhibition of FITC-labeled palmitate tracer binding to N-terminal His6-tagged human TEAD4 (217 to 434 residues) expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL cells preincubated for 10 mins followed by FITC-labeled palmitate tracer addition and measured after 1 hr by fluorescence assayic500.9000uM
2-(3-chloro-N-(2-chloroacetyl)anilino)-N-(2-phenylethyl)-2-thiophen-2-ylacetamide1977251: Inhibition of GST-tagged TEAD4 (217 to 434 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/FAM-labelled YAP1 (60 to 99 residues)(unknown origin) protein-protein interaction preincubated for 48 hrs at 4 degree C with TEAD4 followed by fluorescent labelled YAP1 addition by fluorescence polarization assayic500.9000uM
3-[(2-chloroacetyl)amino]-1-benzofuran-2-carboxamide1977244: Inhibition of GST-tagged TEAD4 (217 to 434 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/FAM-labelled YAP1 (60 to 99 residues)(unknown origin) protein-protein interaction preincubated for 24 hrs at 4 degree C with TEAD4 followed by fluorescent labelled YAP1 addition by fluorescence polarization assayic500.9000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidincreases expression, increases methylation3
sodium arsenitedecreases expression, increases abundance2
Air Pollutantsaffects cotreatment, increases abundance, increases oxidation, decreases expression2
Benzo(a)pyreneaffects methylation, decreases methylation2
Nickelincreases expression2
Tobacco Smoke Pollutionincreases expression2
Cyclosporinedecreases expression2
Cadmium Chloridedecreases expression2
tert-Butylhydroperoxideaffects expression, decreases expression2
Particulate Matterdecreases expression, decreases reaction, increases abundance2
alpha-pineneaffects cotreatment, increases oxidation, increases abundance1
arseniteaffects binding, increases reaction1
zinc chromatedecreases expression, increases abundance1
benzo(e)pyreneincreases methylation1
potassium chromate(VI)affects cotreatment, decreases expression1
aflatoxin B2decreases methylation, increases methylation1
methacrylaldehydeincreases oxidation, increases abundance, affects cotreatment1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression1
beta-methylcholineaffects expression1
epigallocatechin gallatedecreases expression, affects cotreatment1
chromium hexavalent iondecreases expression, increases abundance1
seocalcitoldecreases expression1
rofecoxibincreases expression1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amidedecreases expression, decreases reaction1
jinfukangaffects cotreatment, decreases expression1
incobotulinumtoxinAdecreases expression1
NSC 689534affects binding, decreases expression1
theaflavin-3,3’-digallateaffects expression1
Resveratrolaffects cotreatment, decreases expression1
Sunitinibincreases expression1

ChEMBL screening assays

131 unique, capped per target: 131 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4120896BindingBinding affinity to human His-tagged TEAD4 YBD (217 to 434 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by ITC assayTargeting Transcriptional Enhanced Associate Domains (TEADs). — J Med Chem

Cellosaurus cell lines

8 cell lines: 4 embryonic stem cell, 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_A7F8SEES3-1V human TEAD4, clone1Embryonic stem cellMale
CVCL_A7F9SEES3-1V human TEAD4, clone2Embryonic stem cellMale
CVCL_A7G0SEES3-1V human TEAD4, clone3Embryonic stem cellMale
CVCL_A8RDWAe001-A-68Embryonic stem cellMale
CVCL_B1HXAbcam A-549 TEAD4 KOCancer cell lineMale
CVCL_B3J5Abcam HEK293T TEAD4 KOTransformed cell lineFemale
CVCL_TR86HAP1 TEAD4 (-) 1Cancer cell lineMale
CVCL_XU16HAP1 TEAD4 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): narcolepsy-cataplexy syndrome