EPHA5

Summary

EPHA5 (EPH receptor A5, HGNC:3389) is a protein-coding gene on chromosome 4q13.1-q13.2, encoding Ephrin type-A receptor 5 (P54756). 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 belongs to 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. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 2044 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 145 total
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001281766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3389
Approved symbol	EPHA5
Name	EPH receptor A5
Location	4q13.1-q13.2
Locus type	gene with protein product
Status	Approved
Aliases	Hek7, TYRO4, CEK7, EHK1
Ensembl gene	ENSG00000145242
Ensembl biotype	protein_coding
OMIM	600004
Entrez	2044

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000273854, ENST00000354839, ENST00000432638, ENST00000511294, ENST00000613740, ENST00000622150, ENST00000893304

RefSeq mRNA: 6 — MANE Select: NM_001281766 NM_001281765, NM_001281766, NM_001281767, NM_001318761, NM_004439, NM_182472

CCDS: CCDS3513, CCDS3514, CCDS75131, CCDS75132, CCDS75133

Canonical transcript exons

ENST00000613740 — 17 exons

Exon	Start	End
ENSE00000969520	65367357	65367424
ENSE00000969521	65365932	65366057
ENSE00000969522	65365017	65365202
ENSE00000969523	65353042	65353103
ENSE00000969524	65351389	65351598
ENSE00000969526	65335932	65336125
ENSE00000969527	65331973	65332128
ENSE00001139187	65601641	65602304
ENSE00001139193	65643363	65643427
ENSE00001139204	65490377	65490712
ENSE00001139210	65495388	65495543
ENSE00001139288	65414284	65414443
ENSE00001139296	65420441	65420565
ENSE00001631595	65348054	65348203
ENSE00002083906	65404374	65404479
ENSE00003911482	65669562	65670489
ENSE00003913578	65319567	65324219

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 95.90.

FANTOM5 (CAGE): breadth broad, TPM avg 19.5064 / max 2051.2405, expressed in 750 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52291	7.9445	593
52292	7.4230	616
52293	1.6087	363
52290	1.5881	318
52289	0.5506	216
52294	0.1484	66
52287	0.0998	54
52296	0.0563	22
52297	0.0440	20
52295	0.0269	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.90	gold quality
ganglionic eminence	UBERON:0004023	95.35	gold quality
ventricular zone	UBERON:0003053	90.80	gold quality
sperm	CL:0000019	82.24	silver quality
prefrontal cortex	UBERON:0000451	80.98	gold quality
male germ cell	CL:0000015	79.54	silver quality
embryo	UBERON:0000922	77.51	gold quality
middle temporal gyrus	UBERON:0002771	75.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.52	gold quality
entorhinal cortex	UBERON:0002728	74.68	gold quality
frontal cortex	UBERON:0001870	74.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.61	gold quality
neocortex	UBERON:0001950	74.60	gold quality
cerebral cortex	UBERON:0000956	74.39	gold quality
primary visual cortex	UBERON:0002436	74.19	gold quality
frontal pole	UBERON:0002795	73.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.95	gold quality
stromal cell of endometrium	CL:0002255	72.89	gold quality
Ammon’s horn	UBERON:0001954	72.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	72.26	gold quality
occipital lobe	UBERON:0002021	72.11	gold quality
cingulate cortex	UBERON:0003027	71.45	gold quality
anterior cingulate cortex	UBERON:0009835	71.33	gold quality
superior frontal gyrus	UBERON:0002661	71.31	gold quality
orbitofrontal cortex	UBERON:0004167	70.51	silver quality
temporal lobe	UBERON:0001871	70.45	gold quality
postcentral gyrus	UBERON:0002581	68.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	68.28	gold quality
parietal lobe	UBERON:0001872	68.25	gold quality
amygdala	UBERON:0001876	68.22	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	472.20
E-HCAD-35	yes	57.86
E-CURD-11	yes	28.20
E-ANND-3	yes	5.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFIA, NFIB, NFIX, OLIG2, ZBED1

miRNA regulators (miRDB)

