EPHA8

Summary

EPHA8 (EPH receptor A8, HGNC:3391) is a protein-coding gene on chromosome 1p36.12, encoding Ephrin type-A receptor 8 (P29322). Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

This gene encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system.

Source: NCBI Gene 2046 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 199 total
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020526

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3391
Approved symbol	EPHA8
Name	EPH receptor A8
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	Hek3
Ensembl gene	ENSG00000070886
Ensembl biotype	protein_coding
OMIM	176945
Entrez	2046

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000166244, ENST00000374644

RefSeq mRNA: 2 — MANE Select: NM_020526 NM_001006943, NM_020526

CCDS: CCDS225, CCDS30626

Canonical transcript exons

ENST00000166244 — 17 exons

Exon	Start	End
ENSE00000388454	22569289	22569353
ENSE00000388463	22597676	22597861
ENSE00000388465	22598838	22599047
ENSE00000388468	22601300	22601473
ENSE00000560716	22597312	22597476
ENSE00000560718	22598151	22598212
ENSE00000759471	22596106	22596173
ENSE00000759515	22595230	22595323
ENSE00000759516	22593524	22593686
ENSE00000759532	22593326	22593450
ENSE00000759543	22586480	22586635
ENSE00000859688	22600898	22601088
ENSE00001131796	22588871	22589206
ENSE00001131811	22576217	22576880
ENSE00001156943	22601627	22603595
ENSE00001753689	22600661	22600810
ENSE00003850448	22563489	22563729

Expression profiles

Bgee: expression breadth broad, 65 present calls, max score 89.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3521 / max 51.7936, expressed in 141 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1284	0.3521	141

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	89.36	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.20	gold quality
tibialis anterior	UBERON:0001385	88.86	silver quality
left ventricle myocardium	UBERON:0006566	88.79	gold quality
pancreatic ductal cell	CL:0002079	85.53	silver quality
cerebellar vermis	UBERON:0004720	83.70	gold quality
upper arm skin	UBERON:0004263	83.42	gold quality
ileal mucosa	UBERON:0000331	82.93	silver quality
vena cava	UBERON:0004087	78.70	gold quality
buccal mucosa cell	CL:0002336	78.62	silver quality
lateral globus pallidus	UBERON:0002476	78.25	gold quality
substantia nigra pars compacta	UBERON:0001965	77.83	gold quality
epithelial cell of pancreas	CL:0000083	77.67	gold quality
endothelial cell	CL:0000115	77.44	silver quality
body of tongue	UBERON:0011876	77.43	gold quality
superior surface of tongue	UBERON:0007371	77.23	gold quality
nipple	UBERON:0002030	77.21	gold quality
tongue	UBERON:0001723	77.17	gold quality
pharyngeal mucosa	UBERON:0000355	77.07	gold quality
pericardium	UBERON:0002407	77.04	gold quality
saphenous vein	UBERON:0007318	76.97	gold quality
trachea	UBERON:0003126	76.95	gold quality
pons	UBERON:0000988	76.73	silver quality
pylorus	UBERON:0001166	76.66	gold quality
nasal cavity epithelium	UBERON:0005384	76.57	gold quality
layer of synovial tissue	UBERON:0007616	75.90	gold quality
synovial joint	UBERON:0002217	75.71	gold quality
penis	UBERON:0000989	75.54	gold quality
quadriceps femoris	UBERON:0001377	75.43	gold quality
epithelium of nasopharynx	UBERON:0001951	75.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEIS2, NFIA, NFIB, NFIX, PBX2

miRNA regulators (miRDB)

153 targeting EPHA8, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705

Literature-anchored findings (GeneRIF, showing 9)

• role in stimulated cell migration in presnce of p110 gamma PI-3 kinase (PMID:12681484)
• EphA8 receptor is capable of inducing a sustained increase in MAPK activity, thereby promoting neurite outgrowth in neuronal cells (PMID:15782114)
• RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin. (PMID:22291991)
• Human miR-10a and EphA8 regulate epithelial-mesenchymal transition (EMT) to affect glioma cell migration and invasion. (PMID:25683004)
• High EPHA8 expression is associated with epithelial ovarian cancer. (PMID:26989075)
• Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy…This first study sequencing EPHA genes revealed that low-frequency variants in EPHA6, EPHA5, and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy (PMID:27582484)
• Q-PCR and IHC staining revealed that EphA8 was highly expressed in OTSCC tissues, especially in advanced stage OTSCC tissues. Kaplan-Meier curve showed that high EphA8 expression was significantly associated with poor prognosis. (PMID:30300334)
• EphA8 knockdown also decreased expression of the protease ADAM10 (PMID:31026069)
• EphA8 inhibits cell apoptosis via AKT signaling and is associated with poor prognosis in breast cancer. (PMID:34278497)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epha8	ENSMUSG00000028661
rattus_norvegicus	Epha8	ENSRNOG00000013036

