EYA3

Summary

EYA3 (EYA transcriptional coactivator and phosphatase 3, HGNC:3521) is a protein-coding gene on chromosome 1p35.3, encoding Protein phosphatase EYA3 (Q99504). Tyrosine phosphatase that specifically dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph). ‘Tyr-142’ phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress.

This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator and have a role during development. It can act as a mediator of chemoresistance and cell survival in Ewing sarcoma cells, where this gene is up-regulated via a micro-RNA that binds to the 3’ UTR of the transcript. A similar protein in mice acts as a transcriptional activator. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 2140 — RefSeq curated summary.

At a glance

• Gene–disease (curated): craniofacial microsomia (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 73 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3521
Approved symbol	EYA3
Name	EYA transcriptional coactivator and phosphatase 3
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686C132
Ensembl gene	ENSG00000158161
Ensembl biotype	protein_coding
OMIM	601655
Entrez	2140

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000373863, ENST00000373864, ENST00000373871, ENST00000436342, ENST00000468665, ENST00000471498, ENST00000495923, ENST00000540618, ENST00000898700, ENST00000898701, ENST00000898702, ENST00000898703, ENST00000898704, ENST00000898705, ENST00000898706, ENST00000931306, ENST00000931307, ENST00000931308, ENST00000954597

RefSeq mRNA: 4 — MANE Select: NM_001990 NM_001282560, NM_001282561, NM_001282562, NM_001990

CCDS: CCDS316, CCDS60051, CCDS60052

Canonical transcript exons

ENST00000373871 — 18 exons

Exon	Start	End
ENSE00000896307	27978374	27978474
ENSE00001342083	27988535	27988656
ENSE00001461800	27970344	27974546
ENSE00001924082	28088524	28088610
ENSE00003538852	28057994	28058094
ENSE00003547634	27997320	27997378
ENSE00003554013	28042571	28042650
ENSE00003559336	28010947	28011086
ENSE00003561905	28048383	28048426
ENSE00003572504	27999960	28000049
ENSE00003593064	28017154	28017239
ENSE00003643252	27993400	27993560
ENSE00003644087	28004336	28004419
ENSE00003670115	28013111	28013294
ENSE00003671975	28038839	28038905
ENSE00003676403	27989697	27989811
ENSE00003688686	28035544	28035680
ENSE00003717886	28027789	28027926

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 89.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1096 / max 318.8178, expressed in 1810 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11312	23.2770	1809
11314	0.6354	370
11313	0.1905	63
11311	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	89.24	gold quality
pigmented layer of retina	UBERON:0001782	88.46	gold quality
renal medulla	UBERON:0000362	87.91	gold quality
upper leg skin	UBERON:0004262	87.83	gold quality
epithelium of nasopharynx	UBERON:0001951	87.15	gold quality
ventricular zone	UBERON:0003053	86.42	gold quality
calcaneal tendon	UBERON:0003701	86.26	gold quality
lower esophagus mucosa	UBERON:0035834	86.02	gold quality
oocyte	CL:0000023	85.86	gold quality
epithelium of esophagus	UBERON:0001976	85.80	gold quality
secondary oocyte	CL:0000655	85.72	gold quality
tonsil	UBERON:0002372	85.60	gold quality
trabecular bone tissue	UBERON:0002483	85.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.90	gold quality
colonic mucosa	UBERON:0000317	84.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.19	gold quality
skin of hip	UBERON:0001554	83.98	gold quality
jejunal mucosa	UBERON:0000399	83.71	gold quality
mammary duct	UBERON:0001765	83.60	gold quality
ganglionic eminence	UBERON:0004023	83.57	gold quality
mammalian vulva	UBERON:0000997	83.39	gold quality
endometrium	UBERON:0001295	83.20	gold quality
adrenal tissue	UBERON:0018303	83.12	gold quality
blood	UBERON:0000178	83.11	gold quality
squamous epithelium	UBERON:0006914	83.07	gold quality
colonic epithelium	UBERON:0000397	83.01	gold quality
islet of Langerhans	UBERON:0000006	82.87	gold quality
gingival epithelium	UBERON:0001949	82.79	gold quality
gingiva	UBERON:0001828	82.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	35.70
E-ANND-3	yes	8.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EWSR1, FLI1

miRNA regulators (miRDB)