265 targeting EPHA5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-511-3P	99.99	68.85	1467
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-3667-3P	99.99	67.17	1636
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Literature-anchored findings (GeneRIF, showing 21)

• increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive ovarian cancer phenotype (PMID:16737551)
• EphA5 might be a potential target for epigenetic silencing in primary breast cancer and a valuable molecular marker for breast cancer carcinogenesis and progression. (PMID:19733895)
• Eph-A5 and Eph-A7 staining intensity was identified as independent prognostic factors for pancreatic ductal adenocarcinoma (PMID:19949912)
• these data suggest that miR-34a is a negative modulator of chondrogenesis, particularly in migration of chondroblasts, by targeting EphA5 and resulting inhibition of cellular condensation during chondrogenesis of chick limb mesenchymal cells. (PMID:22079638)
• Insertional translocation leading to a 4q13 duplication including the EPHA5 gene is associated with attention-deficit. hyperactivity disorder (PMID:23824631)
• These results indicate that EphA5 may be a negative regulator of bone formation. (PMID:24029132)
• unbound EphA5 LBD appears to comprise an ensemble of open conformations that have only small variations over the loops and appear ready to bind ephrin-A ligands (PMID:24086308)
• Our study provides evidence that EphA5 is a potential target for epigenetic silencing in primary prostate cancer and is a potentially valuable prognosis predictor and thereapeutic marker for prostate cancer. (PMID:25609195)
• demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications (PMID:25623065)
• 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)
• Our data indicate that EphA5 receptor may be a tumor suppressor in colorectal carcinoma and it may be a new therapeutic target for colorectal carcinoma. (PMID:27651378)
• Our results show that EphA5 may be a potential biomarker for distinguishing high-and low-grade ovarian serous carcinoma and a potential prognostic marker. (PMID:27887627)
• the interactions of EphA5/ephrinA5 and/or EphA7/ephrinA5 between HSPCs and BMSCs, independently and cooperatively, play a role in HSPC colony formation through the upregulation of GM-CSFR. Furthermore, the adhesion/migration of HSPCs appears to be mediated in part through the activation of Rac1. (PMID:27988259)
• EphA5 protein was negatively (0) or weakly (1+) expressed in 48 of 78 (61.5%), moderately (2+) expressed in 15 of 78 (19.2%) and strongly (3+) expressed in 15 of 78 (19.2%) tumour samples of clear cell renal cell carcinoma (ccRCC). Decreased expression of EphA5 was detected more often in females than in males (PMID:28421649)
• Genetic variation in EPHA contributes to sensitivity to paclitaxel-induced peripheral neuropathy. (PMID:31823378)
• EPHA5 mutation impairs natural killer cell-mediated cytotoxicity against non-small lung cancer cells and promotes cancer cell migration and invasion. (PMID:32234341)
• EPHA5 mutations predict survival after immunotherapy in lung adenocarcinoma. (PMID:33288738)
• Deep learning model reveals potential risk genes for ADHD, especially Ephrin receptor gene EPHA5. (PMID:34109382)
• Expression of EPHA5 in lung adenocarcinoma is associated with lymph node metastasis and EGFR mutation. (PMID:35332588)
• Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer. (PMID:36164608)
• Immunohistochemical evaluation of forkhead box A1 and EphA5 markers in serous ovarian carcinomas, and their impact on the clinical outcome of patients. (PMID:36345952)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epha5	ENSMUSG00000029245
rattus_norvegicus	Epha5	ENSRNOG00000002024

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), 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), 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 5 — P54756 (reviewed: P54756)

Alternative names: Brain-specific kinase, EPH homology kinase 1, EPH-like kinase 7

All UniProt accessions (6): A0A384MU00, B7ZKJ3, B7ZKW7, P54756, F8VP57, F8W9W0

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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.

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. Interacts (via SAM domain) with SAMD5 (via SAM domain).

Subcellular location. Cell membrane. Cell projection. Axon. Dendrite.