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Ephrin type-A receptor 8 — P29322 (reviewed: P29322)

Alternative names: EPH- and ELK-related kinase, EPH-like kinase 3, Tyrosine-protein kinase receptor EEK

All UniProt accessions (1): P29322

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth.

Subunit / interactions. Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. May also form heterodimers with other ephrin receptors. Interacts with FYN; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PIK3CG; regulates integrin-mediated cell adhesion to substrate. Interacts with TIAM1; regulates clathrin-mediated endocytosis of EPHA8. Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-independent but stimulated by EPHA8 ubiquitination.

Subcellular location. Cell membrane. Cell projection. Early endosome membrane.

Post-translational modifications. Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-616 is critical for association with FYN. Autophosphorylation on Tyr-839 modulates tyrosine kinase activity. Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P29322-1	1	yes
P29322-2	2

RefSeq proteins (2): NP_001006944, NP_065387* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001090	EPH_LBD	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001426	Tyr_kinase_rcpt_V_CS	Conserved_site
IPR001660	SAM	Domain
IPR003961	FN3_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016257	EPH	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR027936	EPH_TM	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050449	Ephrin_rcpt_TKs	Family

Pfam: PF00041, PF00536, PF01404, PF07714, PF14575, PF25599

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (69 total): helix 19, strand 13, sequence variant 9, domain 5, turn 4, glycosylation site 3, region of interest 2, binding site 2, modified residue 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, short sequence motif 1, active site 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3KUL	X-RAY DIFFRACTION	2.15
1UCV	SOLUTION NMR
1X5L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29322-F1	80.63	0.50

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 (1): 760 (proton acceptor)

Ligand- & substrate-binding residues (2): 641–649; 667

Post-translational modifications (2): 616, 839

Glycosylation sites (3): 340, 407, 432

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-3928665	EPH-ephrin mediated repulsion of cells

MSigDB gene sets: 146 (showing top): GOBP_NEURON_MATURATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, TATTATA_MIR374, GOBP_NEUROGENESIS, CACCAGC_MIR138, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_CELL_MATURATION, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_ADHESION_MEDIATED_BY_INTEGRIN, CAATGCA_MIR33, GOBP_RESPONSE_TO_FOLLICLE_STIMULATING_HORMONE, GOBP_EPHRIN_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_HORMONE

GO Biological Process (14): substrate-dependent cell migration (GO:0006929), cell adhesion (GO:0007155), axon guidance (GO:0007411), neuron remodeling (GO:0016322), regulation of cell adhesion (GO:0030155), neuron projection development (GO:0031175), regulation of cell adhesion mediated by integrin (GO:0033628), positive regulation of MAPK cascade (GO:0043410), ephrin receptor signaling pathway (GO:0048013), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to follicle-stimulating hormone stimulus (GO:0071372), protein phosphorylation (GO:0006468), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), nervous system development (GO:0007399)

GO Molecular Function (12): ephrin receptor activity (GO:0005003), GPI-linked ephrin receptor activity (GO:0005004), transmembrane-ephrin receptor activity (GO:0005005), ATP binding (GO:0005524), growth factor binding (GO:0019838), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): plasma membrane (GO:0005886), dendrite (GO:0030425), early endosome membrane (GO:0031901), neuron projection (GO:0043005), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
EPH-Ephrin signaling	2
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of intracellular signal transduction	2
ephrin receptor activity	2
cellular anatomical structure	2
cell migration	1
cellular process	1
axonogenesis	1
neuron projection guidance	1
neuron maturation	1
cell adhesion	1
regulation of cellular process	1
neuron development	1
plasma membrane bounded cell projection organization	1
regulation of cell adhesion	1
cell adhesion mediated by integrin	1
MAPK cascade	1
regulation of MAPK cascade	1
cell surface receptor protein tyrosine kinase signaling pathway	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
response to follicle-stimulating hormone	1
cellular response to gonadotropin stimulus	1
phosphorylation	1
protein modification process	1
enzyme-linked receptor protein signaling pathway	1
system development	1
transmembrane receptor protein tyrosine kinase activity	1
ephrin receptor signaling pathway	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein kinase activity	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

