EPHA1

Summary

EPHA1 (EPH receptor A1, HGNC:3385) is a protein-coding gene on chromosome 7q34-q35, encoding Ephrin type-A receptor 1 (P21709). Receptor tyrosine kinase which binds promiscuously membrane-bound 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. This gene is expressed in some human cancer cell lines and has been implicated in carcinogenesis.

Source: NCBI Gene 2041 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 208 total
• Druggable target: yes — 37 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3385
Approved symbol	EPHA1
Name	EPH receptor A1
Location	7q34-q35
Locus type	gene with protein product
Status	Approved
Aliases	EPH
Ensembl gene	ENSG00000146904
Ensembl biotype	protein_coding
OMIM	179610
Entrez	2041

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 retained_intron, 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000275815, ENST00000458129, ENST00000465208, ENST00000479459, ENST00000488068, ENST00000494989, ENST00000497891, ENST00000919331

RefSeq mRNA: 1 — MANE Select: NM_005232 NM_005232

CCDS: CCDS5884

Canonical transcript exons

ENST00000275815 — 18 exons

Exon	Start	End
ENSE00000977946	143398601	143398945
ENSE00001183966	143391129	143391535
ENSE00001215599	143408724	143408856
ENSE00003465798	143399651	143400053
ENSE00003476800	143401324	143401605
ENSE00003493391	143399258	143399413
ENSE00003512731	143397920	143398070
ENSE00003552066	143395121	143395182
ENSE00003559338	143395319	143395504
ENSE00003567572	143394194	143394343
ENSE00003579557	143391620	143391775
ENSE00003589448	143397561	143397657
ENSE00003622607	143407611	143407678
ENSE00003644299	143396385	143396510
ENSE00003647550	143394808	143395014
ENSE00003670528	143398321	143398448
ENSE00003672580	143397304	143397362
ENSE00003682720	143393671	143393864

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 98.48.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3854 / max 110.6823, expressed in 531 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86673	2.6835	483
86672	1.5513	379
86671	0.1425	68
86670	0.0081	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.48	gold quality
esophagus mucosa	UBERON:0002469	95.84	gold quality
skin of leg	UBERON:0001511	92.70	gold quality
skin of abdomen	UBERON:0001416	92.04	gold quality
right uterine tube	UBERON:0001302	90.41	gold quality
right lobe of liver	UBERON:0001114	89.50	gold quality
esophagus	UBERON:0001043	88.29	gold quality
minor salivary gland	UBERON:0001830	87.78	gold quality
vagina	UBERON:0000996	87.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.73	gold quality
zone of skin	UBERON:0000014	86.49	gold quality
metanephros cortex	UBERON:0010533	85.77	gold quality
left lobe of thyroid gland	UBERON:0001120	85.13	gold quality
ectocervix	UBERON:0012249	84.96	gold quality
mucosa of transverse colon	UBERON:0004991	84.75	gold quality
transverse colon	UBERON:0001157	84.49	gold quality
right lung	UBERON:0002167	84.45	gold quality
right lobe of thyroid gland	UBERON:0001119	84.43	gold quality
body of stomach	UBERON:0001161	83.96	gold quality
upper lobe of left lung	UBERON:0008952	83.78	gold quality
gall bladder	UBERON:0002110	83.76	gold quality
body of pancreas	UBERON:0001150	83.31	gold quality
left uterine tube	UBERON:0001303	83.13	gold quality
small intestine	UBERON:0002108	82.85	gold quality
vermiform appendix	UBERON:0001154	82.79	gold quality
thyroid gland	UBERON:0002046	82.79	gold quality
body of uterus	UBERON:0009853	82.58	gold quality
mouth mucosa	UBERON:0003729	82.49	gold quality
rectum	UBERON:0001052	81.93	gold quality
granulocyte	CL:0000094	81.72	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7008	no	131.50
E-ANND-3	no	1.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

39 targeting EPHA1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4664-5P	98.17	65.07	1020

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• EphA1 seems to be a marker of the differentiated normal epidermis and its downregulation in nonmelanoma skin cancer may contribute to carcinogenesis of these very frequent human tumors. (PMID:16862074)
• Increasing ephrin-A expression enhances T-cell interactions not only with purified integrin ligands but also endothelial cells, while EphA activation down-regulates these interactions. (PMID:17980912)
• I 12 acquired a higher affinity toward EphA2 with K(d) 18 nm and inhibited vascular endothelial growth factor-dependent angiogenic invasion in a Matrigel plug assay (PMID:18308734)
• EphA2 and EphrinA-1 may play an important role in the development of a subset of early cervical cancers (PMID:18566674)
• Results suggest that EphA1-receptor transmembrane domains contribute to the dimerization-mediated receptor activation. (PMID:18590698)
• analysis of the spatial structure and pH-dependent conformational diversity of dimeric transmembrane domain of the receptor tyrosine kinase EphA1 (PMID:18728013)
• In EphA1 null transgenic mice a possible role for EphA1 in tissue patterning and hormone-induced apoptotic processes is indicated. (PMID:18802966)
• We report selective targeting of PC-3 cells with nanoshells conjugated to ephrinA I, a ligand for EphA2 receptor that is overexpressed on PC-3 cells. (PMID:18990944)
• EphA1 may play different roles during the different stages of colorectal carcinoma progression. (PMID:19011600)
• EphA1 regulates cell morphology and motility through the ILK-RhoA-ROCK pathway. (PMID:19118217)
• Epigenetic silencing of EphA1 expression in colorectal cancer is correlated with poor survival. (PMID:19277044)
• The crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2, are presented. (PMID:19525919)
• Eph-A1 staining intensity was significantly associated with tumor size and tumor histopathological stage in pancreatic ductal adenocarcinoma (PMID:19949912)
• Suppression of EphA1 expression in Huh-7 cells reduced their outgrowth when inoculated in the subcutaneous space in the flank of nude mice, presumably through angiogenesis inhibition since microvessel density was found to be inhibited. (PMID:20043122)
• The EphA1 expression level is a potential prognostic marker in gastric carcinoma, and may provide a novel target of therapy for gastric carcinoma. (PMID:21042754)
• found independent evidence for association for Alzheimer’s disease susceptibility loci at EPHA1, CD33 and CD2AP (PMID:21460840)
• Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. (PMID:21460841)
• The present study reveals a novel function for EphA1 and EphB2 in the induction of autophagy, suggesting a tumor suppressor role for these proteins in colorectal cancer. (PMID:21503576)
• Ephrin-A1 activates EphA2 on the surface of MDA-MB-231 human breast cancer cells. (PMID:22261062)
• analysis of structural and functional characterization of monomeric EphrinA1 binding site to EphA2 receptor (PMID:22362770)
• EphrinA1 is released in three forms from cancer cells by matrix metalloproteases (PMID:22688511)
• Results show that EphA1 appears to be a differentiation marker for esophageal squamous cells, and its increased expression is positively associated with lymph node metastasis and advanced disease stage. (PMID:23030051)
• High Eph A1 expression is associated with choriocarcinoma invasion. (PMID:23429488)
• Suggest EphA1 receptor may have roles in carcinogenesis and progression of prostate cancer. (PMID:24040450)
• Lack of ephrin receptor A1 is a favorable independent prognostic factor in clear cell renal cell carcinoma. (PMID:25025847)
• This study suggests EPHA1 (rs11771145) interferes with the pathological alteration of the hippocampus and the lateral occipitotemporal and inferior temporal gyri throughout the Alzheimer’s disease process, leading to a lower risk of Alzheimer’s disease. (PMID:25182741)
• two states of the EphA1 transmembrane helix dimer (PMID:25286141)
• High expression of EphA1 was associated with metastasis and recurrence in Gastric Cancer. (PMID:25391265)
• EphrinA1 plays an important role in the TNF-alpha-mediated adhesion of monocytes to endothelial cells. (PMID:25451169)
• Data indicate that EphA1 protein may be a new marker for the prognosis of clear cell renal cell carcinoma. (PMID:26261568)
• EPHA1 suppresses spreading and adhesion of HRT18 colorectal cancer cells through deactivation of ERK and JNK signaling pathways. (PMID:26977017)
• Data show that Ephrin B3 was concomitantly expressed with EphA2 and Ephrin A1 with higher Ephrin B3 levels found in non-squamous than in squamous tumors. (PMID:27533087)
• Results show that EPHA1 expression is up-regulated in ovarian cancer (OC) cells and provide evidence that it may promote the aggression of some OC cells. (PMID:28739735)
• The rs11767557 variant could significantly regulate EPHA1 gene expression specifically in human whole blood. These findings may further provide important supplementary information about the regulating mechanisms of rs11767557 variant in Alzheimer’s disease risk. (PMID:29332039)
• EphA1 expression is decreased in ovarian serous carcinoma compared with normal fallopian tube and benign ovarian serous cystadenoma. Decreased EphA1 expression was more often detected in high-grade tumors. (PMID:29393455)
• High erythropoietin-producing hepatocellular carcinoma receptor A (EphA) 1, 2, and 4 expression levels were significantly related to recurrence. (PMID:29491103)
• EphB1 and EphA1 phosphorylate the Cx32CT domain residue Tyr(243) Unlike for Cx43, the tyrosine phosphorylation of the Cx32CT increased gap junction intercellular communication. (PMID:30401746)
• ABCA7 and EphA1 Genes Polymorphisms in Late-Onset Alzheimer’s Disease. (PMID:31659653)
• Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance. (PMID:32218416)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epha1	ENSMUSG00000029859
rattus_norvegicus	Epha1	ENSRNOG00000017525

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), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), 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 1 — P21709 (reviewed: P21709)

Alternative names: EPH tyrosine kinase, EPH tyrosine kinase 1, Erythropoietin-producing hepatoma receptor, Tyrosine-protein kinase receptor EPH

All UniProt accessions (1): P21709

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase which binds promiscuously membrane-bound 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. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.

Subunit / interactions. Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts (kinase activity-dependent) with PTK2/FAK1.

Subcellular location. Cell membrane.

Tissue specificity. Overexpressed in several carcinomas.

Post-translational modifications. Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1. Ubiquitinated.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P21709-1	1	yes
P21709-2	2
P21709-3	3

RefSeq proteins (1): NP_005223* (*=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
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011641	Tyr-kin_ephrin_A/B_rcpt-like	Domain
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
IPR034251	EphA1_rcpt_lig-bd	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050449	Ephrin_rcpt_TKs	Family

Pfam: PF00041, PF00536, PF01404, PF07699, 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 (43 total): sequence variant 9, helix 7, modified residue 6, domain 5, splice variant 4, binding site 2, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, active site 1, glycosylation site 1, transmembrane region 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3HIL	X-RAY DIFFRACTION	2
3KKA	X-RAY DIFFRACTION	2.4
2K1K	SOLUTION NMR
2K1L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21709-F1	80.74	0.38

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): 749 (proton acceptor)

Ligand- & substrate-binding residues (2): 630–638; 656

Post-translational modifications (6): 599, 605, 781, 906, 910, 930

Glycosylation sites (1): 414

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-3928665	EPH-ephrin mediated repulsion of cells

MSigDB gene sets: 212 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_POSITIVE_REGULATION_OF_CELL_MATRIX_ADHESION, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (12): angiogenesis (GO:0001525), positive regulation of cell-matrix adhesion (GO:0001954), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of cell migration (GO:0030335), negative regulation of cell migration (GO:0030336), substrate adhesion-dependent cell spreading (GO:0034446), positive regulation of angiogenesis (GO:0045766), positive regulation of stress fiber assembly (GO:0051496), protein phosphorylation (GO:0006468), cell adhesion (GO:0007155), regulation of cell adhesion (GO:0030155), ephrin receptor signaling pathway (GO:0048013)

GO Molecular Function (12): fibronectin binding (GO:0001968), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ephrin receptor activity (GO:0005003), transmembrane-ephrin receptor activity (GO:0005005), ATP binding (GO:0005524), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
EPH-Ephrin signaling	2
Axon guidance	1
Transcriptional regulation of pluripotent stem cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
regulation of cell migration	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
enzyme-linked receptor protein signaling pathway	1
positive regulation of cell motility	1
negative regulation of cell motility	1
cell-substrate adhesion	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
phosphorylation	1
protein modification process	1
cellular process	1
cell adhesion	1
regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
protein binding	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
transmembrane receptor protein tyrosine kinase activity	1
ephrin receptor signaling pathway	1
ephrin receptor activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase 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
binding	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

2598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHA1	EFNA1	P20827	999
EPHA1	EFNB2	P52799	998
EPHA1	EFNB1	P98172	997
EPHA1	EFNA2	O43921	997
EPHA1	EFNA3	P52797	997
EPHA1	EFNA4	P52798	995
EPHA1	EFNA5	P52803	995
EPHA1	EFNB3	Q15768	986
EPHA1	NGEF	Q8N5V2	880
EPHA1	PICALM	Q13492	846
EPHA1	JAG1	P78504	811
EPHA1	EPHA2	P29317	795
EPHA1	ABCA7	Q8IZY2	777
EPHA1	CD2AP	Q9Y5K6	767
EPHA1	FN1	P02751	746

IntAct

79 interactions, top by confidence:

A	B	Type	Score
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
EPHA2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
PVR	ORC4	psi-mi:“MI:0914”(association)	0.530
EPHA1		psi-mi:“MI:0915”(physical association)	0.500
INPPL1	EPHA1	psi-mi:“MI:0407”(direct interaction)	0.440
EPHA1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
	EPHA1	psi-mi:“MI:0407”(direct interaction)	0.440
EPHA1	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Fer	EPHA1	psi-mi:“MI:0915”(physical association)	0.400
EPHA1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
CTDSP2	EPHA1	psi-mi:“MI:0915”(physical association)	0.370
PTPN11	EPHA1	psi-mi:“MI:0915”(physical association)	0.370
DUSP14	EPHA1	psi-mi:“MI:0915”(physical association)	0.370
TPTE	EPHA1	psi-mi:“MI:0915”(physical association)	0.370
MTMR14	EPHA1	psi-mi:“MI:0915”(physical association)	0.370
EPHA1	MYO1B	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PCDHA8	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SGCA	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASPH	POTEF	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
CEACAM21	GAPDHS	psi-mi:“MI:0914”(association)	0.350

BioGRID (298): EPHA1 (Biochemical Activity), EPHA1 (Biochemical Activity), SMG1 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), USP34 (Affinity Capture-MS), SMG9 (Affinity Capture-MS), FAM114A2 (Affinity Capture-MS), DYNC2H1 (Affinity Capture-MS), DIAPH3 (Affinity Capture-MS), DFNA5 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), WDR13 (Affinity Capture-MS), ARMC9 (Affinity Capture-MS), STK17B (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS)

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: A0JNB0, A1Y2K1, A2VDU3, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, F4JTP5, H2KZW3, O01700, O08680, O13146, O13148, O22558, O42422, O43283, O43318, O73878, P00523, P00524, P00525, P00526, P05480, P09759, P0C8E4, P12931, P13115, P13116, P13406, P14085, P15054, P15209, P21709, P27446, P28693, P29318, P29319, P29320, P29323

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EFNA1	up-regulates	EPHA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Synthesis of PIPs at the plasma membrane	5	16.5×	2e-03
VEGFA-VEGFR2 Pathway	5	10.9×	4e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	7.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	160
Likely benign	15
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2822 predictions. Top by Δscore:

Variant	Effect	Δscore
7:143391618:A:AC	donor_gain	1.0000
7:143391619:C:CC	donor_gain	1.0000
7:143391619:CT:C	donor_gain	1.0000
7:143391619:CTCAG:C	donor_gain	1.0000
7:143391623:G:C	donor_gain	1.0000
7:143391771:TCATC:T	acceptor_gain	1.0000
7:143391772:CATC:C	acceptor_gain	1.0000
7:143391772:CATCC:C	acceptor_gain	1.0000
7:143391773:ATC:A	acceptor_gain	1.0000
7:143391774:TC:T	acceptor_gain	1.0000
7:143391774:TCCT:T	acceptor_loss	1.0000
7:143391775:CC:C	acceptor_gain	1.0000
7:143391776:C:CC	acceptor_gain	1.0000
7:143391776:CTGTG:C	acceptor_loss	1.0000
7:143391777:T:G	acceptor_loss	1.0000
7:143393666:GTTAC:G	donor_loss	1.0000
7:143393667:TTA:T	donor_loss	1.0000
7:143393668:TA:T	donor_loss	1.0000
7:143393669:ACC:A	donor_loss	1.0000
7:143393670:C:A	donor_loss	1.0000
7:143393862:AACC:A	acceptor_loss	1.0000
7:143393865:CTGC:C	acceptor_loss	1.0000
7:143394188:GCTCA:G	donor_loss	1.0000
7:143394189:CTCAC:C	donor_loss	1.0000
7:143394190:TCA:T	donor_loss	1.0000
7:143394191:CA:C	donor_loss	1.0000
7:143394192:ACCT:A	donor_gain	1.0000
7:143394193:C:A	donor_loss	1.0000
7:143394193:CCTC:C	donor_gain	1.0000
7:143394195:T:TA	donor_gain	1.0000

AlphaMissense

6318 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:143391711:A:G	W921R	0.999
7:143391711:A:T	W921R	0.999
7:143394268:A:G	W810R	0.999
7:143394268:A:T	W810R	0.999
7:143394275:G:C	S807R	0.999
7:143394275:G:T	S807R	0.999
7:143394277:T:G	S807R	0.999
7:143394322:A:G	W792R	0.999
7:143394322:A:T	W792R	0.999
7:143391707:A:G	L922P	0.998
7:143391707:A:T	L922H	0.998
7:143394247:A:G	W817R	0.998
7:143394247:A:T	W817R	0.998
7:143394259:C:A	G813W	0.998
7:143394263:G:C	S811R	0.998
7:143394263:G:T	S811R	0.998
7:143394265:T:G	S811R	0.998
7:143394320:C:A	W792C	0.998
7:143394320:C:G	W792C	0.998
7:143394917:C:G	R748P	0.998
7:143395434:C:A	K656N	0.998
7:143395434:C:G	K656N	0.998
7:143391488:A:G	I967T	0.997
7:143391709:C:A	W921C	0.997
7:143391709:C:G	W921C	0.997
7:143394245:C:A	W817C	0.997
7:143394245:C:G	W817C	0.997
7:143394258:C:T	G813E	0.997
7:143394898:G:C	N754K	0.997
7:143394898:G:T	N754K	0.997

dbSNP variants (sampled 300 via entrez): RS1000056958 (7:143401247 G>C), RS1000282912 (7:143392928 C>T), RS1000399540 (7:143400786 T>G), RS1000411029 (7:143392736 G>C,T), RS1000430761 (7:143401101 C>T), RS1000636068 (7:143407656 C>G,T), RS1000673503 (7:143397247 A>G), RS1000688605 (7:143404430 G>C,T), RS1000739419 (7:143402482 A>G), RS1000926968 (7:143402358 T>C), RS1000994877 (7:143409022 G>A,C), RS1001039742 (7:143409888 CG>C), RS1001150031 (7:143409477 G>A,C,T), RS1001279360 (7:143397091 T>TG), RS1001425150 (7:143408483 G>A,T)

Disease associations

OMIM: gene MIM:179610 | disease phenotypes: MIM:600057

GenCC curated gene-disease

Mondo (1): bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039)

Orphanet (1): Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001026_9	Alzheimer’s disease (late onset)	6.000000e-10
GCST002245_8	Alzheimer’s disease (late onset)	1.000000e-13
GCST002817_10	Alzheimer’s disease in APOE e4- carriers	8.000000e-06
GCST006585_89	Blood protein levels	2.000000e-223
GCST007319_33	Alzheimer’s disease (late onset)	4.000000e-08
GCST007319_9	Alzheimer’s disease (late onset)	3.000000e-11
GCST007320_102	Alzheimer’s disease or family history of Alzheimer’s disease	1.000000e-06
GCST007320_8	Alzheimer’s disease or family history of Alzheimer’s disease	4.000000e-11
GCST007321_22	Family history of Alzheimer’s disease	1.000000e-06
GCST007827_20	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-10
GCST009021_6	Alzheimer’s disease	5.000000e-10
GCST90012877_24	Alzheimer’s disease or family history of Alzheimer’s disease	1.000000e-11
GCST90012877_25	Alzheimer’s disease or family history of Alzheimer’s disease	3.000000e-10
GCST90013407_83	Liver enzyme levels (gamma-glutamyl transferase)	4.000000e-27

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009268	family history of Alzheimer’s disease
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363043 (PROTEIN FAMILY), CHEMBL5810 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

37 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 472,537 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL119385	NEFLAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1738757	REBASTINIB	2
CHEMBL2408045	SAPITINIB	2
CHEMBL3979920	MIVAVOTINIB	2
CHEMBL3991932	PEXMETINIB	2
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2

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

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 66 [PMID: 19788238]	Inhibition	8.54	pIC50
compound 20 [PMID: 23489211]	Inhibition	5.64	pIC50

Binding affinities (BindingDB)

9 measured of 10 human assays (10 total across all organisms); most potent 9 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-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 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
CI-1033	KD	1700 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer

ChEMBL bioactivities

95 potent at pChembl≥5 of 99 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.54	IC50	2.9	nM	CHEMBL566515
8.39	Kd	4.1	nM	DASATINIB
8.30	Kd	5	nM	XL-228
8.30	Kd	5	nM	CHEMBL249097
8.21	Kd	6.2	nM	FORETINIB
8.19	Kd	6.5	nM	CHEMBL386051
8.15	Kd	7	nM	REGORAFENIB
8.10	Kd	8	nM	TESEVATINIB
8.00	Kd	10	nM	SARACATINIB
8.00	Kd	10	nM	CHEMBL450519
8.00	IC50	10.1	nM	CHEMBL6172486
7.83	Kd	14.79	nM	DASATINIB ANHYDROUS
7.82	Kd	15	nM	DASATINIB
7.82	Kd	15	nM	SAPITINIB
7.82	Kd	15	nM	DASATINIB ANHYDROUS
7.59	Kd	25.73	nM	CHEMBL3752910
7.51	IC50	31	nM	MIVAVOTINIB
7.51	IC50	30.6	nM	DASATINIB ANHYDROUS
7.41	Kd	39	nM	TAE-684
7.30	IC50	49.8	nM	STAUROSPORINE
7.19	ED50	64	nM	CHEMBL3752910
7.17	Kd	67	nM	R-406
7.04	Kd	91	nM	CHEMBL3688339
7.02	IC50	95.3	nM	STAUROSPORINE
7.02	IC50	95.3	nM	CHEMBL1276179
7.00	Kd	99	nM	CHEMBL1241674
6.96	IC50	110.3	nM	CHEMBL5598020
6.93	IC50	117	nM	STAUROSPORINE
6.86	IC50	139	nM	STAUROSPORINE
6.85	Kd	140	nM	CRIZOTINIB
6.84	IC50	143	nM	PONATINIB
6.84	IC50	145	nM	CHEMBL5425418
6.82	IC50	150	nM	REBASTINIB
6.82	Kd	150	nM	KW-2449
6.71	Kd	193	nM	ALECTINIB
6.64	Kd	230	nM	VANDETANIB
6.54	IC50	292	nM	CHEMBL5188373
6.52	IC50	303.4	nM	CHEMBL5092606
6.52	IC50	303.4	nM	CHEMBL3752910
6.52	Kd	300	nM	STAUROSPORINE
6.42	Kd	380	nM	LESTAURTINIB
6.41	IC50	392.9	nM	CHEMBL5089164
6.23	Kd	586	nM	CHEMBL4465866
6.23	Kd	588	nM	CHEMBL4576489
6.23	Kd	590	nM	NILOTINIB
6.20	IC50	630	nM	DORAMAPIMOD
6.16	IC50	686	nM	CHEMBL1923983
6.15	Kd	705	nM	DABRAFENIB
6.14	Kd	730	nM	FEDRATINIB
6.00	IC50	1000	nM	TP-030-1

PubChem BioAssay actives

86 with measured affinity, of 989 total; 50 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
7-(5-hydroxy-2-methylphenyl)-6-(2-methoxyphenyl)-4-methylpurino[7,8-a]imidazole-1,3-dione	441385: Inhibition of EphA1 by [gamma33-P]ATP based assay	ic50	0.0029	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435793: Binding constant for EPHA1 kinase domain	kd	0.0041	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389078: Binding affinity to human EPHA1	kd	0.0050	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	1424987: 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	0.0050	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	625008: Binding constant for EPHA1 kinase domain	kd	0.0062	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625008: Binding constant for EPHA1 kinase domain	kd	0.0065	uM
regorafenib anhydrous	1424987: 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	0.0070	uM
7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine	1424987: 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
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424987: 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	0.0100	uM
3-(4-amino-7-piperidin-4-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	389078: Binding affinity to human EPHA1	kd	0.0100	uM
Dasatinib	2147751: Binding affinity to human EPHA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0148	uM
2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-N-methylacetamide	1424987: 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	0.0150	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147751: Binding affinity to human EPHA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0257	uM
6-[[(1R,2S)-2-aminocyclohexyl]amino]-7-fluoro-4-(1-methylpyrazol-4-yl)-1,2-dihydropyrrolo[3,4-c]pyridin-3-one	1330032: Inhibition of human recombinant GST-tagged EPHA1 cytoplasmic domain (568 to 976 residues) expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0310	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	625008: Binding constant for EPHA1 kinase domain	kd	0.0390	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	1308943: Inhibition of EPHA1 (unknown origin) incubated for 1 hr by spectrophotometric analysis	ic50	0.0498	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	625008: Binding constant for EPHA1 kinase domain	kd	0.0670	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1424987: 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	0.0910	uM
7-[2,6-difluoro-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-3-(1H-indazol-4-yl)-2-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	535996: Inhibition of EPHA1	ic50	0.0953	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625008: Binding constant for EPHA1 kinase domain	kd	0.0990	uM
2-amino-5-[2-[(3R)-3-aminopyrrolidin-1-yl]-6-fluoro-4-pyridinyl]-3-(3-hydroxy-2,6-dimethylphenyl)benzamide	2122455: Inhibition of EphA1 (unknown origin)	ic50	0.1103	uM
Crizotinib	625008: Binding constant for EPHA1 kinase domain	kd	0.1400	uM
Ponatinib	1716406: Binding affinity to human EPHA1 using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay	ic50	0.1430	uM
8-(4-aminobutyl)-6-(2,5-difluorophenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1974630: Inhibition of full length NanoLuc fused EPHA1 (unknown origin) transfected in HEK293T cells using NanoBRET NanoGlo substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.1450	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625008: Binding constant for EPHA1 kinase domain	kd	0.1500	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168232: Inhibition of human wild type EPHA1 using PolyEY as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.1500	uM
Alectinib	1424987: 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	0.1930	uM
Vandetanib	435793: Binding constant for EPHA1 kinase domain	kd	0.2300	uM
5-bromo-4-N-(5-dimethylphosphoryl-2,3-dihydro-1,4-benzodioxin-6-yl)-2-N-[2-methoxy-4-[4-[3-(methoxymethyl)azetidin-1-yl]piperidin-1-yl]-5-methylphenyl]pyrimidine-2,4-diamine	1862874: Inhibition of EphA1 (unknown origin)	ic50	0.2920	uM
4-[[4-[(4-aminocyclohexyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N,N-dimethylbenzamide	1823019: Inhibition of human recombinant EPHA1 incubated for 1 hrs by HTRF KinEASE TK assay	ic50	0.3034	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	507919: Binding affinity to EPHA1	kd	0.3800	uM
6-[[4-[(4-aminocyclohexyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-2-methylisoquinolin-1-one	1823019: Inhibition of human recombinant EPHA1 incubated for 1 hrs by HTRF KinEASE TK assay	ic50	0.3929	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	1526240: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged EPHA1 (unknown origin) (586 to 976 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.5860	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]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526240: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged EPHA1 (unknown origin) (586 to 976 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.5880	uM
Nilotinib	625008: Binding constant for EPHA1 kinase domain	kd	0.5900	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	636421: Inhibition of EPHA1	ic50	0.6300	uM
2-methoxy-N-[[6-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]-2-pyridinyl]methyl]acetamide	631826: Inhibition of EPHA1	ic50	0.6860	uM
Dabrafenib	1424987: 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	0.7050	uM
Fedratinib	625008: Binding constant for EPHA1 kinase domain	kd	0.7300	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435793: Binding constant for EPHA1 kinase domain	kd	1.0000	uM
Tovorafenib	1424987: 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	1.0670	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625008: Binding constant for EPHA1 kinase domain	kd	1.2000	uM
6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine	1673294: Binding affinity to human wild type partial length EphA1 (V588 to I913 residues) expressed in bacterial expression system by Kinomescan method	kd	1.3000	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	435793: Binding constant for EPHA1 kinase domain	kd	1.8000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147751: Binding affinity to human EPHA1 incubated for 45 mins by Kinobead based pull down assay	kd	1.8197	uM
(3S)-3-[[(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]-4-(1H-indol-3-yl)butanoic acid	2128418: Displacement of biotinylated Fc-tagged ephrin-A1 from N/C-terminal 6-his tagged human recombinant EphA1 (Lys26 to Glu547 residues) preincubated for 1 hr followed by ephrin-A1-Fc addition and measured after 4 to 5 hrs by ELISA assay	ic50	2.2000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	625008: Binding constant for EPHA1 kinase domain	kd	2.3000	uM
Bosutinib	625008: Binding constant for EPHA1 kinase domain	kd	2.3000	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	728720: Displacement of ephrin-A1-Fc from EphA1 receptor Fc ectodomain (unknown origin) after 1 hr by ELISA	ic50	2.3000	uM
N-[4-[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]cyclohexyl]acetamide	2117493: Inhibition of human EPHA1 incubated for 1 hr by HTRF assay	ic50	2.4830	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Aflatoxin B1	decreases expression, increases methylation	4
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Arsenic	affects methylation, decreases expression, increases abundance	2
GSK-J4	decreases expression	1
daidzein	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases expression, increases abundance	1
afimoxifene	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
antimonite	increases abundance, decreases expression	1
glycitein	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
GW 7604	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ON 01910	increases phosphorylation	1
dorsomorphin	increases expression, affects cotreatment	1
ponatinib	decreases activity	1
Bortezomib	decreases expression	1
Resveratrol	increases expression	1

ChEMBL screening assays

284 unique, capped per target: 284 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1006307	Binding	Inhibition of EPHA1 at 1 uM relative to control	Structure-based drug design of novel Aurora kinase A inhibitors: structural basis for potency and specificity. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1RB	Abcam HeLa EPHA1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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