Tissue specificity. Almost exclusively expressed in the nervous system in cortical neurons, cerebellar Purkinje cells and pyramidal neurons within the cortex and hippocampus. Display an increasing gradient of expression from the forebrain to hindbrain and spinal cord.

Post-translational modifications. Phosphorylated. Phosphorylation is stimulated by the ligand EFNA5. Dephosphorylation upon stimulation by glucose, inhibits EPHA5 forward signaling and results in insulin secretion.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P54756-1	1	yes
P54756-2	2
P54756-3	3

RefSeq proteins (6): NP_001268694, NP_001268695, NP_001268696, NP_001305690, NP_004430, NP_872272 (=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
IPR034277	EphA5_rcpt_lig-bd	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 (84 total): strand 20, helix 15, sequence variant 12, glycosylation site 6, sequence conflict 6, domain 5, modified residue 4, splice variant 3, turn 3, binding site 2, topological domain 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2R2P	X-RAY DIFFRACTION	2.4
4ET7	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54756-F1	80.10	0.48

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): 800 (proton acceptor)

Ligand- & substrate-binding residues (2): 681–689; 707

Post-translational modifications (4): 650, 656, 833, 982

Glycosylation sites (6): 264, 299, 369, 423, 436, 461

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: 294 (showing top): GOBP_NEURON_RECOGNITION, BENPORATH_ES_WITH_H3K27ME3, GOCC_SECRETORY_GRANULE, GOBP_INSULIN_SECRETION, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (11): axon guidance (GO:0007411), hippocampus development (GO:0021766), obsolete positive regulation of CREB transcription factor activity (GO:0032793), regulation of actin cytoskeleton organization (GO:0032956), regulation of GTPase activity (GO:0043087), ephrin receptor signaling pathway (GO:0048013), neuron development (GO:0048666), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), protein phosphorylation (GO:0006468), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), nervous system development (GO:0007399)

GO Molecular Function (11): ephrin receptor activity (GO:0005003), GPI-linked ephrin receptor activity (GO:0005004), transmembrane-ephrin receptor activity (GO:0005005), ATP binding (GO:0005524), 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 (9): rough endoplasmic reticulum (GO:0005791), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), axon (GO:0030424), dendrite (GO:0030425), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), 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
cellular anatomical structure	3
ephrin receptor activity	2
neuron projection	2
axonogenesis	1
neuron projection guidance	1
pallium development	1
limbic system development	1
anatomical structure development	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
GTPase activity	1
regulation of hydrolase activity	1
cell surface receptor protein tyrosine kinase signaling pathway	1
neuron differentiation	1
cell development	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion	1
regulation of cellular localization	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
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
catalytic activity	1
endoplasmic reticulum	1
membrane	1

Protein interactions and networks

STRING

2366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHA5	EFNA5	P52803	996
EPHA5	EFNA3	P52797	954
EPHA5	EFNA2	O43921	951
EPHA5	EFNA1	P20827	946
EPHA5	EFNA4	P52798	776
EPHA5	EPHA3	P29320	758
EPHA5	EFNB2	P52799	722
EPHA5	EFNB3	Q15768	681
EPHA5	ABL1	P00519	633
EPHA5	EPHA4	P54764	596
EPHA5	EFNB1	P98172	572
EPHA5	KIRREL2	Q6UWL6	536
EPHA5	CFB	P00751	526
EPHA5	FGD4	Q96M96	496
EPHA5	KIRREL3	Q8IZU9	472

IntAct

39 interactions, top by confidence:

A	B	Type	Score
EPHA5	EPHA2	psi-mi:“MI:0915”(physical association)	0.540
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
EPHA5	EPHB4	psi-mi:“MI:0915”(physical association)	0.500
EPHA5		psi-mi:“MI:0217”(phosphorylation reaction)	0.440
EPHA5	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
	SGK1	psi-mi:“MI:0914”(association)	0.350
TRAF2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
PAK2	CS	psi-mi:“MI:0914”(association)	0.350
EPHA3	FHAD1	psi-mi:“MI:0914”(association)	0.350
EPHA5	SCO2	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
EFNA5	NBAS	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (161): EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), DUSP21 (Two-hybrid), STAT3 (Affinity Capture-Western), EPHA5 (PCA), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS)