1423 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHA8	EFNA5	P52803	938
EPHA8	EFNA2	O43921	925
EPHA8	EFNA1	P20827	919
EPHA8	EFNA3	P52797	857
EPHA8	EFNB1	P98172	753
EPHA8	EFNB3	Q15768	747
EPHA8	EFNA4	P52798	743
EPHA8	EFNB2	P52799	714
EPHA8	PICK1	Q9NRD5	602
EPHA8	AQP1	P29972	592
EPHA8	RINL	Q6ZS11	525
EPHA8	DAPP1	Q9UN19	489
EPHA8	CRKL	P46109	472
EPHA8	NCK1	P16333	465
EPHA8	MEIS2	O14770	449
EPHA8	HCK	P08631	449

IntAct

23 interactions, top by confidence:

A	B	Type	Score
EPHA8	EFNA5	psi-mi:“MI:0914”(association)	0.610
ABHD15	HSPA8	psi-mi:“MI:0914”(association)	0.530
RAB3A	CHM	psi-mi:“MI:0914”(association)	0.530
PTPRD	EPHA8	psi-mi:“MI:0407”(direct interaction)	0.440
EPHA8	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
EPHA8	LRRK1	psi-mi:“MI:0407”(direct interaction)	0.440
AK4	EPHA8	psi-mi:“MI:0915”(physical association)	0.370
EPHA8	PSMC5	psi-mi:“MI:0915”(physical association)	0.370
EPHA8	G3BP1	psi-mi:“MI:0915”(physical association)	0.370
EPHA8	DARS2	psi-mi:“MI:0915”(physical association)	0.370
EPHA8	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
EPHA8	NDUFA4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350
EPHA7	PLOD2	psi-mi:“MI:0914”(association)	0.350
EPHA8	TNFRSF6B	psi-mi:“MI:0914”(association)	0.350
BTK	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
EFNA5	NBAS	psi-mi:“MI:0914”(association)	0.350
EPHA8	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
INSRR	HNRNPCL2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (173): EPHA8 (Affinity Capture-Western), EFNA5 (Affinity Capture-MS), ENDOG (Affinity Capture-MS), EPHA8 (Reconstituted Complex), EPHA8 (Reconstituted Complex), EPHA8 (Affinity Capture-MS), EPHA8 (Affinity Capture-RNA), PIK3CG (Affinity Capture-Western), ENDOG (Affinity Capture-MS), EFNA5 (Affinity Capture-MS), EPHA8 (Affinity Capture-MS), BMP1 (Affinity Capture-MS), TYMP (Affinity Capture-MS), FYN (Affinity Capture-Western), FYN (Reconstituted Complex)

ESM2 similar proteins: A0A0U1RPR8, O02740, O08644, O09127, O15197, O19179, O73875, O73878, P0C0K6, P0C0K7, P14616, P16067, P20594, P21709, P26770, P29317, P29322, P35590, P46197, P51839, P51840, P51841, P51842, P52333, P52785, P54753, P54754, P54760, P54761, P55203, P55205, Q02846, Q03146, Q06805, Q06806, Q08345, Q1KL86, Q5JZY3, Q5SDA5, Q60750

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
EFNA1	up-regulates	EPHA8	binding
EPHA8	“up-regulates activity”	EPHA8	phosphorylation
EFNA2	up-regulates	EPHA8	binding
EFNA3	up-regulates	EPHA8	binding
EFNA5	up-regulates	EPHA8	binding
NFIA	“up-regulates quantity”	EPHA8	“transcriptional regulation”
NFIB	“up-regulates quantity”	EPHA8	“transcriptional regulation”
NFIX	“up-regulates quantity”	EPHA8	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	181
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3289 predictions. Top by Δscore:

