TEAD2

Summary

TEAD2 (TEA domain transcription factor 2, HGNC:11715) is a protein-coding gene on chromosome 19q13.33, encoding Transcriptional enhancer factor TEF-4 (Q15562). 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.

Enables several functions, including DNA-binding transcription factor activity; disordered domain specific binding activity; and transcription coactivator binding activity. Involved in hippo signaling; positive regulation of DNA-templated transcription; and protein-containing complex assembly. Located in cytosol and nucleoplasm. Part of TEAD-YAP complex.

Source: NCBI Gene 8463 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 72 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001256660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11715
Approved symbol	TEAD2
Name	TEA domain transcription factor 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TEF-4, ETF, TEF4
Ensembl gene	ENSG00000074219
Ensembl biotype	protein_coding
OMIM	601729
Entrez	8463

Gene structure

Transcript identifiers

Ensembl transcripts: 96 — 93 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000311227, ENST00000377214, ENST00000539846, ENST00000593945, ENST00000595233, ENST00000596757, ENST00000598397, ENST00000598810, ENST00000598823, ENST00000601519, ENST00000889919, ENST00000889920, ENST00000889921, ENST00000889922, ENST00000889923, ENST00000889924, ENST00000889925, ENST00000889926, ENST00000889927, ENST00000889928, ENST00000889929, ENST00000889930, ENST00000889931, ENST00000889932, ENST00000889933, ENST00000889934, ENST00000889935, ENST00000889936, ENST00000889937, ENST00000889938, ENST00000889939, ENST00000889940, ENST00000889941, ENST00000889942, ENST00000889943, ENST00000889944, ENST00000889945, ENST00000889946, ENST00000937196, ENST00000937197, ENST00000937198, ENST00000937199, ENST00000937200, ENST00000937201, ENST00000937202, ENST00000937203, ENST00000937204, ENST00000937205, ENST00000937206, ENST00000937207, ENST00000937208, ENST00000937209, ENST00000937210, ENST00000937211, ENST00000937212, ENST00000937213, ENST00000937214, ENST00000937215, ENST00000937216, ENST00000937217, ENST00000937218, ENST00000937219, ENST00000937220, ENST00000937221, ENST00000937222, ENST00000937223, ENST00000937224, ENST00000937225, ENST00000937226, ENST00000937227, ENST00000937228, ENST00000937229, ENST00000937230, ENST00000937231, ENST00000937232, ENST00000937233, ENST00000937234, ENST00000937235, ENST00000937236, ENST00000937237, ENST00000937238, ENST00000937239, ENST00000937240, ENST00000937241, ENST00000937242, ENST00000937243, ENST00000937244, ENST00000937245, ENST00000937246, ENST00000937247, ENST00000937248, ENST00000944221, ENST00000944222, ENST00000944223, ENST00000944224, ENST00000944225

RefSeq mRNA: 6 — MANE Select: NM_001256660 NM_001256658, NM_001256659, NM_001256660, NM_001256661, NM_001256662, NM_003598

CCDS: CCDS12761, CCDS58670, CCDS58671, CCDS59406

Canonical transcript exons

ENST00000593945 — 13 exons

Exon	Start	End
ENSE00000719994	49347190	49347363
ENSE00000873545	49343231	49343398
ENSE00000954739	49342438	49342590
ENSE00000954740	49359844	49360081
ENSE00003090606	49362333	49362416
ENSE00003489584	49355959	49355970
ENSE00003518218	49351301	49351365
ENSE00003535692	49357252	49357314
ENSE00003583705	49355148	49355206
ENSE00003585958	49359435	49359499
ENSE00003626518	49355312	49355419
ENSE00003671522	49348703	49348845
ENSE00003902660	49340595	49341437

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 96.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7386 / max 114.7297, expressed in 1413 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182004	10.5123	1402
182003	2.2263	777