ESM2 similar proteins: A0JM20, F1LW30, O73875, O73878, P00545, P07333, P11362, P13369, P16092, P18460, P21709, P21803, P21804, P22182, P22455, P22607, P29317, P54755, P54756, P54757, P54759, P54761, P55144, P55146, P57097, Q03142, Q04589, Q06418, Q06806, Q12866, Q15375, Q1KL86, Q498D6, Q60629, Q60750, Q60805, Q61772, Q61851, Q6UXZ4, Q8K1S2

Diamond homologs: A0A8I3NFE2, A5PMU4, D3ZAR1, O09127, O15357, O70143, P0C6S7, P29321, P29353, P54753, P54754, P54755, P54756, P54758, P59672, P98083, Q03145, Q07498, Q09YL6, Q0IIE2, Q2I6J1, Q32PV0, Q3V1H9, Q5M824, Q5PQS4, Q5R7W7, Q5SW96, Q5TGI4, Q60629, Q61120, Q62413, Q6DD51, Q6P549, Q6P9K8, Q6S5L9, Q7Z6G8, Q801G1, Q8BIZ1, Q8C142, Q8K2A1

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
EFNA3	up-regulates	EPHA5	binding
EFNA4	up-regulates	EPHA5	binding
EFNA5	up-regulates	EPHA5	binding
EFNA1	up-regulates	EPHA5	binding
EFNA2	up-regulates	EPHA5	binding
NFIA	“up-regulates quantity”	EPHA5	“transcriptional regulation”
NFIB	“up-regulates quantity”	EPHA5	“transcriptional regulation”
NFIX	“up-regulates quantity”	EPHA5	“transcriptional regulation”
EPHA5	“up-regulates activity”	GLO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
EPH-ephrin mediated repulsion of cells	6	43.9×	1e-06
EPH-Ephrin signaling	6	33.1×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	52.9×	6e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4298 predictions. Top by Δscore:

Variant	Effect	Δscore
4:65324217:TCC:T	acceptor_gain	1.0000
4:65324218:CC:C	acceptor_gain	1.0000
4:65324218:CCC:C	acceptor_gain	1.0000
4:65324218:CCCT:C	acceptor_loss	1.0000
4:65324219:CC:C	acceptor_gain	1.0000
4:65324219:CCTGC:C	acceptor_loss	1.0000
4:65324220:C:CC	acceptor_gain	1.0000
4:65324221:T:A	acceptor_loss	1.0000
4:65331971:A:AC	donor_gain	1.0000
4:65331971:ACT:A	donor_gain	1.0000
4:65331972:C:CC	donor_gain	1.0000
4:65331972:CT:C	donor_gain	1.0000
4:65331972:CTC:C	donor_gain	1.0000
4:65332125:TACT:T	acceptor_gain	1.0000
4:65332127:CT:C	acceptor_gain	1.0000
4:65332129:C:CC	acceptor_gain	1.0000
4:65335962:C:CT	donor_gain	1.0000
4:65335963:T:TT	donor_gain	1.0000
4:65348052:A:AC	donor_gain	1.0000
4:65348052:ACAT:A	donor_gain	1.0000
4:65348053:C:CC	donor_gain	1.0000
4:65348053:CAT:C	donor_gain	1.0000
4:65348053:CATC:C	donor_gain	1.0000
4:65348202:CC:C	acceptor_gain	1.0000
4:65348203:CC:C	acceptor_gain	1.0000
4:65351383:TCTTA:T	donor_loss	1.0000
4:65351384:CTTAC:C	donor_loss	1.0000
4:65351385:TTAC:T	donor_loss	1.0000
4:65351386:TACCC:T	donor_loss	1.0000
4:65351387:A:AC	donor_gain	1.0000