Variant	Effect	Δscore
1:22589204:CAG:C	donor_loss	1.0000
1:22589205:AGG:A	donor_loss	1.0000
1:22589206:GGT:G	donor_loss	1.0000
1:22589207:G:A	donor_loss	1.0000
1:22589208:T:G	donor_loss	1.0000
1:22593325:GCCCC:G	acceptor_gain	1.0000
1:22593687:G:GG	donor_gain	1.0000
1:22595226:GCAG:G	acceptor_loss	1.0000
1:22595227:CAGG:C	acceptor_loss	1.0000
1:22595228:A:AG	acceptor_gain	1.0000
1:22595228:A:T	acceptor_loss	1.0000
1:22595228:AG:A	acceptor_gain	1.0000
1:22595229:G:GG	acceptor_gain	1.0000
1:22595229:GG:G	acceptor_gain	1.0000
1:22595320:AGAGG:A	donor_loss	1.0000
1:22595321:GAG:G	donor_gain	1.0000
1:22595321:GAGGT:G	donor_loss	1.0000
1:22595324:GT:G	donor_loss	1.0000
1:22595325:T:A	donor_loss	1.0000
1:22596172:GG:G	donor_gain	1.0000
1:22596172:GGGT:G	donor_loss	1.0000
1:22596173:GG:G	donor_gain	1.0000
1:22596173:GGTG:G	donor_loss	1.0000
1:22596174:G:A	donor_loss	1.0000
1:22596174:G:GG	donor_gain	1.0000
1:22596175:TGAG:T	donor_loss	1.0000
1:22596176:GAGT:G	donor_loss	1.0000
1:22597310:A:AG	acceptor_gain	1.0000
1:22597311:G:GG	acceptor_gain	1.0000
1:22597473:TCTG:T	donor_gain	1.0000

AlphaMissense

6524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:22576219:G:C	W54C	1.000
1:22576219:G:T	W54C	1.000
1:22576308:T:C	L84P	1.000
1:22588935:G:C	W348C	1.000
1:22588935:G:T	W348C	1.000
1:22593388:T:A	W460R	1.000
1:22593388:T:C	W460R	1.000
1:22593621:G:C	R513P	1.000
1:22576217:T:A	W54R	0.999
1:22576217:T:C	W54R	0.999
1:22576274:T:A	C73S	0.999
1:22576274:T:C	C73R	0.999
1:22576275:G:A	C73Y	0.999
1:22576275:G:C	C73S	0.999
1:22576276:C:G	C73W	0.999
1:22576306:G:C	W83C	0.999
1:22576306:G:T	W83C	0.999
1:22576364:T:C	F103L	0.999
1:22576365:T:C	F103S	0.999
1:22576366:T:A	F103L	0.999
1:22576366:T:G	F103L	0.999
1:22576379:T:A	C108S	0.999
1:22576379:T:C	C108R	0.999
1:22576380:G:A	C108Y	0.999
1:22576380:G:C	C108S	0.999
1:22576380:G:T	C108F	0.999
1:22576381:C:G	C108W	0.999
1:22576409:T:A	C118S	0.999
1:22576410:G:A	C118Y	0.999
1:22576410:G:C	C118S	0.999

dbSNP variants (sampled 300 via entrez): RS1000035987 (1:22584843 C>T), RS1000052712 (1:22590089 C>T), RS1000096047 (1:22592076 G>GGATC), RS1000162452 (1:22578435 CGT>C), RS1000186841 (1:22579596 C>T), RS1000265612 (1:22572896 T>G), RS1000359882 (1:22570297 T>C), RS1000494909 (1:22600433 T>G), RS1000525307 (1:22603872 C>G), RS1000552686 (1:22584658 A>G), RS1000557121 (1:22588225 C>T), RS1000561337 (1:22565191 A>G), RS1000729363 (1:22593921 C>G), RS1000751544 (1:22575859 G>A,T), RS1000885761 (1:22563444 C>A,T)

Disease associations

OMIM: gene MIM:176945 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90011900_33	Serum alkaline phosphatase levels	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363043 (PROTEIN FAMILY), CHEMBL4134 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 623,362 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL941	IMATINIB	4	111,611
CHEMBL1908391	MASITINIB	3	2,808
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL119385	NEFLAMAPIMOD	2	1,603
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL475251	R-406	2	762
CHEMBL558752	RAF-265	2	2,721
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2
CHEMBL574738	AST-487	1

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs209709	EPHA8		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XIII RTKs: Ephrin receptor family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 66 [PMID: 19788238]	Inhibition	8.35	pIC50
RIPK3 inhibitor 18	Inhibition	7.59	pIC50
DDR1/2 inhibitor 5n	Inhibition	7.1	pKd
compound 20 [PMID: 23489211]	Inhibition	5.82	pIC50

Binding affinities (BindingDB)

13 measured of 13 human assays (13 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	KD	4500 nM