204 targeting EYA3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587

Literature-anchored findings (GeneRIF, showing 9)

• EYA2 and EYA3 displayed specificity for Tyr-142 of H2A.X (PMID:19351884)
• These studies identify EYA3 as a novel mediator of chemoresistance in Ewing sarcoma and define the molecular mechanisms of both EYA3 overexpression and of EYA3-mediated chemoresistance (PMID:22723308)
• Benzbromarone metabolites and derivatives function as EYA3 inhibitory anti-angiogenic agents. (PMID:24367676)
• WDR1 is an EYA3-specific substrate, which implies that EYA3 is a key modulator of the cytoskeletal reorganization (PMID:29440662)
• Study identifies Eya3 as a regulator of PP2A, a major cellular Ser/Thr phosphatase, and uncovers a mechanism of controlling the stability of a critical oncogene, c-Myc. (PMID:29535359)
• These findings suggest that EYA3’s tyrosine phosphorylation sites are non-equivalent with their phosphorylation levels being under the control of Src-kinase activity and of EYA3’s autodephosphorylation. (PMID:31847183)
• A recurrent missense variant in EYA3 gene is associated with oculo-auriculo-vertebral spectrum. (PMID:33475861)
• Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis. (PMID:34419070)
• Identification of novel mutations in EYA3 and EFTUD2 in a family with craniofacial microsomia: evidence of digenic inheritance. (PMID:37507637)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eya3	ENSDARG00000036100
mus_musculus	Eya3	ENSMUSG00000028886
rattus_norvegicus	Eya3	ENSRNOG00000010396
drosophila_melanogaster	eya	FBGN0000320
caenorhabditis_elegans	eya-1	WBGENE00001377

Paralogs (3): EYA2 (ENSG00000064655), EYA1 (ENSG00000104313), EYA4 (ENSG00000112319)

Protein

Protein identifiers

Protein phosphatase EYA3 — Q99504 (reviewed: Q99504)

Alternative names: Eyes absent homolog 3

All UniProt accessions (2): B1APR7, Q99504

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine phosphatase that specifically dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph). ‘Tyr-142’ phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity. May be involved in development of the eye.

Subunit / interactions. Interacts with SIX1 and DACH1, and probably SIX2, SIX4, SIX5.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Ser-266 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Similarity. Belongs to the HAD-like hydrolase superfamily. EYA family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q99504-1	1	yes
Q99504-2	2
Q99504-3	3
Q99504-4	4
Q99504-5	5

RefSeq proteins (4): NP_001269489, NP_001269490, NP_001269491, NP_001981* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006545	EYA_dom	Domain
IPR028472	EYA	Family
IPR038102	EYA_dom_sf	Homologous_superfamily
IPR042577	EYA_dom_metazoan	Domain

Pfam: PF00702

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (42 total): sequence conflict 21, modified residue 5, splice variant 4, binding site 3, region of interest 2, mutagenesis site 2, compositionally biased region 2, active site 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9C7T	ELECTRON MICROSCOPY	2.7
9N0Y	ELECTRON MICROSCOPY	3.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99504-F1	66.28	0.46

Functional residue map

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

Catalytic / active sites (2): 309 (nucleophile); 311 (proton donor)

Ligand- & substrate-binding residues (3): 309; 311; 537

Post-translational modifications (5): 1, 262, 266, 438, 472

Mutagenesis-validated functional residues (2):

Position	Phenotype
266	fails to form damage-dependent nuclear foci or interact with h2ax.
309	loss of tyrosine phosphatase activity toward h2ax.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

MSigDB gene sets: 221 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_IONIZING_RADIATION, MODULE_255, MODULE_317, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, AP4_Q6, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_ABSENCE_OF_LIGAND, GOBP_REGULATION_OF_RESPONSE_TO_STRESS

GO Biological Process (12): double-strand break repair (GO:0006302), visual perception (GO:0007601), anatomical structure morphogenesis (GO:0009653), response to ionizing radiation (GO:0010212), cell differentiation (GO:0030154), positive regulation of DNA repair (GO:0045739), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), DNA repair (GO:0006281), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974), multicellular organism development (GO:0007275)

GO Molecular Function (6): protein tyrosine phosphatase activity (GO:0004725), metal ion binding (GO:0046872), histone H2AXY142 phosphatase activity (GO:0140793), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA Double Strand Break Response	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	2
anatomical structure development	2
cellular anatomical structure	2
sensory perception of light stimulus	1
developmental process	1
response to radiation	1
cellular developmental process	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
extrinsic apoptotic signaling pathway in absence of ligand	1
negative regulation of signal transduction in absence of ligand	1
negative regulation of extrinsic apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
chromatin organization	1
cellular response to stress	1
multicellular organismal process	1
phosphoprotein phosphatase activity	1
cation binding	1
histone phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EYA3	SIX1	Q15475	848
EYA3	SIX2	Q9NPC8	726
EYA3	TSHB	P01222	692
EYA3	SIX4	Q9UIU6	602
EYA3	DACH1	Q9UI36	598
EYA3	PPP2R2A	P50409	580
EYA3	FGR	P09769	550
EYA3	PAX3	P23760	539
EYA3	DIO3	P55073	531
EYA3	SIX6	O95475	522
EYA3	PAX6	P26367	505
EYA3	H2AX	P16104	501
EYA3	DIO2	Q92813	486
EYA3	TEF	Q10587	468
EYA3	TSHR	P16473	464

IntAct

70 interactions, top by confidence:

A	B	Type	Score
EYA3	APBB2	psi-mi:“MI:0915”(physical association)	0.560
EYA3	ATP1A3	psi-mi:“MI:0915”(physical association)	0.560
EYA3	DNM2	psi-mi:“MI:0915”(physical association)	0.560
EYA3		psi-mi:“MI:0915”(physical association)	0.560
ELAVL4	EYA3	psi-mi:“MI:0915”(physical association)	0.560
HSPD1	EYA3	psi-mi:“MI:0915”(physical association)	0.560
EYA3	MECP2	psi-mi:“MI:0915”(physical association)	0.560
EYA3	NEFL	psi-mi:“MI:0915”(physical association)	0.560
EYA3	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
EYA3	PMP22	psi-mi:“MI:0915”(physical association)	0.560
EYA3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
EYA3	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
EYA3	RNF11	psi-mi:“MI:0915”(physical association)	0.560
HTT	EYA3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (81): EYA3 (Two-hybrid), EYA3 (Affinity Capture-MS), EYA3 (Two-hybrid), EYA3 (Proximity Label-MS), EYA3 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), PTRH2 (Affinity Capture-MS), MTMR2 (Affinity Capture-MS), GRPEL1 (Affinity Capture-MS), FHL2 (Affinity Capture-MS), TMEM126A (Affinity Capture-MS), TSEN34 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), NPPC (Affinity Capture-MS)

ESM2 similar proteins: A0A1P8AS03, A3LX75, A5DDB7, D5MCN2, F4IUY8, F4K1Z0, G4NID8, M2TGT8, M2U3Z7, O13987, O17670, O60167, O61708, O74345, O74412, O95677, P25644, P34643, P53297, P97767, Q05672, Q07998, Q08400, Q09750, Q09801, Q10655, Q10667, Q18273, Q20374, Q20870, Q2L4W6, Q3MK94, Q3S405, Q61X54, Q6E3D2, Q6E3D4, Q6FLG1, Q6FSQ6, Q75BK1, Q7ZT82

Diamond homologs: O00167, O08575, O82162, O95677, P97480, P97767, Q05201, Q58DB6, Q99502, Q99504, Q9YH98, Q9YH99, Q9YHA0, Q9YHA1, Q9Z191, O17670