AlphaMissense

6672 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:65348105:C:A	W869C	1.000
4:65348105:C:G	W869C	1.000
4:65348107:A:G	W869R	1.000
4:65348107:A:T	W869R	1.000
4:65348118:C:T	G865E	1.000
4:65348123:A:C	S863R	1.000
4:65348123:A:T	S863R	1.000
4:65348125:T:G	S863R	1.000
4:65348128:A:G	W862R	1.000
4:65348128:A:T	W862R	1.000
4:65348134:C:G	D860H	1.000
4:65348135:A:C	S859R	1.000
4:65348135:A:T	S859R	1.000
4:65348137:T:G	S859R	1.000
4:65348147:A:C	F855L	1.000
4:65348147:A:T	F855L	1.000
4:65348148:A:G	F855S	1.000
4:65348149:A:G	F855L	1.000
4:65348180:C:A	W844C	1.000
4:65348180:C:G	W844C	1.000
4:65348182:A:G	W844R	1.000
4:65348182:A:T	W844R	1.000
4:65351444:T:A	D818V	1.000
4:65351482:G:C	N805K	1.000
4:65351482:G:T	N805K	1.000
4:65351486:C:A	R804I	1.000
4:65351495:A:G	L801P	1.000
4:65351498:T:A	D800V	1.000
4:65351498:T:G	D800A	1.000
4:65351501:C:A	R799I	1.000

dbSNP variants (sampled 300 via entrez): RS10000019 (4:65342630 T>C), RS1000003122 (4:65610116 A>G), RS1000009140 (4:65623634 T>G), RS1000014614 (4:65508095 C>T), RS1000034087 (4:65542398 C>A,T), RS1000034468 (4:65494308 A>C,G), RS1000058053 (4:65581611 T>A,C), RS1000063767 (4:65354063 T>G), RS1000066000 (4:65458475 C>G,T), RS1000071117 (4:65440029 C>T), RS10000732 (4:65507662 C>A,G,T), RS1000077400 (4:65367961 G>C), RS1000078826 (4:65549343 G>A), RS1000080861 (4:65575691 G>C), RS1000081739 (4:65416150 C>A,G)

Disease associations

OMIM: gene MIM:600004 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): astrocytoma (excluding glioblastoma) (MONDO:0019781)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001352_10	HIV-1 viral setpoint	1.000000e-06
GCST002826_10	Urate levels (BMI interaction)	2.000000e-06
GCST003445_2	Response to cyclophosphamide in systemic lupus erythematosus with lupus nephritis	9.000000e-07
GCST007259_3	Severe skin toxicity response to cetuximab in colorectal cancer	4.000000e-07
GCST007325_100	General risk tolerance (MTAG)	2.000000e-10
GCST007576_128	Chronotype	3.000000e-08
GCST007576_227	Chronotype	3.000000e-08
GCST008595_46	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006319	HIV viral set point measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0007682	response to cetuximab
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001254	Astrocytoma	C04.557.465.625.600.380.080; C04.557.470.670.380.080; C04.557.580.625.600.380.080

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363043 (PROTEIN FAMILY), CHEMBL3987 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 627,510 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL119385	NEFLAMAPIMOD	2	1,603
CHEMBL1230609	FORETINIB	2
CHEMBL2029988	CEP-32496	2
CHEMBL206834	BAFETINIB	2
CHEMBL2408045	SAPITINIB	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL564829	MILCICLIB	2
CHEMBL607707	PELITINIB	2
CHEMBL203567	RO-3201195	1

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7349683	Toxicity	3	paclitaxel	Breast Neoplasms;Ovarian Neoplasms;Peripheral Nervous System Diseases

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7349683	EPHA5	3	2.00	1	paclitaxel

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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 66 [PMID: 19788238]	Inhibition	8.52	pIC50
RIPK3 inhibitor 18	Inhibition	7.85	pIC50
compound 20 [PMID: 23489211]	Inhibition	5.62	pIC50

Binding affinities (BindingDB)