ChEMBL bioactivities

74 potent at pChembl≥5 of 75 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.62	Kd	0.24	nM	DASATINIB
8.92	IC50	1.2	nM	CHEMBL3752910
8.89	IC50	1.3	nM	DASATINIB ANHYDROUS
8.74	Kd	1.8	nM	FORETINIB
8.54	IC50	2.9	nM	CHEMBL4568087
8.35	IC50	4.5	nM	CHEMBL566515
8.23	Kd	5.9	nM	CHEMBL386051
8.05	Kd	9	nM	BOSUTINIB
7.82	Kd	15	nM	CHEMBL5415503
7.75	Kd	18	nM	AST-487
7.68	IC50	21	nM	CHEMBL4569508
7.54	IC50	29	nM	CHEMBL4550702
7.43	Kd	37	nM	NILOTINIB
7.12	IC50	75.2	nM	STAUROSPORINE
7.10	Kd	79	nM	CHEMBL4168305
7.04	Kd	91	nM	VANDETANIB
7.00	IC50	101	nM	CHEMBL5088153
6.96	IC50	109	nM	STAUROSPORINE
6.86	IC50	137	nM	STAUROSPORINE
6.85	Kd	140	nM	DORAMAPIMOD
6.80	Kd	160	nM	VANDETANIB
6.72	Kd	190	nM	STAUROSPORINE
6.68	IC50	210.4	nM	CHEMBL5653589
6.63	IC50	233	nM	CHEMBL4281823
6.60	Kd	250	nM	CHEMBL1241674
6.57	Kd	270	nM	DORAMAPIMOD
6.55	Kd	280	nM	CRIZOTINIB
6.52	Kd	300	nM	STAUROSPORINE
6.40	Kd	400	nM	PELITINIB
6.36	IC50	434	nM	CHEMBL1916891
6.30	Kd	500	nM	TOZASERTIB
6.26	Kd	550	nM	CHEMBL4553037
6.25	Kd	560	nM	CHEMBL311959
6.10	Kd	790	nM	CANERTINIB
6.03	Kd	940	nM	ERLOTINIB
6.02	Kd	960	nM	SORAFENIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	CHEMBL535429
5.96	Kd	1100	nM	RAF-265
5.89	Kd	1300	nM	R-406
5.85	Kd	1400	nM	IMATINIB
5.82	IC50	1500	nM	CHEMBL2322989
5.80	Kd	1565	nM	CHEMBL4465866
5.75	Kd	1800	nM	GEFITINIB
5.75	Kd	1800	nM	MASITINIB
5.70	Kd	2000	nM	CANERTINIB
5.68	Kd	2100	nM	IMATINIB
5.62	Kd	2400	nM	SORAFENIB

