TEAD3

Summary

TEAD3 (TEA domain transcription factor 3, HGNC:11716) is a protein-coding gene on chromosome 6p21.31, encoding Transcriptional enhancer factor TEF-5 (Q99594). 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. It is a selective cancer dependency (DepMap: 11.5% of cell lines).

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 predominantly expressed in the placenta and is involved in the transactivation of the chorionic somatomammotropin-B gene enhancer. Translation of this protein is initiated at a non-AUG (AUA) start codon.

Source: NCBI Gene 7005 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 55 total
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 11.5% of screened cell lines
• MANE Select transcript: NM_003214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11716
Approved symbol	TEAD3
Name	TEA domain transcription factor 3
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	TEF-5, ETFR-1
Ensembl gene	ENSG00000007866
Ensembl biotype	protein_coding
OMIM	603170
Entrez	7005

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000338863, ENST00000402886, ENST00000639578

RefSeq mRNA: 2 — MANE Select: NM_003214 NM_001395214, NM_003214

CCDS: CCDS47414, CCDS93900

Canonical transcript exons

ENST00000338863 — 13 exons

Exon	Start	End
ENSE00001887026	35496898	35497079
ENSE00001953620	35473597	35475157
ENSE00003811673	35478434	35478571
ENSE00003812144	35478275	35478324
ENSE00003812284	35476302	35476435
ENSE00003812528	35475566	35475706
ENSE00003812571	35475336	35475488
ENSE00003812634	35477311	35477372
ENSE00003812937	35479305	35479316
ENSE00003812989	35480312	35480374
ENSE00003813417	35484560	35484624
ENSE00003814104	35475919	35476092
ENSE00003835150	35486461	35486711

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9696 / max 196.4167, expressed in 1448 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73283	13.4719	1441
73284	0.2614	101
73282	0.1939	102
73281	0.0424	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	97.10	gold quality
lower esophagus	UBERON:0013473	97.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.63	gold quality
lower esophagus mucosa	UBERON:0035834	96.44	gold quality
mucosa of stomach	UBERON:0001199	96.28	gold quality
body of uterus	UBERON:0009853	96.05	gold quality
left uterine tube	UBERON:0001303	95.88	gold quality
popliteal artery	UBERON:0002250	95.73	gold quality
tibial artery	UBERON:0007610	95.73	gold quality
aorta	UBERON:0000947	95.10	gold quality
right coronary artery	UBERON:0001625	95.03	gold quality
esophagus	UBERON:0001043	94.42	gold quality
thoracic aorta	UBERON:0001515	94.41	gold quality
ascending aorta	UBERON:0001496	94.37	gold quality
ectocervix	UBERON:0012249	94.31	gold quality
descending thoracic aorta	UBERON:0002345	93.82	gold quality
skin of leg	UBERON:0001511	93.53	gold quality
left coronary artery	UBERON:0001626	93.35	gold quality
endocervix	UBERON:0000458	93.29	gold quality
stromal cell of endometrium	CL:0002255	93.19	gold quality
sigmoid colon	UBERON:0001159	93.01	gold quality
skin of abdomen	UBERON:0001416	92.96	gold quality
saphenous vein	UBERON:0007318	92.90	gold quality
coronary artery	UBERON:0001621	92.80	gold quality
myometrium	UBERON:0001296	92.42	gold quality
apex of heart	UBERON:0002098	92.40	gold quality
esophagus mucosa	UBERON:0002469	92.38	gold quality
transverse colon	UBERON:0001157	92.13	gold quality
right ovary	UBERON:0002118	91.71	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.50
E-GEOD-124858	no	43.92
E-GEOD-99795	no	12.10

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0808.1	TEAD3	TEF-1-related factors

JASPAR matrix evidence (PMIDs): PMID:9571041

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• The paper described that the translation initiation codon for the TEF-5 protein was a non-AUG (AUA) codon. (PMID:10379887)
• Transcription enhancer factor-5 and the GATA-like protein act in a coordinate manner to determine the placental-specific expression of the human 3beta-hydroxysteroid dehydrogenase/isomerase I enzyme (PMID:15131259)
• Data indicate that knockdown of TEAD1/3/4 induces an almost identical cellular senescent phenotype as YAP silencing. (PMID:23576552)
• TAZ negatively regulate transcription of DeltaNp63 through TEAD1,2,3 and 4 transcription factors. (PMID:25995450)
• Sequences at the 9p21.3 risk locus disrupt TEAD factor binding and TEAD3-dependent TGF-beta induction of p16 in HAoSMCs. TEAD3 overexpression induced p16 in HAoSMCs homozygous for the nonrisk coronary disease allele, but not for the risk allele. (PMID:26487755)
• Interaction proteomics revealed that VGLL3 bound TEAD1, TEAD3 and TEAD4 in myoblasts and/or myotubes. (PMID:31138678)
• YAP/TEAD3 signal mediates cardiac lineage commitment of human-induced pluripotent stem cells. (PMID:31541452)
• TEAD1 and TEAD3 Play Redundant Roles in the Regulation of Human Epidermal Proliferation. (PMID:32142794)
• TEAD3 inhibits the proliferation and metastasis of prostate cancer via suppressing ADRBK2. (PMID:36907139)
• The paper described that the translation initiation codon for the TEF-5 protein was a non-AUG (ATA) codon. (PMID:9148898)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tead3b	ENSDARG00000063649
danio_rerio	tead3a	ENSDARG00000074321
mus_musculus	Tead3	ENSMUSG00000002249
rattus_norvegicus	Tead3	ENSRNOG00000000506
caenorhabditis_elegans		WBGENE00001208

Paralogs (3): TEAD2 (ENSG00000074219), TEAD1 (ENSG00000187079), TEAD4 (ENSG00000197905)

Protein

Protein identifiers

Transcriptional enhancer factor TEF-5 — Q99594 (reviewed: Q99594)

Alternative names: DTEF-1, TEA domain family member 3

All UniProt accessions (4): Q99594, A0A1X7SBS4, A0A7P0SNI2, B5MCM0

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 multiple functional elements of the human chorionic somatomammotropin-B gene enhancer.

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

Subcellular location. Nucleus.

Tissue specificity. Preferentially expressed in the placenta.

RefSeq proteins (2): NP_001382143, NP_003205* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000818	TEA/ATTS_dom	Domain
IPR016361	TEF_metazoa	Family
IPR027253	TEF-5	Family
IPR038096	TEA/ATTS_sf	Homologous_superfamily
IPR041086	YBD	Domain
IPR050937

Pfam: PF01285, PF17725

UniProt features (30 total): strand 13, helix 6, region of interest 2, compositionally biased region 2, modified residue 2, initiator methionine 1, chain 1, DNA-binding region 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8P0M	X-RAY DIFFRACTION	1.96
7ZJQ	X-RAY DIFFRACTION	2.1
9IXT	X-RAY DIFFRACTION	2.5
5EMW	X-RAY DIFFRACTION	2.55
7CNL	X-RAY DIFFRACTION	2.6
8ZBH	X-RAY DIFFRACTION	2.6
8ZBG	X-RAY DIFFRACTION	2.67
8A0V	X-RAY DIFFRACTION	2.7
8A0U	X-RAY DIFFRACTION	2.9
9IXS	X-RAY DIFFRACTION	2.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99594-F1	76.53	0.43

Functional residue map

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

Post-translational modifications (2): 2, 148

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-8951671	RUNX3 regulates YAP1-mediated transcription
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
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

MSigDB gene sets: 148 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TATTATA_MIR374, GOBP_NEUROGENESIS, GOBP_HIPPO_SIGNALING, GGGTGGRR_PAX4_03, GCGCTTT_MIR518B_MIR518C_MIR518D, GOBP_ASYMMETRIC_CELL_DIVISION, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, RYTTCCTG_ETS2_B, ELK1_01, POU3F2_02, GOBP_EMBRYO_DEVELOPMENT

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), female pregnancy (GO:0007565), hippo signaling (GO:0035329), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic organ development (GO:0048568), asymmetric neuroblast division (GO:0055059), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): 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 factor activity (GO:0003700), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-5 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
multi-organism reproductive process	1
multi-multicellular organism process	1
intracellular signal transduction	1
positive regulation of DNA-templated transcription	1
embryo development	1
animal organ development	1
asymmetric cell division	1
cell fate commitment	1
neuroblast division	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA-binding transcription factor binding	1
nucleic acid binding	1
binding	1
chromosome	1
nuclear lumen	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TEAD3	YAP1	P46937	882
TEAD3	CSH1	P01243	785
TEAD3	KCNIP3	Q9Y2W7	773
TEAD3	VGLL4	Q14135	738
TEAD3	CSH1	P01243	601
TEAD3	SAV1	Q9H4B6	596
TEAD3	LATS1	O95835	586
TEAD3	WWTR1	Q9GZV5	584
TEAD3	LATS2	Q9NRM7	569
TEAD3	NF2	P35240	536
TEAD3	JUN	P05412	508
TEAD3	GHRHR	Q02643	497
TEAD3	TFAP2A	P05549	496
TEAD3	MCAT	Q8IVS2	493
TEAD3	GHR	P10912	491

IntAct

63 interactions, top by confidence:

A	B	Type	Score
YAP1	MPDZ	psi-mi:“MI:0914”(association)	0.780
TEAD3	WWTR1	psi-mi:“MI:0915”(physical association)	0.750
TEAD3	VGLL1	psi-mi:“MI:0915”(physical association)	0.670
VGLL4	TEAD3	psi-mi:“MI:0915”(physical association)	0.670
TEAD3	VGLL2	psi-mi:“MI:0915”(physical association)	0.560
VGLL3	TEAD3	psi-mi:“MI:0915”(physical association)	0.560
YAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
WWTR1	TEAD1	psi-mi:“MI:0914”(association)	0.530
VGLL4	IRF2BP2	psi-mi:“MI:0914”(association)	0.530
VGLL4	TEAD1	psi-mi:“MI:0914”(association)	0.480
FLOT2	TEAD3	psi-mi:“MI:0915”(physical association)	0.400
SUMO2	TEAD3	psi-mi:“MI:0915”(physical association)	0.370
AP4S1	TEAD3	psi-mi:“MI:0915”(physical association)	0.370
TEAD3	PHB2	psi-mi:“MI:0915”(physical association)	0.370
PIDD1	TEAD3	psi-mi:“MI:0915”(physical association)	0.370
KIFC2	TEAD3	psi-mi:“MI:0915”(physical association)	0.370
CTBP2	TEAD3	psi-mi:“MI:0915”(physical association)	0.370
Yap1	GEMIN2	psi-mi:“MI:0914”(association)	0.350
VGLL4	TEAD1	psi-mi:“MI:0914”(association)	0.350
YAP1	TEAD1	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): VGLL2 (Two-hybrid), TEAD3 (Affinity Capture-MS), TEAD3 (Affinity Capture-MS), TEAD3 (Two-hybrid), WWTR1 (Two-hybrid), STUB1 (Affinity Capture-MS), FASN (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), HSPA4 (Affinity Capture-MS), MCMBP (Affinity Capture-MS), PDHA1 (Affinity Capture-MS), YAP1 (Affinity Capture-MS), TEAD3 (Affinity Capture-MS), TEAD3 (Affinity Capture-MS), TEAD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IXF6, A0JP85, A1A5H6, A5YKK6, O15350, O42400, P28347, P30051, P30052, P38529, P48301, P48984, P70210, P97496, Q02225, Q15561, Q15562, Q15648, Q16206, Q17JT4, Q19849, Q1LUC3, Q3YBR2, Q5FWH3, Q5PPL8, Q5RES4, Q60520, Q62296, Q6GL65, Q6PDG5, Q6ZQ08, Q8BG30, Q8BHR2, Q8R0Z2, Q8R1A4, Q8TAQ2, Q8TC92, Q8TE85, Q90701, Q925J9

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	TEAD3	binding
YAP1	up-regulates	TEAD3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Epigenetic regulation of gene expression	5	11.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	6	45.9×	2e-06
epidermal growth factor receptor signaling pathway	5	32.6×	7e-05
positive regulation of ERK1 and ERK2 cascade	5	11.2×	4e-03
protein stabilization	5	8.8×	7e-03
protein ubiquitination	6	6.5×	7e-03
negative regulation of apoptotic process	7	6.4×	4e-03
positive regulation of gene expression	6	6.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2138 predictions. Top by Δscore:

Variant	Effect	Δscore
6:35475154:CCAC:C	acceptor_gain	1.0000
6:35475155:CACC:C	acceptor_gain	1.0000
6:35475157:CCTG:C	acceptor_loss	1.0000
6:35475158:C:CC	acceptor_gain	1.0000
6:35475159:T:G	acceptor_loss	1.0000
6:35475165:G:C	acceptor_gain	1.0000
6:35475165:G:GC	acceptor_gain	1.0000
6:35475331:CATAC:C	donor_loss	1.0000
6:35475333:TA:T	donor_loss	1.0000
6:35475334:A:AC	donor_gain	1.0000
6:35475334:ACCT:A	donor_loss	1.0000
6:35475335:C:CC	donor_gain	1.0000
6:35475335:C:CT	donor_loss	1.0000
6:35475335:CCTG:C	donor_gain	1.0000
6:35475380:T:TA	donor_gain	1.0000
6:35475484:TCAGT:T	acceptor_gain	1.0000
6:35475485:CAGT:C	acceptor_gain	1.0000
6:35475485:CAGTC:C	acceptor_gain	1.0000
6:35475486:AGT:A	acceptor_gain	1.0000
6:35475487:GT:G	acceptor_gain	1.0000
6:35475487:GTCT:G	acceptor_loss	1.0000
6:35475489:C:CC	acceptor_gain	1.0000
6:35475492:C:CT	acceptor_gain	1.0000
6:35475493:A:T	acceptor_gain	1.0000
6:35475702:TCGGC:T	acceptor_gain	1.0000
6:35475703:CGGC:C	acceptor_gain	1.0000
6:35475703:CGGCC:C	acceptor_gain	1.0000
6:35475707:C:CC	acceptor_gain	1.0000
6:35475712:C:CT	acceptor_gain	1.0000
6:35475917:A:AC	donor_gain	1.0000

AlphaMissense

2860 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:35475057:A:G	L432P	1.000
6:35475057:A:T	L432H	1.000
6:35475064:A:C	Y430D	1.000
6:35475108:A:T	V415D	1.000
6:35475114:G:T	A413D	1.000
6:35475123:A:G	L410P	1.000
6:35475153:A:T	V400D	1.000
6:35475340:A:G	L397P	1.000
6:35475346:G:A	T395I	1.000
6:35475348:G:C	F394L	1.000
6:35475348:G:T	F394L	1.000
6:35475349:A:G	F394S	1.000
6:35475350:A:G	F394L	1.000
6:35475351:G:C	N393K	1.000
6:35475351:G:T	N393K	1.000
6:35475352:T:A	N393I	1.000
6:35475352:T:G	N393T	1.000
6:35475353:T:C	N393D	1.000
6:35475355:T:A	E392V	1.000
6:35475356:C:T	E392K	1.000
6:35475358:A:C	L391R	1.000
6:35475358:A:G	L391P	1.000
6:35475358:A:T	L391Q	1.000
6:35475361:A:T	V390E	1.000
6:35475363:G:C	S389R	1.000
6:35475363:G:T	S389R	1.000
6:35475365:T:G	S389R	1.000
6:35475366:G:C	N388K	1.000
6:35475366:G:T	N388K	1.000
6:35475388:A:G	L381P	1.000

dbSNP variants (sampled 300 via entrez): RS1000009023 (6:35485772 G>A), RS1000060015 (6:35486018 A>G), RS1000149543 (6:35497991 G>C), RS1000268499 (6:35474899 T>C), RS1000418648 (6:35491954 C>T), RS1000478943 (6:35487726 A>AC), RS1000838340 (6:35490815 G>A), RS1000914183 (6:35491070 G>T), RS1000969200 (6:35493345 C>T), RS1001022953 (6:35496638 G>A,T), RS1001091589 (6:35496827 C>A,G,T), RS1001116472 (6:35485483 C>A), RS1001321184 (6:35479000 C>T), RS1001398935 (6:35485168 G>C), RS1001406407 (6:35486846 G>A)

Disease associations

OMIM: gene MIM:603170 | disease phenotypes: MIM:600132, MIM:204000

GenCC curated gene-disease

Mondo (3): retinitis pigmentosa 14 (MONDO:0010827), Leber congenital amaurosis (MONDO:0018998), inherited retinal dystrophy (MONDO:0019118)

Orphanet (3): Leber congenital amaurosis (Orphanet:65), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007856_44	Colorectal cancer or advanced adenoma	4.000000e-08
GCST008362_156	Birth weight	2.000000e-13
GCST008363_50	Offspring birth weight	2.000000e-16
GCST90000025_495	Appendicular lean mass	2.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL4523435 (SINGLE PROTEIN), CHEMBL5465398 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066031 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193819 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,928 (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
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	7.0	pIC50

ChEMBL bioactivities

22 potent at pChembl≥5 of 24 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL5422959
8.44	Ki	3.6	nM	CHEMBL6147038
8.40	IC50	4	nM	CHEMBL5401444
8.40	IC50	4	nM	CHEMBL5438256
8.40	IC50	4	nM	CHEMBL5408536
8.30	IC50	5	nM	CHEMBL5411200
8.15	IC50	7	nM	CHEMBL5415215
8.10	IC50	8	nM	CHEMBL5419829
8.05	IC50	9	nM	CHEMBL5400400
8.05	IC50	9	nM	CHEMBL5432828
8.00	IC50	10	nM	CHEMBL5403826
7.89	IC50	13	nM	CHEMBL5428867
7.56	Ki	27.5	nM	CHEMBL6142714
7.03	IC50	93	nM	CHEMBL5416415
6.80	IC50	160	nM	CHEMBL5421419
6.21	IC50	610	nM	CHEMBL5428462
5.92	IC50	1200	nM	CHEMBL5424157
5.85	Kd	1400	nM	CHEMBL5170406
5.68	IC50	2100	nM	CHEMBL5411973
5.66	IC50	2200	nM	CHEMBL5394226
5.58	IC50	2600	nM	CHEMBL242708
5.01	Kd	9800	nM	CHEMBL5406847

PubChem BioAssay actives

23 with measured affinity, of 96 total; 23 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-[7-[4-(trifluoromethoxy)phenyl]-[1,3]thiazolo[5,4-d]pyrimidin-5-yl]azetidin-1-yl]prop-2-en-1-one	2015511: Displacement of biotinylated lipid pocket probes from His-tagged TEAD3 (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
2-chloro-N-methyl-N-[[1-[4-(trifluoromethoxy)phenyl]indazol-3-yl]methyl]acetamide	2020150: Inhibition of His-tagged TEAD3 (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
2-chloro-N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]methyl]prop-2-enamide	2020150: Inhibition of His-tagged TEAD3 (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
1-[3-[9-methyl-6-[4-(trifluoromethoxy)phenyl]purin-2-yl]azetidin-1-yl]prop-2-en-1-one	2015511: Displacement of biotinylated lipid pocket probes from His-tagged TEAD3 (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-[4-ethynyl-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one	2020150: Inhibition of His-tagged TEAD3 (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	0.0050	uM
N-[[4-(hydroxymethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1-benzofuran-5-yl]methyl]-N-methylprop-2-enamide	2015511: Displacement of biotinylated lipid pocket probes from His-tagged TEAD3 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0070	uM
N-[[4-(hydroxymethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1-benzofuran-5-yl]methyl]ethenesulfonamide	2015511: Displacement of biotinylated lipid pocket probes from His-tagged TEAD3 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0080	uM
1-[3-[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]azetidin-1-yl]prop-2-en-1-one	2020150: Inhibition of His-tagged TEAD3 (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
cyclobuten-1-yl-[3-[9-methyl-6-[4-(trifluoromethoxy)phenyl]purin-2-yl]azetidin-1-yl]methanone	2015511: Displacement of biotinylated lipid pocket probes from His-tagged TEAD3 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0090	uM
N-[[4-(hydroxymethyl)-1-[4-(trifluoromethoxy)phenyl]pyrazolo[3,4-b]pyridin-3-yl]methyl]prop-2-ynamide	2020150: Inhibition of His-tagged TEAD3 (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	0.0100	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	2020150: Inhibition of His-tagged TEAD3 (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	0.0130	uM
N-[[4-(3-hydroxyprop-1-ynyl)-3-methyl-7-[4-(trifluoromethoxy)phenyl]benzimidazol-5-yl]methyl]prop-2-enamide	2015511: Displacement of biotinylated lipid pocket probes from His-tagged TEAD3 (unknown origin) preincubated for 4 hrs followed by lipid pocket probe addition and measured after 60 mins by TR-FRET assay	ic50	0.0930	uM
N-[5-cyano-4-[(E)-2-(4,4-difluorocyclohexyl)ethenyl]-2-pyridinyl]prop-2-enamide	2007282: Inhibition of His-tagged TEAD3 (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	2007282: Inhibition of His-tagged TEAD3 (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	2007282: Inhibition of His-tagged TEAD3 (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
1-[3-(3-phenylmethoxypropyl)-1,3-diazinan-1-yl]prop-2-en-1-one	2007287: Inhibition of N-terminal 6xHis-tagged human TEAD3 auto palmitoylation (209 to 426 residues) expressed in Escherichia coli BL21 (DE3) cells by ABPP assay	ic50	0.1600	uM
1-[4-(2-phenoxyethyl)piperidin-1-yl]prop-2-en-1-one	2007287: Inhibition of N-terminal 6xHis-tagged human TEAD3 auto palmitoylation (209 to 426 residues) expressed in Escherichia coli BL21 (DE3) cells by ABPP assay	ic50	0.6100	uM
4-[3-(trifluoromethyl)anilino]-1,3,3a,4,5,6,7,7a-octahydroisoindole-2-carbonitrile	1964910: Inhibition of TEAD3 (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	1.2000	uM
2-methyl-4-[4-(trifluoromethyl)phenyl]pyrazolo[3,4-b]indole-7-carboxylic acid	1892896: Binding affinity to human TEAD3 (216 to 435 residues) expressed in Escherichia coli BL21 Star (DE3) by surface plasmon resonance assay	kd	1.4000	uM
1-[4-(3-phenylmethoxypropyl)piperazin-1-yl]prop-2-en-1-one	2007287: Inhibition of N-terminal 6xHis-tagged human TEAD3 auto palmitoylation (209 to 426 residues) expressed in Escherichia coli BL21 (DE3) cells by ABPP assay	ic50	2.1000	uM
4-[3-(trifluoromethyl)anilino]-1,3-dihydroisoindole-2-carbonitrile	1964910: Inhibition of TEAD3 (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-[anilino(phenyl)methyl]-3-hydroxy-6-(hydroxymethyl)pyran-4-one	1676411: Inhibition of CPM binding to N-terminal His6-tagged human TEAD3 (216 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 assay	ic50	2.6000	uM
(4S)-4-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-5-[[(3S,6S,9S,12S,16Z,21S)-3-(2-amino-2-oxoethyl)-6-benzyl-21-[[(2S)-1-[[(1S)-1-carboxy-3-methylsulfanylpropyl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]-9-(2-methylpropyl)-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-oxopentanoic acid	2007247: Binding affinity to TEAD 3 (unknown origin) assessed as dissociation constant by fluorescence polarisation assay	kd	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
trichostatin A	affects expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cannabinoids	affects methylation, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Niclosamide	increases expression	1
Phthalic Acids	increases methylation	1
Rotenone	increases expression	1
Selenium	increases expression	1
Selenomethionine	affects expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Lactic Acid	decreases expression	1
Genistein	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

39 unique, capped per target: 39 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4423908	Binding	Inhibition of Gal4-fused TEAD3 (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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03913143	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT00749957	PHASE1/PHASE2	COMPLETED	Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
NCT01208389	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
NCT01496040	PHASE1/PHASE2	COMPLETED	Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65
NCT02781480	PHASE1/PHASE2	COMPLETED	Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)
NCT03913130	PHASE1/PHASE2	TERMINATED	Extension Study to Study PQ-110-001 (NCT03140969)
NCT03920007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D
NCT05203939	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
NCT05906953	PHASE1/PHASE2	RECRUITING	Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
NCT06088992	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02575430	Not specified	COMPLETED	Natural History Study in Inherited Retinal Disease Subjects Caused by Mutations in RPE65 or LRAT
NCT02714816	Not specified	COMPLETED	Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65
NCT02946879	Not specified	COMPLETED	Long-Term Follow-Up Gene Therapy Study for Leber Congenital Amaurosis OPTIRPE65 (Retinal Dystrophy Associated With Defects in RPE65)
NCT02970266	Not specified	COMPLETED	Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families.
NCT07026565	Not specified	NOT_YET_RECRUITING	Psychotherapy Group for Parents of Children With LCA
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study