7 measured of 7 human assays (7 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
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-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 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

ChEMBL bioactivities

83 potent at pChembl≥5 of 83 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
9.40	Kd	0.4	nM	CHEMBL400402
8.68	IC50	2.1	nM	DASATINIB ANHYDROUS
8.55	IC50	2.8	nM	CHEMBL3752910
8.52	Kd	3	nM	CHEMBL249097
8.52	IC50	3	nM	CHEMBL566515
8.44	Kd	3.664	nM	DASATINIB ANHYDROUS
8.43	Kd	3.7	nM	DASATINIB ANHYDROUS
8.40	Kd	4	nM	DASATINIB
8.18	Kd	6.6	nM	FORETINIB
8.10	Kd	8	nM	PONATINIB
7.99	IC50	10.3	nM	STAUROSPORINE
7.85	Kd	14	nM	CHEMBL386051
7.67	IC50	21.5	nM	STAUROSPORINE
7.64	IC50	22.96	nM	CHEMBL5423601
7.57	IC50	27.2	nM	STAUROSPORINE
7.57	Kd	27	nM	BOSUTINIB
7.42	Kd	38	nM	CHEMBL3752910
7.42	Kd	38.02	nM	CHEMBL3752910
7.20	ED50	63.31	nM	CHEMBL3752910
7.12	Kd	75	nM	CHEMBL3688339
7.09	Kd	81	nM	XL-228
7.06	Kd	88	nM	DANUSERTIB
7.05	IC50	90	nM	DORAMAPIMOD
7.02	Kd	95	nM	STAUROSPORINE
6.85	Kd	140	nM	AST-487
6.83	Kd	147	nM	MILCICLIB
6.82	Kd	150	nM	STAUROSPORINE
6.68	IC50	208.5	nM	CHEMBL5653589
6.67	Kd	214	nM	GOLVATINIB
6.66	Kd	219	nM	FORETINIB
6.62	Kd	240	nM	VANDETANIB
6.57	Kd	270	nM	CANERTINIB
6.51	Kd	310	nM	VANDETANIB
6.46	Kd	345	nM	BAFETINIB
6.44	Kd	360	nM	SORAFENIB
6.40	Kd	401	nM	CEP-32496
6.29	Kd	508	nM	TAK-901
6.23	Kd	588	nM	CHEMBL5653589
6.22	Kd	601	nM	TIVOZANIB
6.15	Kd	710	nM	PELITINIB
6.15	Kd	710	nM	ERLOTINIB
6.08	Kd	835	nM	SAPITINIB
6.07	Kd	860	nM	R-406
6.01	ED50	981.6	nM	CHEMBL5653589
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Kd	1000	nM	CRIZOTINIB
5.95	Kd	1123	nM	REGORAFENIB