PubChem BioAssay actives

70 with measured affinity, of 718 total; 45 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
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435287: Binding constant for EPHA8 kinase domain	kd	0.0002	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147746: Inhibition of Nano Luc-fused full length C-terminal EPHA8 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.0012	uM
Dasatinib	2147746: Inhibition of Nano Luc-fused full length C-terminal EPHA8 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.0013	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625120: Binding constant for EPHA8 kinase domain	kd	0.0018	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637074: Inhibition of recombinant human GST-tagged cytoplasmic EPHA8 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0029	uM
7-(5-hydroxy-2-methylphenyl)-6-(2-methoxyphenyl)-4-methylpurino[7,8-a]imidazole-1,3-dione	441391: Inhibition of EphA8 by [gamma33-P]ATP based assay	ic50	0.0045	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625120: Binding constant for EPHA8 kinase domain	kd	0.0059	uM
Bosutinib	625120: Binding constant for EPHA8 kinase domain	kd	0.0090	uM
N-[3-[2-[2-ethoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxo-8-[[(2R)-oxolan-2-yl]methyl]pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-(trifluoromethyl)benzamide	1988535: Binding affinity to EPHA8 (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0150	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435287: Binding constant for EPHA8 kinase domain	kd	0.0180	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637074: Inhibition of recombinant human GST-tagged cytoplasmic EPHA8 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0210	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637074: Inhibition of recombinant human GST-tagged cytoplasmic EPHA8 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0290	uM
Nilotinib	625120: Binding constant for EPHA8 kinase domain	kd	0.0370	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715362: Inhibition of human EPHA8 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0752	uM
3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-ylbenzamide	1356733: Binding affinity to human EPHA8	kd	0.0790	uM
Vandetanib	435287: Binding constant for EPHA8 kinase domain	kd	0.0910	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822455: Inhibition of human EphA8 in presence of ATP by radiometric assay	ic50	0.1010	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	256600: Average Binding Constant for EPHA8; NA=Not Active at 10 uM	kd	0.1400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147746: Inhibition of Nano Luc-fused full length C-terminal EPHA8 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.2104	uM
1-[5-(4-amino-7-ethylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethoxy)phenyl]ethanone	1415176: Inhibition of recombinant human EphA8 (615 to 911 residues) using KTFCGTPEYLAPE as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis	ic50	0.2330	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625120: Binding constant for EPHA8 kinase domain	kd	0.2500	uM
Crizotinib	625120: Binding constant for EPHA8 kinase domain	kd	0.2800	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256600: Average Binding Constant for EPHA8; NA=Not Active at 10 uM	kd	0.4000	uM
(E)-4-(dimethylamino)-N-[7-fluoro-4-(2-methylanilino)imidazo[1,5-a]quinoxalin-8-yl]-N-methylbut-2-enamide	629931: Inhibition of EPHA8 relative to control	ic50	0.4340	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435287: Binding constant for EPHA8 kinase domain	kd	0.5000	uM
(4R)-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide	1625888: Binding affinity to wild type human partial length EPHA8 (608 to 920 residues) expressed in bacterial expression system preincubated for 1 hr measured after 30 mins by qPCR method	kd	0.5500	uM
6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine	1673295: Binding affinity to human wild type partial length EphA8 (Q608 to C920 residues) expressed in bacterial expression system by Kinomescan method	kd	0.5600	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	256600: Average Binding Constant for EPHA8; NA=Not Active at 10 uM	kd	0.7900	uM
Erlotinib	435287: Binding constant for EPHA8 kinase domain	kd	0.9400	uM
Sorafenib	256600: Average Binding Constant for EPHA8; NA=Not Active at 10 uM	kd	0.9600	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	435287: Binding constant for EPHA8 kinase domain	kd	1.1000	uM
6-(trifluoromethyl)-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine	1673295: Binding affinity to human wild type partial length EphA8 (Q608 to C920 residues) expressed in bacterial expression system by Kinomescan method	kd	1.1000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625120: Binding constant for EPHA8 kinase domain	kd	1.3000	uM
Imatinib	435287: Binding constant for EPHA8 kinase domain	kd	1.4000	uM
(2S)-2-[[(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	728712: Displacement of ephrin-A1-Fc from EphA8 receptor Fc ectodomain (unknown origin) after 1 hr by ELISA	ic50	1.5000	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526145: Binding affinity to recombinant N-terminal His-FLAG-GST-tagged EPHB8 (unknown origin) (571 to 924 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	1.5650	uM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide	625120: Binding constant for EPHA8 kinase domain	kd	1.8000	uM
Gefitinib	435287: Binding constant for EPHA8 kinase domain	kd	1.8000	uM
(2S)-2-[[(4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1260966: Displacement of biotinylated ephrin-A1-Fc from EphA8 (unknown origin) preincubated for 1 hr followed by biotinylated-ephrin-A1-Fc addition measured after 4 hrs by ELISA	ic50	3.1000	uM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	256600: Average Binding Constant for EPHA8; NA=Not Active at 10 uM	kd	3.1000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625120: Binding constant for EPHA8 kinase domain	kd	3.9000	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	625120: Binding constant for EPHA8 kinase domain	kd	3.9000	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	625120: Binding constant for EPHA8 kinase domain	kd	5.3000	uM
Fedratinib	625120: Binding constant for EPHA8 kinase domain	kd	7.7000	uM
2-anilino-7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1336067: Inhibition of human recombinant GST-tagged EPHA8 cytoplasmic domain (565 to 1005 residues) expressed in baculovirus expression system	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
entinostat	increases expression, affects cotreatment	2
bisphenol F	affects cotreatment, increases methylation	1
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
ponatinib	decreases activity	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldrin	affects cotreatment, increases expression	1
Arsenic	increases methylation	1
Atrazine	increases expression	1
Hexachlorocyclohexane	increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Copper	decreases expression, affects cotreatment	1
Dichlorodiphenyldichloroethane	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	affects cotreatment, increases expression	1
DDT	affects cotreatment, increases expression	1
Dieldrin	affects cotreatment, increases expression	1
Endrin	increases expression, affects cotreatment	1
Hydralazine	increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1

ChEMBL screening assays

229 unique, capped per target: 229 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024916	Binding	Binding affinity to human EPHA8 at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem

Clinical trials (associated diseases)

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