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EYA3	down-regulates	H2AX	dephosphorylation
EYA3	“up-regulates activity”	Six1/Dach	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3379 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27978369:GTTAC:G	donor_loss	1.0000
1:27978470:CTTAC:C	acceptor_gain	1.0000
1:27988653:CTTT:C	acceptor_gain	1.0000
1:27988657:C:CC	acceptor_gain	1.0000
1:27989691:CCATA:C	donor_loss	1.0000
1:27989692:CATAC:C	donor_loss	1.0000
1:27989693:ATAC:A	donor_loss	1.0000
1:27989694:TAC:T	donor_loss	1.0000
1:27989695:A:AG	donor_loss	1.0000
1:27989696:C:A	donor_loss	1.0000
1:27993398:ACCAC:A	donor_gain	1.0000
1:27993399:CCACC:C	donor_gain	1.0000
1:27993559:TG:T	acceptor_gain	1.0000
1:27993561:C:CC	acceptor_gain	1.0000
1:27997376:CTC:C	acceptor_gain	1.0000
1:27999954:GCTTA:G	donor_loss	1.0000
1:27999955:CTTAC:C	donor_loss	1.0000
1:27999956:TTAC:T	donor_loss	1.0000
1:27999957:TACCT:T	donor_loss	1.0000
1:27999958:A:AC	donor_gain	1.0000
1:27999959:C:CC	donor_gain	1.0000
1:27999959:CCT:C	donor_gain	1.0000
1:28000047:GTCC:G	acceptor_loss	1.0000
1:28000048:TC:T	acceptor_gain	1.0000
1:28000049:CC:C	acceptor_gain	1.0000
1:28000050:C:CC	acceptor_gain	1.0000
1:28004331:ATTAC:A	donor_loss	1.0000
1:28004332:TTAC:T	donor_loss	1.0000
1:28004333:TACCT:T	donor_loss	1.0000
1:28004334:A:T	donor_loss	1.0000

AlphaMissense

3742 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:27974470:A:G	L573P	1.000
1:27974470:A:T	L573H	1.000
1:27974485:A:G	L568S	1.000
1:27974488:G:T	A567D	1.000
1:27974489:C:G	A567P	1.000
1:27974497:A:G	L564P	1.000
1:27974506:A:G	L561P	1.000
1:27974529:C:A	W553C	1.000
1:27974529:C:G	W553C	1.000
1:27974530:C:G	W553S	1.000
1:27974531:A:G	W553R	1.000
1:27974531:A:T	W553R	1.000
1:27974532:G:C	F552L	1.000
1:27974532:G:T	F552L	1.000
1:27974533:A:G	F552S	1.000
1:27974534:A:G	F552L	1.000
1:27978381:G:T	A545D	1.000
1:27978382:C:G	A545P	1.000
1:27978408:C:A	G536V	1.000
1:27978408:C:T	G536E	1.000
1:27978409:C:G	G536R	1.000
1:27978409:C:T	G536R	1.000
1:27978411:A:T	I535N	1.000
1:27978414:A:T	V534E	1.000
1:27978417:A:T	V533E	1.000
1:27978421:A:C	Y532D	1.000
1:27978461:G:C	C518W	1.000
1:27978462:C:T	C518Y	1.000
1:27988546:G:T	A510D	1.000
1:27988547:C:G	A510P	1.000

dbSNP variants (sampled 300 via entrez): RS1000001079 (1:28063252 T>A,C), RS1000008028 (1:28017371 G>A), RS1000038604 (1:28008351 A>T), RS1000059222 (1:28084808 C>G,T), RS1000075812 (1:28075541 C>T), RS1000125905 (1:28028445 T>C), RS1000161413 (1:27980982 G>A), RS1000182712 (1:27988189 T>A), RS1000183081 (1:28057781 T>C), RS1000188285 (1:28036579 G>A), RS1000249637 (1:28081177 G>A), RS1000256628 (1:28069061 C>T), RS1000277459 (1:28035697 A>G), RS1000284719 (1:28035994 T>C), RS1000292611 (1:28015491 T>A,G)

Disease associations

OMIM: gene MIM:601655 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
craniofacial microsomia	Limited	Autosomal dominant

Mondo (1): craniofacial microsomia (MONDO:0015397)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004484_2	Plasma trimethylamine N-oxide levels	4.000000e-08
GCST006614_57	Total cholesterol levels	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005691	plasma trimethylamine N-oxide measurement
EFO:0004574	total cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006053	Goldenhar Syndrome	C05.116.099.370.231.576.410; C05.660.207.231.576.410; C16.131.621.207.231.576.410

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296245 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 9,956 (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
CHEMBL1474963	BENZARONE	4	358
CHEMBL232201	BENZIODARONE	4	1,341
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL224006	POZTINURAD	2	12

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

Binding affinities (BindingDB)

12 measured of 12 human assays (12 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2-ethylbenzofuran-3-yl)(4-hydroxy-3,5-diiodophenyl)methanone	IC50	3400 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(4-hydroxy-3,5-diiodophenyl)(2-methylbenzofuran-3-yl)methanone	IC50	8300 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
4-[(2-butyl-1-benzofuran-3-yl)carbonyl]phenol	IC50	10100 nM	US-9725430: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(3,5-dibromo-4-hydroxyphenyl)(2-ethyl-1-benzofuran-3-yl)methanone	IC50	11000 nM	US-9725430: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(4-hydroxy-3,5-diiodophenyl)-[2-(2-hydroxypropyl)-1-benzofuran-3-yl]methanone	IC50	13800 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(4-hydroxy-3-iodophenyl)-(2-methyl-1-benzofuran-3-yl)methanone	IC50	17500 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(2-Ethylbenzofuran-3-yl)(4-hydroxyphenyl)methanone	IC50	19200 nM	US-9725430: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(3,5-Dibromo-4-hydroxyphenyl)(2-ethyl-6-hydroxy-benzofuran-3-yl)methanone	IC50	27200 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(3,5-Dibromo-4-hydroxyphenyl)(2-ethyl-5-hydroxybenzofuran-3-yl)methanone	IC50	40800 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(3,5-dibromo-4-hydroxyphenyl)-[2-(1-hydroxyethyl)-1-benzofuran-3-yl]methanone	IC50	41900 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(2-Ethyl-5-hydroxybenzofuran-3-yl)(4-hydroxyphenyl)methanone	IC50	73100 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase
(4-hydroxyphenyl)(2-methylbenzofuran-3-yl)methanone	IC50	81100 nM	US-9962362: Use of small molecule inhibitors targeting EYA tyrosine phosphatase

ChEMBL bioactivities

11 potent at pChembl≥5 of 42 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.51	IC50	3100	nM	CHEMBL3526986
5.47	IC50	3400	nM	BENZIODARONE
5.08	IC50	8300	nM	BENZBROMARONE
5.08	IC50	8300	nM	CHEMBL389052

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects methylation, decreases expression, affects cotreatment, increases abundance	5
bisphenol A	increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
trichostatin A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
CPG-oligonucleotide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Benzbromarone	decreases activity	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Theophylline	increases expression	1
Valproic Acid	decreases expression	1
Zinc	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4257240	Binding	Inhibition of human Eya3 isoform 2 (127 to 573 residues) incubated for 30 mins by p-nitrophenylphosphate assay	Use of small molecule inhibitors targeting eya tyrosine phosphatase

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01674439	PHASE2	COMPLETED	Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells
NCT05610878	PHASE1	RECRUITING	Efficacy of Preconditioned Adipose-Derived Stem Cells in Fat Grafting
NCT02224677	Not specified	COMPLETED	Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK)
NCT02494752	Not specified	UNKNOWN	Role of Mesenchymal Stem Cells in Fat Grafting
NCT03806361	Not specified	COMPLETED	Fat Grafts With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children
NCT03861650	Not specified	COMPLETED	Evaluation of Effect of Bone Marrow Aspirate Concentrate on Distracted Mandibular Bone Properties
NCT03869021	Not specified	COMPLETED	Computer Guided for Mandibular Distraction Osteogenesis
NCT04056858	Not specified	COMPLETED	Study of a Candidate Gene Involved in Goldenhar Syndrome.
NCT04351893	Not specified	COMPLETED	Craniofacial Microsomia: Accelerating Understanding of the Significance and Etiology
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.