PubChem BioAssay actives

77 with measured affinity, of 990 total; 49 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	435158: Binding constant for EPHA5 kinase domain	kd	0.0002	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0004	uM
Dasatinib	2147743: Inhibition of Nano Luc-fused full length C-terminal EPHA5 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.0021	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147743: Inhibition of Nano Luc-fused full length C-terminal EPHA5 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.0028	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389072: Binding affinity to human EPHA5	kd	0.0030	uM
7-(5-hydroxy-2-methylphenyl)-6-(2-methoxyphenyl)-4-methylpurino[7,8-a]imidazole-1,3-dione	441389: Inhibition of EphA5 by [gamma33-P]ATP based assay	ic50	0.0030	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	624737: Binding constant for EPHA5 kinase domain	kd	0.0066	uM
Ponatinib	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0080	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	1715367: Inhibition of human EPHA5 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0103	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624737: Binding constant for EPHA5 kinase domain	kd	0.0140	uM
N-[3-cyclopropyl-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-5-methyl-18-oxo-9-oxa-17,23,25,26-tetrazatetracyclo[17.5.2.14,8.022,25]heptacosa-1(24),4,6,8(27),19(26),20,22-heptaen-2-yne-6-carboxamide	2014045: Inhibition of EphA5 (unknown origin)	ic50	0.0230	uM
Bosutinib	624737: Binding constant for EPHA5 kinase domain	kd	0.0270	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0750	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0810	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0880	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	636425: Inhibition of EPHA5	ic50	0.0900	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435158: Binding constant for EPHA5 kinase domain	kd	0.1400	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1470	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147743: Inhibition of Nano Luc-fused full length C-terminal EPHA5 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.2085	uM
1-N’-[2-fluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2140	uM
Vandetanib	435158: Binding constant for EPHA5 kinase domain	kd	0.2400	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	256591: Average Binding Constant for EPHA5; NA=Not Active at 10 uM	kd	0.2700	uM
4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3450	uM
Sorafenib	256591: Average Binding Constant for EPHA5; NA=Not Active at 10 uM	kd	0.3600	uM
1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4010	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5080	uM
Tivozanib	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.6010	uM
Erlotinib	624737: Binding constant for EPHA5 kinase domain	kd	0.7100	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256591: Average Binding Constant for EPHA5; NA=Not Active at 10 uM	kd	0.7100	uM
2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-N-methylacetamide	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.8350	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	624737: Binding constant for EPHA5 kinase domain	kd	0.8600	uM
Crizotinib	624737: Binding constant for EPHA5 kinase domain	kd	1.0000	uM
regorafenib anhydrous	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1230	uM
Sunitinib	624737: Binding constant for EPHA5 kinase domain	kd	1.2000	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	435158: Binding constant for EPHA5 kinase domain	kd	1.4000	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	624737: Binding constant for EPHA5 kinase domain	kd	1.5000	uM
Gefitinib	624737: Binding constant for EPHA5 kinase domain	kd	1.5000	uM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	256591: Average Binding Constant for EPHA5; NA=Not Active at 10 uM	kd	1.9000	uM
Nilotinib	624737: Binding constant for EPHA5 kinase domain	kd	1.9000	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.3810	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	728716: Displacement of ephrin-A1-Fc from EphA5 receptor Fc ectodomain (unknown origin) after 1 hr by ELISA	ic50	2.4000	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	1260963: Displacement of biotinylated ephrin-A1-Fc from EphA5 (unknown origin) preincubated for 1 hr followed by biotinylated-ephrin-A1-Fc addition measured after 4 hrs by ELISA	ic50	2.6000	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624737: Binding constant for EPHA5 kinase domain	kd	3.1000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624737: Binding constant for EPHA5 kinase domain	kd	3.5000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624737: Binding constant for EPHA5 kinase domain	kd	3.7000	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	1424990: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	4.0570	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624737: Binding constant for EPHA5 kinase domain	kd	5.5000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	624737: Binding constant for EPHA5 kinase domain	kd	5.9000	uM
[5-amino-1-(4-fluorophenyl)pyrazol-4-yl]-[3-[(2S)-2,3-dihydroxypropoxy]phenyl]methanone	261337: Inhibition of EPHA5 at 10 uM	kd	6.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression, affects methylation	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
bisphenol A	increases methylation	1
lead acetate	affects cotreatment, decreases expression	1
arsenite	increases methylation	1
chromous chloride	affects cotreatment, decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
chromic oxide	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
ponatinib	decreases activity	1
Dasatinib	affects binding	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Melphalan	decreases expression	1
Phthalic Acids	decreases methylation	1
Tetrachloroethylene	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	affects cotreatment, decreases expression	1

ChEMBL screening assays

243 unique, capped per target: 243 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024908	Binding	Binding affinity to human EPHA5 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)