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	96.00	silver quality
apex of heart	UBERON:0002098	95.67	gold quality
ganglionic eminence	UBERON:0004023	94.39	gold quality
embryo	UBERON:0000922	94.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.15	gold quality
lower esophagus	UBERON:0013473	94.09	gold quality
tendon of biceps brachii	UBERON:0008188	93.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.57	gold quality
heart left ventricle	UBERON:0002084	93.55	gold quality
cardiac ventricle	UBERON:0002082	93.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.33	gold quality
kidney epithelium	UBERON:0004819	93.32	gold quality
right atrium auricular region	UBERON:0006631	93.22	gold quality
smooth muscle tissue	UBERON:0001135	93.12	gold quality
cardiac atrium	UBERON:0002081	93.06	gold quality
ventricular zone	UBERON:0003053	93.03	gold quality
endocervix	UBERON:0000458	92.77	gold quality
left uterine tube	UBERON:0001303	92.76	gold quality
heart	UBERON:0000948	92.63	gold quality
body of uterus	UBERON:0009853	92.47	gold quality
stromal cell of endometrium	CL:0002255	92.02	gold quality
left ventricle myocardium	UBERON:0006566	91.99	silver quality
upper arm skin	UBERON:0004263	91.96	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.60	gold quality
right ovary	UBERON:0002118	91.50	gold quality
body of tongue	UBERON:0011876	91.44	silver quality
myocardium	UBERON:0002349	91.25	silver quality
mucosa of stomach	UBERON:0001199	91.17	gold quality
omental fat pad	UBERON:0010414	91.17	gold quality
peritoneum	UBERON:0002358	91.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.41

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
EGFR	Unknown
ME1	Activation
PAX3	Activation
PCYT1A	Unknown
POU5F1	Activation
TP53	Unknown

JASPAR motifs

Motif	Name	Family
MA1121.1	TEAD2	TEF-1-related factors
MA1121.2	TEAD2	TEF-1-related factors

JASPAR matrix evidence (PMIDs): PMID:9571041

Upstream regulators (CollecTRI, top): SOX11, YAP1

miRNA regulators (miRDB)

55 targeting TEAD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024

Literature-anchored findings (GeneRIF, showing 7)

• structural and functional analysis of the YAP-binding domain of human TEAD2 (PMID:20368466)
• TAZ negatively regulate transcription of DeltaNp63 through TEAD1,2,3 and 4 transcription factors. (PMID:25995450)
• the increased cisplatin sensitivity induced by miR608 overexpression was reversed by transfection of TEAD2 in nonsmall cell lung cancer (NSCLC) cells. The present data suggested that miR608 may represent a novel candidate biomarker for the evaluation of cisplatin sensitivity in patients with NSCLC. (PMID:31485614)
• Multiple-CoA dehydrogenase deficiency (MADD) is an inborn disorder of fatty acid and amino acid metabolism caused by mutations in the genes encoding for human electron transfer flavoprotein (ETF) and its partner electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO). Conformational analysis of the riboflavin-responsive ETF:QO-p.Pro456Leu variant associated with mild multiple acyl-CoA dehydrogenase deficiency. (PMID:32087359)
• TEAD2 as a novel prognostic factor for hepatocellular carcinoma. (PMID:32323824)
• A Therapeutically Targetable TAZ-TEAD2 Pathway Drives the Growth of Hepatocellular Carcinoma via ANLN and KIF23. (PMID:36894036)
• A TEAD2-Driven Endothelial-Like Program Shapes Basal-Like Differentiation and Metastasis of Pancreatic Cancer. (PMID:36907523)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tead2	ENSMUSG00000030796
rattus_norvegicus	Tead2	ENSRNOG00000020695

Paralogs (3): TEAD3 (ENSG00000007866), TEAD1 (ENSG00000187079), TEAD4 (ENSG00000197905)

Protein

Protein identifiers

Transcriptional enhancer factor TEF-4 — Q15562 (reviewed: Q15562)

Alternative names: TEA domain family member 2

All UniProt accessions (3): Q15562, M0R1A5, M0R290

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 to the SPH and GT-IIC ’enhansons’ (5’-GTGGAATGT-3’). May be involved in the gene regulation of neural development. Binds to the M-CAT motif.

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

Subcellular location. Nucleus.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15562-1	1	yes
Q15562-2	2
Q15562-3	3
Q15562-4	4

RefSeq proteins (6): NP_001243587, NP_001243588, NP_001243589, NP_001243590, NP_001243591, NP_003589 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000818	TEA/ATTS_dom	Domain
IPR016361	TEF_metazoa	Family
IPR038096	TEA/ATTS_sf	Homologous_superfamily
IPR041086	YBD	Domain
IPR050937

Pfam: PF01285, PF17725

UniProt features (35 total): strand 14, helix 6, compositionally biased region 4, splice variant 3, region of interest 3, turn 2, chain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6UYB	X-RAY DIFFRACTION	1.54
7TYP	X-RAY DIFFRACTION	1.6
6UYC	X-RAY DIFFRACTION	1.66
7TYU	X-RAY DIFFRACTION	1.78
7TYQ	X-RAY DIFFRACTION	1.88
7OYJ	X-RAY DIFFRACTION	1.91
8POM	X-RAY DIFFRACTION	1.95
3L15	X-RAY DIFFRACTION	2
5EMV	X-RAY DIFFRACTION	2
6S60	X-RAY DIFFRACTION	2
5HGU	X-RAY DIFFRACTION	2.05
8PUX	X-RAY DIFFRACTION	2.05
8RXV	X-RAY DIFFRACTION	2.05
8P29	X-RAY DIFFRACTION	2.06
8RYC	X-RAY DIFFRACTION	2.09
6S6J	X-RAY DIFFRACTION	2.1
6VAH	X-RAY DIFFRACTION	2.11
9Q1N	X-RAY DIFFRACTION	2.13
6S69	X-RAY DIFFRACTION	2.15
7T2L	X-RAY DIFFRACTION	2.15
9YK2	X-RAY DIFFRACTION	2.16
5DQE	X-RAY DIFFRACTION	2.18
6S66	X-RAY DIFFRACTION	2.2
8PON	X-RAY DIFFRACTION	2.2
8PUY	X-RAY DIFFRACTION	2.2
6S64	X-RAY DIFFRACTION	2.22
8E1O	X-RAY DIFFRACTION	2.25
9Q1O	X-RAY DIFFRACTION	2.26
8RXL	X-RAY DIFFRACTION	2.29
5DQ8	X-RAY DIFFRACTION	2.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15562-F1	72.59	0.38

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-8951671	RUNX3 regulates YAP1-mediated transcription
R-HSA-9796292	Formation of axial mesoderm
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878159	Transcriptional regulation by RUNX3
R-HSA-9758941	Gastrulation

MSigDB gene sets: 166 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_HIPPO_SIGNALING, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, CAGCTG_AP4_Q5, GOBP_LATERAL_MESODERM_DEVELOPMENT, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP

GO Biological Process (18): vasculogenesis (GO:0001570), neural tube closure (GO:0001843), embryonic heart tube morphogenesis (GO:0003143), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), notochord development (GO:0030903), hippo signaling (GO:0035329), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), paraxial mesoderm development (GO:0048339), lateral mesoderm development (GO:0048368), embryonic organ development (GO:0048568), protein-containing complex assembly (GO:0065003), cellular response to retinoic acid (GO:0071300), regulation of stem cell differentiation (GO:2000736), nervous system development (GO:0007399), mesenchyme development (GO:0060485)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription factor activity (GO:0003700), disordered domain specific binding (GO:0097718), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytosol (GO:0005829), TEAD-YAP complex (GO:0140552)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Generic Transcription Pathway	2
Transcriptional regulation by RUNX3	1
Gastrulation	1
Regulation of PD-L1(CD274) expression	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
mesoderm development	2
mesenchyme development	2
animal organ development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cell differentiation	1
blood vessel morphogenesis	1
primary neural tube formation	1
tube closure	1
heart morphogenesis	1
embryonic heart tube development	1
embryonic organ morphogenesis	1
embryonic morphogenesis	1
epithelial tube morphogenesis	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
embryonic organ development	1
intracellular signal transduction	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
embryo development	1
cellular component assembly	1
protein-containing complex organization	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
regulation of cell differentiation	1
stem cell differentiation	1
system development	1
tissue development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription coregulator binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1

Protein interactions and networks

STRING

1727 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TEAD2	YAP1	P46937	965
TEAD2	VGLL4	Q14135	741
TEAD2	CSH1	P01243	666
TEAD2	LATS1	O95835	636
TEAD2	LATS2	Q9NRM7	625
TEAD2	SOX2	P48431	618
TEAD2	SAV1	Q9H4B6	601
TEAD2	TAFAZZIN	Q16635	591
TEAD2	WWTR1	Q9GZV5	586
TEAD2	CCN1	O00622	528
TEAD2	CCN2	P29279	501
TEAD2	NF2	P35240	463
TEAD2	EP300	Q09472	460
TEAD2	VGLL1	Q99990	449
TEAD2	MOB1A	Q9H8S9	442

IntAct

42 interactions, top by confidence:

A	B	Type	Score
TEAD2	YAP1	psi-mi:“MI:0407”(direct interaction)	0.820
TEAD2	YAP1	psi-mi:“MI:2364”(proximity)	0.820
TEAD2	YAP1	psi-mi:“MI:0914”(association)	0.820
BCL2L15	TEAD2	psi-mi:“MI:0915”(physical association)	0.610
TEAD2	BCL2L15	psi-mi:“MI:0915”(physical association)	0.610
USF2	TEAD2	psi-mi:“MI:0915”(physical association)	0.560
TEAD2	USF2	psi-mi:“MI:0915”(physical association)	0.560
YAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
TEAD2	TEAD1	psi-mi:“MI:0914”(association)	0.530
TEAD4	PARN	psi-mi:“MI:0914”(association)	0.530
TEAD2	SAA2	psi-mi:“MI:0915”(physical association)	0.490
SAA2	TEAD2	psi-mi:“MI:0915”(physical association)	0.490
TEAD2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
TEAD2	E6	psi-mi:“MI:0915”(physical association)	0.370
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
TEAD2	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
TEAD4	LYPLA1	psi-mi:“MI:0914”(association)	0.350
YAP1	TEAD1	psi-mi:“MI:0914”(association)	0.350
TEAD2	FLOT1	psi-mi:“MI:0914”(association)	0.350
TEAD4	VGLL3	psi-mi:“MI:0914”(association)	0.350
FBXW7	TEAD2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (150): TEAD2 (Two-hybrid), BCL2L15 (Two-hybrid), TEAD2 (Affinity Capture-RNA), TEAD2 (Affinity Capture-RNA), TEAD2 (Affinity Capture-MS), TEAD2 (Synthetic Lethality), YAP1 (FRET), SMARCA5 (Affinity Capture-MS), CHD4 (Affinity Capture-MS), SATB2 (Affinity Capture-MS), TRIM3 (Affinity Capture-MS), BAZ1A (Affinity Capture-MS), CHD1L (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), PDS5A (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JV04, A9ZLX4, F1N4M2, F1RA39, F6QZ15, O54828, P41154, P48301, P49805, Q02225, Q08D35, Q13191, Q13370, Q14432, Q14DG7, Q15562, Q2VPU4, Q3B7M3, Q3TTA7, Q3UN70, Q4V7W5, Q5FWH3, Q5RHD1, Q5SGD7, Q61409, Q62739, Q62865, Q63085, Q66IV1, Q68EF0, Q6DFR2, Q6GQL0, Q6NRE7, Q80VG1, Q8BMI3, Q8BML1, Q8K4S7, Q8TE85, Q920B0, Q923Q2

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

2 interactions.

A	Effect	B	Mechanism
WWTR1	up-regulates	TEAD2	binding
YAP1	up-regulates	TEAD2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2285 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49342432:CATCA:C	donor_loss	1.0000
19:49342433:ATCAC:A	donor_loss	1.0000
19:49342434:TCACC:T	donor_loss	1.0000
19:49342435:CA:C	donor_loss	1.0000
19:49342436:ACCT:A	donor_loss	1.0000
19:49342437:C:CG	donor_loss	1.0000
19:49342597:C:CT	acceptor_gain	1.0000
19:49342597:C:T	acceptor_gain	1.0000
19:49342598:A:T	acceptor_gain	1.0000
19:49343395:CCGC:C	acceptor_gain	1.0000
19:49343396:CGCC:C	acceptor_gain	1.0000
19:49343397:GCC:G	acceptor_loss	1.0000
19:49343398:CCTG:C	acceptor_loss	1.0000
19:49343399:CTGG:C	acceptor_loss	1.0000
19:49343400:T:G	acceptor_loss	1.0000
19:49347198:TG:T	donor_gain	1.0000
19:49347379:C:CT	acceptor_gain	1.0000
19:49348701:A:AC	donor_gain	1.0000
19:49348702:C:CC	donor_gain	1.0000
19:49348844:CC:C	acceptor_gain	1.0000
19:49348845:CC:C	acceptor_gain	1.0000
19:49351364:CA:C	acceptor_gain	1.0000
19:49351366:C:CC	acceptor_gain	1.0000
19:49355146:A:AC	donor_gain	1.0000
19:49355147:C:CT	donor_gain	1.0000
19:49355147:CT:C	donor_gain	1.0000
19:49355207:C:CC	acceptor_gain	1.0000
19:49355993:G:GC	acceptor_gain	1.0000
19:49355997:C:CT	acceptor_gain	1.0000
19:49355998:A:T	acceptor_gain	1.0000

AlphaMissense

2919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49341394:G:T	A425D	1.000
19:49342442:A:G	L409P	1.000
19:49342450:G:C	F406L	1.000
19:49342450:G:T	F406L	1.000
19:49342451:A:G	F406S	1.000
19:49342452:A:G	F406L	1.000
19:49342453:G:C	N405K	1.000
19:49342453:G:T	N405K	1.000
19:49342454:T:A	N405I	1.000
19:49342457:T:A	E404V	1.000
19:49342460:A:G	L403P	1.000
19:49342463:A:T	V402D	1.000
19:49342490:A:G	L393P	1.000
19:49342499:A:G	L390S	1.000
19:49342510:G:C	F386L	1.000
19:49342510:G:T	F386L	1.000
19:49342511:A:G	F386S	1.000
19:49342512:A:G	F386L	1.000
19:49342523:T:C	Y382C	1.000
19:49342524:A:G	Y382H	1.000
19:49342529:C:T	C380Y	1.000
19:49343256:C:A	G351V	1.000
19:49343256:C:T	G351D	1.000
19:49343258:A:C	F350L	1.000
19:49343258:A:T	F350L	1.000
19:49343259:A:C	F350C	1.000
19:49343260:A:C	F350V	1.000
19:49343260:A:G	F350L	1.000
19:49343260:A:T	F350I	1.000
19:49347265:G:C	F278L	1.000

dbSNP variants (sampled 300 via entrez): RS1000023181 (19:49354717 A>T), RS1000136176 (19:49354288 G>C), RS1000290461 (19:49353965 T>C,G), RS1000323766 (19:49349018 T>C), RS1000419828 (19:49341816 T>C), RS1000498711 (19:49359692 G>A,T), RS1000717212 (19:49348501 A>G), RS1000873209 (19:49363857 C>A,T), RS1000923304 (19:49347391 G>C), RS1001044638 (19:49342813 C>A), RS1001149238 (19:49352933 C>T), RS1001201757 (19:49354231 C>T), RS1001239604 (19:49353100 CT>C,CTT), RS1001359324 (19:49358260 T>A), RS1001391978 (19:49358459 G>A,C)

Disease associations

OMIM: gene MIM:601729 | 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: yes

ChEMBL targets (4): CHEMBL4523301 (SINGLE PROTEIN), CHEMBL5465558 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066050 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193819 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36,725 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL23588	FLUFENAMIC ACID	2	34,797
CHEMBL32350	PIRLINDOLE	2	1,928

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:

Ligand	Action	Affinity	Parameter
GNE-7883	Binding	8.0	pIC50

ChEMBL bioactivities

34 potent at pChembl≥5 of 46 total, top 33 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL5411200
8.70	Ki	2	nM	CHEMBL6147038
8.52	IC50	3	nM	CHEMBL5419829
8.52	IC50	3	nM	CHEMBL5401444
8.52	IC50	3	nM	CHEMBL5408536
8.52	IC50	3	nM	CHEMBL5403826
8.40	IC50	4	nM	CHEMBL5422959
8.40	IC50	4	nM	CHEMBL5400400
8.40	IC50	4	nM	CHEMBL5432828
8.22	IC50	6	nM	CHEMBL5416415
8.22	IC50	6	nM	CHEMBL5415215
8.21	Kd	6.2	nM	CHEMBL5440009
8.05	IC50	9	nM	CHEMBL5438256
7.77	IC50	17	nM	CHEMBL5428867
7.33	Ki	46.9	nM	CHEMBL6142714
6.64	Kd	229	nM	CHEMBL5417138
6.15	IC50	710	nM	CHEMBL5397201
6.10	IC50	800	nM	CHEMBL5434817
5.92	IC50	1200	nM	CHEMBL5394226
5.77	IC50	1700	nM	CHEMBL5405832
5.68	IC50	2100	nM	CHEMBL5434933
5.66	IC50	2200	nM	CHEMBL5424157
5.64	IC50	2300	nM	CHEMBL5423389
5.62	IC50	2400	nM	CHEMBL5432067
5.58	IC50	2600	nM	CHEMBL242708
5.57	IC50	2700	nM	CHEMBL5394226
5.51	IC50	3100	nM	CHEMBL5421684
5.37	IC50	4300	nM	CHEMBL4763473
5.37	EC50	4300	nM	CHEMBL4763473
5.34	Kd	4600	nM	CHEMBL5089646
5.34	Kd	4600	nM	CHEMBL5170406
5.29	Kd	5100	nM	CHEMBL5082195
5.12	IC50	7500	nM	CHEMBL5431797

PubChem BioAssay actives

33 with measured affinity, of 114 total; 32 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[3-[4-ethynyl-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one	2020149: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assay	ic50	0.0020	uM
N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]methyl]prop-2-ynamide	2020149: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assay	ic50	0.0030	uM
2-chloro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]methyl]prop-2-enamide	2020149: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assay	ic50	0.0030	uM
N-[[4-(hydroxymethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1-benzofuran-5-yl]methyl]ethenesulfonamide	2015510: Displacement of biotinylated lipid pocket probes from His-tagged TEAD2 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0030	uM
1-[3-[9-methyl-6-[4-(trifluoromethoxy)phenyl]purin-2-yl]azetidin-1-yl]prop-2-en-1-one	2015510: Displacement of biotinylated lipid pocket probes from His-tagged TEAD2 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0030	uM
1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one	2020149: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assay	ic50	0.0040	uM
cyclobuten-1-yl-[3-[9-methyl-6-[4-(trifluoromethoxy)phenyl]purin-2-yl]azetidin-1-yl]methanone	2015510: Displacement of biotinylated lipid pocket probes from His-tagged TEAD2 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0040	uM
1-[3-[7-[4-(trifluoromethoxy)phenyl]-[1,3]thiazolo[5,4-d]pyrimidin-5-yl]azetidin-1-yl]prop-2-en-1-one	2015510: Displacement of biotinylated lipid pocket probes from His-tagged TEAD2 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0040	uM
N-[[4-(3-hydroxyprop-1-ynyl)-3-methyl-7-[4-(trifluoromethoxy)phenyl]benzimidazol-5-yl]methyl]prop-2-enamide	2015510: Displacement of biotinylated lipid pocket probes from His-tagged TEAD2 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0060	uM
N-[[4-(hydroxymethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1-benzofuran-5-yl]methyl]-N-methylprop-2-enamide	2015510: Displacement of biotinylated lipid pocket probes from His-tagged TEAD2 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0060	uM
(3R,4R)-1-[3-[(E)-2-(4-chlorophenyl)ethenyl]-4-methoxy-5-methylphenyl]-3,4-dihydroxypyrrolidin-2-one	2007259: Binding affinity to SA sensor chip immobilized N-terminal avi-tagged biotinylated TEAD2 YAP binding domain (unknown origin) assessed as binding constant by SPR analysis	kd	0.0062	uM
2-chloro-N-methyl-N-[[1-[4-(trifluoromethoxy)phenyl]indazol-3-yl]methyl]acetamide	2020149: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assay	ic50	0.0090	uM
(E)-1-[3-[4-chloro-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]-4-hydroxybut-2-en-1-one	2020149: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 0.5 to 4 hrs followed by biotinylated lipid pocket probe addition and measured after 60 min by TR-FRET assay	ic50	0.0170	uM
N-[5-cyano-4-[(E)-2-(4,4-difluorocyclohexyl)ethenyl]-2-pyridinyl]prop-2-enamide	2007281: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 30 mins followed by biotinylated lipid pocket addition and measured after 60 mins by TR-FRET assay	ic50	0.1000	uM
N-[7-[(E)-2-(4,4-difluorocyclohexyl)ethenyl]-4-fluoro-2,3-dihydro-1-benzofuran-5-yl]prop-2-enamide	2007281: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 30 mins followed by biotinylated lipid pocket addition and measured after 60 mins by TR-FRET assay	ic50	0.1000	uM
N-[6-methoxy-5-[(E)-2-[4-(trifluoromethyl)cyclohexyl]ethenyl]pyridazin-3-yl]prop-2-enamide	2007281: Inhibition of His-tagged TEAD2 (unknown origin) preincubated for 30 mins followed by biotinylated lipid pocket addition and measured after 60 mins by TR-FRET assay	ic50	0.1000	uM
N-[5-[(E)-2-(4,4-difluorocyclohexyl)ethenyl]-6-methoxy-3-pyridinyl]methanesulfonamide	2007259: Binding affinity to SA sensor chip immobilized N-terminal avi-tagged biotinylated TEAD2 YAP binding domain (unknown origin) assessed as binding constant by SPR analysis	kd	0.2290	uM
N-[4-(1-adamantyl)phenyl]-2-(1H-1,2,4-triazol-5-ylsulfanyl)acetamide	2007260: Inhibition of TEAD2 (unknown origin) palmitoylation in the presence of alkyne-palmitoyl-CoA	ic50	0.7100	uM
4-[4-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile	1964892: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assay	ic50	0.8000	uM
4-[3-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile	1964892: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assay	ic50	1.2000	uM
5-methoxy-4-[3-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile	1964892: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assay	ic50	1.7000	uM
4-[2-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile	1964892: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assay	ic50	2.1000	uM
4-[3-(trifluoromethyl)anilino]-1,3,3a,4,5,6,7,7a-octahydroisoindole-2-carbonitrile	1964909: Inhibition of TEAD2 (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 assay	ic50	2.2000	uM
2-chloro-1-[3-(furan-2-yl)-5-(4-methylphenyl)-3,4-dihydropyrazol-2-yl]ethanone	1977261: Inhibition of TEAD2 (217 to 447 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 TEAD1 followed by fluorescent labelled YAP1 addition by fluorescence polarization assay	ic50	2.3000	uM
5-fluoro-4-[3-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile	1964892: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assay	ic50	2.4000	uM
2-[anilino(phenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one	1676410: Inhibition of CPM binding to nonacylated N-terminal His6-tagged human TEAD2 (217 to 447 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 assay	ic50	2.6000	uM
2-chloro-1-[3-(2,3-dimethoxyphenyl)-5-(thiophen-2-ylmethyl)-3,4-dihydropyrazol-2-yl]ethanone	1977261: Inhibition of TEAD2 (217 to 447 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 TEAD1 followed by fluorescent labelled YAP1 addition by fluorescence polarization assay	ic50	3.1000	uM
2-chloro-1-[2-[3-(trifluoromethyl)anilino]phenyl]ethanone	2007275: Inhibition of FAM-labelled GST-tagged full-length YAP (60 to 99 residues)(unknown origin)/N-terminal His-tagged TEAD2(217 to 447 residues) (unknown origin)) expressed in Escherichia coli BL21 (DE3) cells by fluorescence polarization assay	ic50	4.3000	uM
4-[4-(benzylcarbamoyl)-3-(3,4-dichlorophenyl)pyrazol-1-yl]butanoic acid	1811165: Binding affinity to eGFP-fused human TEAD2 (217 to 447 residues) expressed in CHO-K1 cells by microscale thermophoresis analysis	kd	4.6000	uM
2-methyl-4-[4-(trifluoromethyl)phenyl]pyrazolo[3,4-b]indole-7-carboxylic acid	1892895: Binding affinity to human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 Star (DE3) by surface plasmon resonance assay	kd	4.6000	uM
3-[3-(3,4-dichlorophenyl)-4-(2-phenylethylcarbamoyl)pyrazol-1-yl]propanoic acid	1811165: Binding affinity to eGFP-fused human TEAD2 (217 to 447 residues) expressed in CHO-K1 cells by microscale thermophoresis analysis	kd	5.1000	uM
4-[2-(trifluoromethyl)anilino]-1,3,3a,4,5,6,7,7a-octahydroisoindole-2-carbonitrile	1964892: Displacement of FAM- labeled YAP1 peptide (60 to 99 residues) from human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization-based competitive binding assay	ic50	7.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	4
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1
Ethanol	increases abundance, affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Copper	decreases expression, affects binding	1
Diazinon	increases methylation	1
Gallic Acid	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Lead	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

56 unique, capped per target: 56 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4423907	Binding	Inhibition of Gal4-fused TEAD2 (unknown origin) interaction with YAP expressed in human HeLa cells assessed as basal transcriptional activity level up to 100 uM after 6 hrs by nanoluciferase reporter gene assay	Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7F5	SEES3-1V human TEAD2, clone1	Embryonic stem cell	Male
CVCL_A7F6	SEES3-1V human TEAD2, clone2	Embryonic stem cell	Male
CVCL_A7F7	SEES3-1V human TEAD2, clone3	Embryonic stem cell	Male
CVCL_AW45	K562 eGFP-TEAD2	Cancer cell line	Female
CVCL_B2QF	Abcam A-549 TEAD2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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