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

Trial	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT00154375	PHASE3	COMPLETED	Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
NCT00335075	PHASE3	COMPLETED	Efficacy and Safety of Temodal vs Semustine in Subjects With Recurrent Glioblastoma or Anaplastic Astrocytoma (Study P03644)
NCT00897377	PHASE3	TERMINATED	Treatment Strategy for Low-grade Gliomas
NCT01649830	PHASE3	RECRUITING	Efficacy of Post-radiation Adjuvant Temozolomide Chemotherapy in Residue Low-grade Glioma
NCT01655927	PHASE3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03722355	PHASE3	COMPLETED	Hyperfractionated RT With BCNU Versus Conventional RT With BCNU for Supratentorial Malignant Glioma
NCT00165360	PHASE2	COMPLETED	Prolonged Daily Temozolomide for Low-Grade Glioma
NCT00179803	PHASE2	COMPLETED	Stem Cell Transplant for High Risk Central Nervous System (CNS) Tumors
NCT00360828	PHASE2	TERMINATED	Phase II Study of Irinotecan HCI for Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas
NCT00389090	PHASE2	TERMINATED	A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
NCT00392171	PHASE2	COMPLETED	The Effects of Continuous 28-day (28/28) Temozolomide Chemotherapy in Subjects With Recurrent Malignant Glioma Who Have Failed the Conventional 5-day (5/28) Treatment (P04601)
NCT00575887	PHASE2	COMPLETED	Efficacy of Protracted Temozolomide in Patients With Progressive High Grade Glioma
NCT00782626	PHASE2	COMPLETED	Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
NCT00783393	PHASE2	COMPLETED	SCH 52365 Phase II Clinical Study: A Study on the Efficacy and Safety of Monotherapy With SCH 52365 in Patients With First Relapsed Anaplastic Astrocytoma (Study P03745)
NCT00921167	PHASE2	COMPLETED	A Study to Evaluate the Efficacy of Bevacizumab Plus Irinotecan in Recurrent Gliomas
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01351519	PHASE2	TERMINATED	A Study of Aminolevulinic Acid Used to Enhance Visualization and Surgical Removal of Brain Tumors
NCT02209428	PHASE2	UNKNOWN	A Prospective Cohort to Study the Effect of Temozolomide on IDH Mutational Low Grade Gliomas
NCT02372409	PHASE2	TERMINATED	Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors
NCT02684058	PHASE2	COMPLETED	Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
NCT03032484	PHASE2	COMPLETED	TVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma
NCT05297864	PHASE2	TERMINATED	PARP Inhibition for Gliomas (PI-4G or π4g)
NCT05345002	PHASE2	RECRUITING	All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma
NCT05683808	PHASE2	RECRUITING	Venous Thromboembolism Prevention in Outpatients With Glioma
NCT06161974	PHASE2	RECRUITING	Study of Olutasidenib and Temozolomide in HGG
NCT06439420	PHASE2	COMPLETED	CBT-I in Primary Brain Tumor Patients: Phase IIc Randomized Feasibility Pilot Trial
NCT07417761	PHASE2	RECRUITING	Tuvusertib in Astrocytoma With ATRX Mutation
NCT07439172	PHASE2	NOT_YET_RECRUITING	Pre-Radiation Chemotherapy for Newly Diagnosed High-Grade Glioma.
NCT00080054	PHASE1	COMPLETED	A Study of Motexafin Gadolinium and Temozolomide for the Treatment of Malignant Gliomas
NCT00591058	PHASE1	UNKNOWN	Safety and Dose-Finding Study of TM-601 in Adults With Recurrent Malignant Glioma
NCT00994071	PHASE1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01502605	PHASE1	TERMINATED	Phase I Study of Orally Administered Aminolevulinic Acid for Resection of Malignant Astrocytomas
NCT02010606	PHASE1	COMPLETED	Phase I Study of a Dendritic Cell Vaccine for Patients With Either Newly Diagnosed or Recurrent Glioblastoma
NCT02529072	PHASE1	COMPLETED	Nivolumab With DC Vaccines for Recurrent Brain Tumors
NCT02764151	PHASE1	TERMINATED	First in Patient Study for PF-06840003 in Malignant Gliomas
NCT03152318	PHASE1	ACTIVE_NOT_RECRUITING	A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2
NCT03911388	PHASE1	RECRUITING	HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
NCT04047303	PHASE1	TERMINATED	CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma