EPHB1

Summary

EPHB1 (EPH receptor B1, HGNC:3392) is a protein-coding gene on chromosome 3q22.2, encoding Ephrin type-B receptor 1 (P54762). Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of 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. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members.

Source: NCBI Gene 2047 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 137 total
• Phenotypes (HPO): 1
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3392
Approved symbol	EPHB1
Name	EPH receptor B1
Location	3q22.2
Locus type	gene with protein product
Status	Approved
Aliases	Hek6
Ensembl gene	ENSG00000154928
Ensembl biotype	protein_coding
OMIM	600600
Entrez	2047

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000398015, ENST00000473867, ENST00000474732, ENST00000482618, ENST00000488154, ENST00000488992, ENST00000493838, ENST00000497173, ENST00000647596, ENST00000895120, ENST00000928305, ENST00000970111

RefSeq mRNA: 1 — MANE Select: NM_004441 NM_004441

CCDS: CCDS46921

Canonical transcript exons

ENST00000398015 — 16 exons

Exon	Start	End
ENSE00001329897	134951371	134952052
ENSE00001855733	135259012	135260467
ENSE00002206582	135166942	135167006
ENSE00002241250	135192576	135192823
ENSE00002254675	135162018	135162180
ENSE00002276292	135249336	135249491
ENSE00002308795	135165968	135166076
ENSE00002309733	135179860	135179982
ENSE00002324505	135248316	135248509
ENSE00002331267	135241148	135241297
ENSE00002399951	135201474	135201689
ENSE00003520300	135132714	135133049
ENSE00003544577	135106448	135106603
ENSE00003567785	134925816	134925880
ENSE00003581614	135154152	135154276
ENSE00003845684	134795260	134795689

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0219 / max 748.9191, expressed in 989 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38721	10.0676	902
38719	1.0812	44
38722	0.4519	205
38723	0.2728	134
202938	0.1380	26
38727	0.0105	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.12	gold quality
endothelial cell	CL:0000115	91.61	gold quality
ganglionic eminence	UBERON:0004023	90.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.67	gold quality
secondary oocyte	CL:0000655	88.14	gold quality
cerebellum	UBERON:0002037	85.70	gold quality
cerebellar cortex	UBERON:0002129	85.67	gold quality
ventricular zone	UBERON:0003053	85.62	gold quality
cerebellar hemisphere	UBERON:0002245	85.60	gold quality
primary visual cortex	UBERON:0002436	84.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.46	gold quality
cerebellar vermis	UBERON:0004720	84.03	gold quality
caudate nucleus	UBERON:0001873	83.59	gold quality
putamen	UBERON:0001874	83.37	gold quality
middle temporal gyrus	UBERON:0002771	81.11	gold quality
paraflocculus	UBERON:0005351	79.98	gold quality
oocyte	CL:0000023	79.88	gold quality
occipital lobe	UBERON:0002021	78.87	gold quality
blood	UBERON:0000178	78.83	gold quality
right frontal lobe	UBERON:0002810	78.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.36	gold quality
prefrontal cortex	UBERON:0000451	77.66	gold quality
neocortex	UBERON:0001950	77.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.21	gold quality
telencephalon	UBERON:0001893	77.17	gold quality
nucleus accumbens	UBERON:0001882	76.86	gold quality
frontal cortex	UBERON:0001870	76.70	gold quality
cerebral cortex	UBERON:0000956	76.64	gold quality
cingulate cortex	UBERON:0003027	76.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.60	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	13.47
E-ANND-3	yes	5.78
E-ENAD-17	no	265.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, ISL2, PAX6, SP1

miRNA regulators (miRDB)

157 targeting EPHB1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893

Literature-anchored findings (GeneRIF, showing 28)

• Human platelets express EphA4 and EphB1, and the ligand, ephrinB1. Forced clustering of EphA4 or ephrinB1 led to cytoskeletal reorganization, adhesion to fibrinogen, and alpha-granule secretion. (PMID:12084815)
• Eph/ephrin signaling enhances the ability of platelet agonists to cause aggregation provided that those agonists can increase cytosolic Ca(++) and this is accomplished in part by activating Rap1 (PMID:14576067)
• analysis of EphB1, EphB2, and EphB4-binding peptides interaction with antagonists with ephrin-like affinity (PMID:15722342)
• The ubiquitin ligase Cbl induces the ubiquitination and lysosomal degradation of activated EphB1, a process requiring EphB1 and Src kinase activity. (PMID:18034775)
• Transgenic EphB1 and ephrin-B3 cooperatively regulate the proliferation and migration of neural progenitors in the hippocampus. (PMID:18057206)
• Loss of expression of EphB1 protein in gastric carcinoma is associated with invasion and metastasis (PMID:18424888)
• EphB1 may have roles in the pathogenesis and development of colorectal cancer. (PMID:18931529)
• No association is found for EPH receptor B1 and susceptibility to schizophrenia. (PMID:21041834)
• Data shew that the identification of three novel candidates as EPH receptor genes might indicate a link between perturbed compartmentalization of early neoplastic lesions and breast cancer risk and progression. (PMID:21124932)
• EPHB1 polymorphisms may be associated with susceptibility to hepatocellular carcinoma in the Korean population. (PMID:21763378)
• Data show that EphB receptors interact with E-cadherin and with the metalloproteinase ADAM10 at sites of adhesion. (PMID:21804545)
• EphB1 stimulation triggered approximately 50% serine-threonine PTEN dephosphorylation and PTEN-Cbl complex disruption, a process requiring PTEN protein phosphatase activity. (PMID:23118026)
• Low EphB1 expression is associated with glioma. (PMID:24121831)
• Our data indicate that loss of EphB1 protein is associated with metastasis and poorer survival in patients with serous ovarian cancer (PMID:24427352)
• EphB1 and Ephrin-B could be regarded as independent good prognostic factors and important biological markers for Squamous cell/adenosquamous carcinoma and adenocarcinoma of gallbladder. (PMID:24606480)
• The study presents the first structure of the EphB1 tyrosine kinase domain determined by X-ray crystallography to 2.5A. (PMID:24677421)
• The genes CD248, Ephb1 and P2RY2 were detected as the top overexpressed in GC biopsies. (PMID:24716914)
• Our results indicate that EphB1 may be involved in carcinogenesis of renal cell carcinoma (PMID:25120806)
• In medulloblastoma cell lines, EphB1 downregulation or knockdown reduced cell growth, viability, cell-cycle regulator expression, and migration, but increased radiosensitivity and the percentage of cells in G1 phase of the cell cycle. (PMID:25879388)
• The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell transforming pathways. (PMID:25944917)
• Association of EPHB1 rs11918092 with symptoms of schizophrenia in Chinese Zhuang and Han populations. (PMID:27028544)
• investigate NET could modulate one’s attention orientation to facial expressions, we categorized individuals according to the genotypes of the -182 T/C (rs2242446) polymorphism. Our results indicated that the -182 T/C polymorphism significantly modulated attention orientation to facial expressions, of which the CC genotype facilitated attention reorientation to the locations where cued faces were previously presented. (PMID:27541794)
• some of the mutations found in EPHB1 may contribute to an increased invasive capacity of cancers. (PMID:28108514)
• SUMOylation of EphB1 repressed activation of its downstream signaling molecule PKC-gamma, and consequently inhibited neuroblastoma tumorigenesis. (PMID:29550816)
• 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)
• Peripheral EphrinB1/EphB1 signalling attenuates muscle hyperalgesia in MPS patients and a rat model of taut band-associated persistent muscle pain. (PMID:33356837)
• Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain. (PMID:33627480)
• Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells. (PMID:38102712)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ephb1	ENSDARG00000076757
danio_rerio		ENSDARG00000109215
mus_musculus	Ephb1	ENSMUSG00000032537
rattus_norvegicus	Ephb1	ENSRNOG00000007865

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), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Ephrin type-B receptor 1 — P54762 (reviewed: P54762)

Alternative names: ELK, EPH tyrosine kinase 2, EPH-like kinase 6, Neuronally-expressed EPH-related tyrosine kinase, Tyrosine-protein kinase receptor EPH-2

All UniProt accessions (6): P54762, A0A3B3IRY8, C9J466, C9J6S4, C9K090, F8WDG5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation.

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 with EPHB6; transphosphorylates EPHB6 to form an active signaling complex. Interacts with PICK1. Interacts (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade to regulate cell adhesion. The ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The ligand-activated form interacts (residues within the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell migration. Interacts with CBL; regulates receptor degradation through ubiquitination. Interacts with ACP1.

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

Tissue specificity. Preferentially expressed in brain.

Post-translational modifications. Phosphorylated. Autophosphorylation is stimulated by the ligand EFNB1. Required for interaction with SH2 domain-containing interactors, for activation of the MAPK/ERK and JUN signaling cascades and for ubiquitination by CBL. Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi-ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P54762-1	1	yes
P54762-5	2
P54762-6	3

RefSeq proteins (1): NP_004432* (*=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
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
IPR034231	EphB1_rcpt_lig-bd	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR042819	EphB1_SAM	Domain
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 (88 total): helix 19, strand 17, sequence variant 13, sequence conflict 9, mutagenesis site 5, domain 5, glycosylation site 3, splice variant 3, turn 3, binding site 2, modified residue 2, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7KPM	X-RAY DIFFRACTION	1.61
6UMW	X-RAY DIFFRACTION	1.98
5MJA	X-RAY DIFFRACTION	2.14
5MJB	X-RAY DIFFRACTION	2.23
3ZFX	X-RAY DIFFRACTION	2.5
7KPL	X-RAY DIFFRACTION	2.71
2DJS	SOLUTION NMR
2EAO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54762-F1	83.95	0.50

Functional residue map

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

Catalytic / active sites (1): 744 (proton acceptor)

Ligand- & substrate-binding residues (2): 625–633; 651

Post-translational modifications (2): 600, 928

Glycosylation sites (3): 334, 426, 480

Mutagenesis-validated functional residues (5):

Position	Phenotype
594	loss of interaction with nck1.
600	loss of interaction with shc1 and src.
651	kinase-dead mutant. unable to autophosphorylate, to interact with sh2 domain-containing interactors, to activate the map
778	loss of interaction with shc1.
928	disrupts binding with the grb10 sh2 domain, providing evidence for phosphorylation. disrupts interaction with grb7 and a

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-3928664	Ephrin signaling
R-HSA-3928665	EPH-ephrin mediated repulsion of cells

MSigDB gene sets: 358 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, E2F_Q4, GOBP_HINDBRAIN_DEVELOPMENT, E2F_Q4_01, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, E2F4DP1_01, GOBP_CELL_CHEMOTAXIS, MODULE_571

GO Biological Process (32): angiogenesis (GO:0001525), immunological synapse formation (GO:0001771), axon guidance (GO:0007411), skeletal muscle satellite cell activation (GO:0014719), optic nerve morphogenesis (GO:0021631), hindbrain tangential cell migration (GO:0021934), central nervous system projection neuron axonogenesis (GO:0021952), neurogenesis (GO:0022008), establishment of cell polarity (GO:0030010), retinal ganglion cell axon guidance (GO:0031290), cell-substrate adhesion (GO:0031589), regulation of JNK cascade (GO:0046328), protein autophosphorylation (GO:0046777), ephrin receptor signaling pathway (GO:0048013), camera-type eye morphogenesis (GO:0048593), modulation of chemical synaptic transmission (GO:0050804), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), positive regulation of synapse assembly (GO:0051965), cell chemotaxis (GO:0060326), dendritic spine development (GO:0060996), dendritic spine morphogenesis (GO:0060997), neural precursor cell proliferation (GO:0061351), regulation of ERK1 and ERK2 cascade (GO:0070372), negative regulation of skeletal muscle satellite cell proliferation (GO:1902723), negative regulation of satellite cell differentiation (GO:1902725), protein phosphorylation (GO:0006468), cell adhesion (GO:0007155), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), nervous system development (GO:0007399), cell migration (GO:0016477), cranial nerve development (GO:0021545), system development (GO:0048731)

GO Molecular Function (12): transmembrane-ephrin receptor activity (GO:0005005), ATP binding (GO:0005524), axon guidance receptor activity (GO:0008046), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ephrin receptor activity (GO:0005003), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (15): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), axon (GO:0030424), dendrite (GO:0030425), early endosome membrane (GO:0031901), filopodium tip (GO:0032433), membrane raft (GO:0045121), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
EPH-Ephrin signaling	3
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
axon guidance	2
binding	2
cytoplasm	2
endomembrane system	2
neuron projection	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell-cell recognition	1
lymphocyte activation	1
axonogenesis	1
neuron projection guidance	1
cell activation	1
optic nerve development	1
cranial nerve morphogenesis	1
cell migration in hindbrain	1
central nervous system neuron axonogenesis	1
nervous system development	1
cell differentiation	1
establishment or maintenance of cell polarity	1
cell adhesion	1
JNK cascade	1
regulation of MAPK cascade	1
protein phosphorylation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
camera-type eye development	1
eye morphogenesis	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
sensory perception of pain	1
detection of temperature stimulus involved in sensory perception	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
dendrite development	1
anatomical structure development	1

Protein interactions and networks

STRING

2050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHB1	EFNB1	P98172	998
EPHB1	EFNB2	P52799	997
EPHB1	EFNB3	Q15768	982
EPHB1	EFNA4	P52798	908
EPHB1	EFNA1	P20827	841
EPHB1	ZIC2	O95409	835
EPHB1	EFNA2	O43921	778
EPHB1	EPHB6	O15197	777
EPHB1	EFNA3	P52797	747
EPHB1	ISL2	Q96A47	733
EPHB1	SHC1	P29353	720
EPHB1	EFNA5	P52803	710
EPHB1	NCK1	P16333	625
EPHB1	NCK2	O43639	621
EPHB1	GRB7	Q14451	615

IntAct

51 interactions, top by confidence:

A	B	Type	Score
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
GRB7	EPHB1	psi-mi:“MI:0915”(physical association)	0.510
EPHB1	GRB7	psi-mi:“MI:0915”(physical association)	0.510
GRB10	EPHB1	psi-mi:“MI:0915”(physical association)	0.500
GRB2	EPHB1	psi-mi:“MI:0915”(physical association)	0.500
EPHB1	GRB2	psi-mi:“MI:0914”(association)	0.500
EFNB1	EPHB1	psi-mi:“MI:0407”(direct interaction)	0.440
EPHB1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
EPHB1	Grb10	psi-mi:“MI:0915”(physical association)	0.370
Grb2	EPHB1	psi-mi:“MI:0915”(physical association)	0.370
Nck1	EPHB1	psi-mi:“MI:0915”(physical association)	0.370
	SGK1	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
EPHB1	Ptpn6	psi-mi:“MI:0914”(association)	0.350
EPHB2	BANF1	psi-mi:“MI:0914”(association)	0.350
EPHB4	EPHA3	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MALL	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC40A1	UBR5	psi-mi:“MI:0914”(association)	0.350
SLC6A7	ABCB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): EPHB1 (Two-hybrid), EPHB1 (Affinity Capture-MS), EPHB1 (PCA), EPHB1 (Protein-RNA), GJB1 (Biochemical Activity), EPHB1 (Affinity Capture-Western), ACP1 (Affinity Capture-Western), ACP1 (Reconstituted Complex), EPHB1 (Affinity Capture-RNA), EPHB1 (Reconstituted Complex), EPHB1 (Affinity Capture-MS), GRB2 (Two-hybrid), GRB10 (Two-hybrid), EPHB1 (Affinity Capture-MS), EPHB1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNK3, A2RT60, A4IHA1, A6YFB5, A9JRB3, B3LVG7, B3P3J9, B4G316, B4HEM8, B4JTT7, B4K835, B4LY58, B4N937, B4PST0, B4QZU6, D3ZA76, D3ZKF5, E1BJW1, F1N152, O13146, O42422, O43464, O88917, O97831, P09759, P09958, P23188, P23377, P29317, P54753, P54754, P54759, P54762, P83105, P83110, Q03145, Q07497, Q1KL86, Q28193, Q297U2

Diamond homologs: A0JM20, A0M8R7, A0M8S8, A1X150, D2IYS2, H2KZU7, O02466, O35346, O73798, P00521, P00529, P06213, P08069, P08581, P08922, P08923, P08941, P09208, P09760, P11362, P14616, P14617, P15127, P15208, P16056, P16092, P16591, P20806, P22607, P23049, P24062, P30530, P33497, P34152, P34925, P54762, P55144, P55146, P57097, P70451

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
EFNB1	up-regulates	EPHB1	binding
EPHB1	“up-regulates activity”	NRCAM	phosphorylation
EPHB1	“up-regulates activity”	STAT3	phosphorylation
EPHB1	“down-regulates quantity by destabilization”	CAV1	phosphorylation
EPHB1	“up-regulates activity”	EPHB1	phosphorylation
EPHB1	“up-regulates activity”	CASKIN1	phosphorylation
CNKSR1	“up-regulates activity”	EPHB1	binding
EPHB1	“up-regulates activity”	MAP2K4	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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.

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	45.2×	6e-05
epidermal growth factor receptor signaling pathway	5	32.6×	2e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	6	8.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

5602 predictions. Top by Δscore:

Variant	Effect	Δscore
3:134840529:GCC:G	donor_gain	1.0000
3:134840531:C:G	donor_gain	1.0000
3:134925807:A:AG	acceptor_gain	1.0000
3:134925808:A:G	acceptor_gain	1.0000
3:134925811:TACA:T	acceptor_loss	1.0000
3:134925812:ACAG:A	acceptor_loss	1.0000
3:134925813:CAGA:C	acceptor_loss	1.0000
3:134925814:A:AG	acceptor_gain	1.0000
3:134925814:AGAA:A	acceptor_loss	1.0000
3:134925815:G:A	acceptor_loss	1.0000
3:134925815:G:GG	acceptor_gain	1.0000
3:134925815:GA:G	acceptor_gain	1.0000
3:134925815:GAA:G	acceptor_gain	1.0000
3:134925815:GAAAC:G	acceptor_gain	1.0000
3:134925878:GGG:G	donor_gain	1.0000
3:134925879:GGG:G	donor_gain	1.0000
3:134947485:G:GT	donor_gain	1.0000
3:134949865:G:GT	donor_gain	1.0000
3:134949918:T:G	donor_gain	1.0000
3:134951338:T:TA	acceptor_gain	1.0000
3:134951341:A:AG	acceptor_gain	1.0000
3:134951341:AT:A	acceptor_gain	1.0000
3:134951341:ATGT:A	acceptor_gain	1.0000
3:134951342:T:G	acceptor_gain	1.0000
3:134951344:T:TA	acceptor_gain	1.0000
3:134951346:T:TA	acceptor_gain	1.0000
3:134951348:T:TA	acceptor_gain	1.0000
3:134978106:G:GT	donor_gain	1.0000
3:135106443:TCTA:T	acceptor_loss	1.0000
3:135106444:CTAG:C	acceptor_loss	1.0000

AlphaMissense

6509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:134925857:T:A	W34R	1.000
3:134925857:T:C	W34R	1.000
3:134925859:G:C	W34C	1.000
3:134925859:G:T	W34C	1.000
3:134951371:T:A	W42R	1.000
3:134951371:T:C	W42R	1.000
3:134951372:G:C	W42S	1.000
3:134951373:G:C	W42C	1.000
3:134951373:G:T	W42C	1.000
3:134951413:C:A	R56S	1.000
3:134951428:T:A	C61S	1.000
3:134951428:T:C	C61R	1.000
3:134951429:G:A	C61Y	1.000
3:134951429:G:C	C61S	1.000
3:134951429:G:T	C61F	1.000
3:134951430:C:G	C61W	1.000
3:134951458:T:A	W71R	1.000
3:134951458:T:C	W71R	1.000
3:134951460:G:C	W71C	1.000
3:134951460:G:T	W71C	1.000
3:134951462:T:C	L72P	1.000
3:134951518:T:C	F91L	1.000
3:134951519:T:C	F91S	1.000
3:134951519:T:G	F91C	1.000
3:134951520:C:A	F91L	1.000
3:134951520:C:G	F91L	1.000
3:134951533:T:A	C96S	1.000
3:134951533:T:C	C96R	1.000
3:134951534:G:A	C96Y	1.000
3:134951534:G:C	C96S	1.000

dbSNP variants (sampled 300 via entrez): RS1000003446 (3:135200344 G>A), RS1000011060 (3:135067408 G>T), RS1000032978 (3:135220442 C>CTTCTAAT), RS1000039946 (3:134987540 A>C), RS1000041982 (3:135081474 A>G), RS1000042816 (3:135040285 G>A), RS1000072073 (3:134919125 A>G), RS1000074778 (3:134859198 G>T), RS1000083006 (3:135055434 A>T), RS1000089590 (3:134919364 G>C,T), RS1000091737 (3:135227481 A>G), RS1000093754 (3:134959683 C>G), RS1000096760 (3:135046855 A>C,G), RS1000096999 (3:135070643 G>A), RS1000104948 (3:135206438 G>C)

Disease associations

OMIM: gene MIM:600600 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000717	Autism

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001523_1	Visceral adipose tissue adjusted for BMI	3.000000e-06
GCST001524_39	Visceral adipose tissue/subcutaneous adipose tissue ratio	1.000000e-06
GCST002949_2	Epilepsy and lamotrigine-induced maculopapular eruptions	1.000000e-07
GCST003518_29	Daytime sleep phenotypes	3.000000e-06
GCST004571_2	Iron status biomarkers (total iron binding capacity)	5.000000e-07
GCST004571_5	Iron status biomarkers (total iron binding capacity)	2.000000e-07
GCST004572_11	Iron status biomarkers (transferrin saturation)	5.000000e-07
GCST004572_15	Iron status biomarkers (transferrin saturation)	2.000000e-07
GCST004746_26	Small cell lung carcinoma	2.000000e-06
GCST006087_34	Familial lung adenocarcinoma	2.000000e-07
GCST008155_62	Waist-hip ratio	6.000000e-07
GCST008159_10	Waist-to-hip ratio adjusted for BMI	9.000000e-06
GCST008357_24	Mood instability	2.000000e-08
GCST008521_25	Bitter beverage consumption	1.000000e-07
GCST008830_11	Neurofibrillary tangles	9.000000e-06
GCST009367_2	HDL cholesterol levels x short total sleep time interaction (2df test)	4.000000e-10
GCST010578_2	CV-A6-associated hand, foot, and mouth disease (severe vs mild)	4.000000e-06
GCST010988_115	Adult body size	1.000000e-09
GCST012226_634	Waist circumference adjusted for body mass index	1.000000e-10
GCST012226_635	Waist circumference adjusted for body mass index	5.000000e-12
GCST012226_636	Waist circumference adjusted for body mass index	5.000000e-09
GCST012231_190	A body shape index	3.000000e-11
GCST012231_191	A body shape index	2.000000e-13
GCST012490_58	Femur bone mineral density x serum urate levels interaction	3.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:1001253	maculopapular eruption
EFO:0007828	daytime rest measurement
EFO:0006334	total iron binding capacity
EFO:0006953	family history of lung cancer
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008475	mood instability measurement
EFO:0010089	bitter beverage consumption measurement
EFO:0006797	neurofibrillary tangles measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007863	illness severity status
EFO:0007789	BMI-adjusted waist circumference
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363043 (PROTEIN FAMILY), CHEMBL5072 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 560,126 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
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	3,096
CHEMBL1721885	SU-014813	2
CHEMBL475251	R-406	2
CHEMBL572878	TOZASERTIB	2
CHEMBL607707	PELITINIB	2
CHEMBL1908397	KW-2449	1
CHEMBL259084	MLN-8054	1
CHEMBL4439321	ATUVECICLIB	1
CHEMBL574738	AST-487	1

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	8.96	pIC50
compound 20 [PMID: 23489211]	Inhibition	5.42	pIC50

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 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
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 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
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

75 potent at pChembl≥5 of 76 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.35	Kd	0.45	nM	DASATINIB
8.96	IC50	1.1	nM	CHEMBL566515
8.36	Kd	4.4	nM	CHEMBL386051
8.22	IC50	6	nM	CHEMBL488840
7.92	Kd	12	nM	FORETINIB
7.70	IC50	20	nM	STAUROSPORINE
7.53	IC50	29.8	nM	CHEMBL4846921
7.48	Kd	33	nM	BOSUTINIB
7.39	IC50	40.6	nM	STAUROSPORINE
7.38	IC50	41.6	nM	CHEMBL5598020
7.22	IC50	60.3	nM	STAUROSPORINE
6.96	IC50	110	nM	DORAMAPIMOD
6.92	Kd	120	nM	CRIZOTINIB
6.89	IC50	127.9	nM	STAUROSPORINE
6.75	Kd	180	nM	AST-487
6.62	Kd	240	nM	STAUROSPORINE
6.54	Kd	290	nM	VANDETANIB
6.48	Kd	330	nM	MLN-8054
6.47	Kd	340	nM	TAE-684
6.41	IC50	388	nM	CHEMBL4793380
6.41	Kd	390	nM	R-406
6.32	Kd	480	nM	SUNITINIB
6.27	Kd	540	nM	VANDETANIB
6.26	Kd	550	nM	NINTEDANIB
6.23	Kd	590	nM	STAUROSPORINE
6.20	IC50	632	nM	CHEMBL5425418
6.06	Kd	880	nM	LINIFANIB
6.02	Kd	960	nM	SUNITINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	ERLOTINIB
5.96	IC50	1110	nM	CHEMBL1923983
5.89	Kd	1300	nM	GEFITINIB
5.89	Kd	1300	nM	NILOTINIB
5.85	Kd	1400	nM	CANERTINIB
5.82	Kd	1500	nM	CHEMBL1908395
5.82	Kd	1500	nM	ALVOCIDIB
5.82	Kd	1500	nM	CANERTINIB
5.80	Kd	1600	nM	NEFLAMAPIMOD
5.77	Kd	1700	nM	SORAFENIB
5.77	Kd	1700	nM	FEDRATINIB
5.72	Kd	1900	nM	TOZASERTIB
5.72	Kd	1900	nM	CHEMBL1241674
5.69	IC50	2032	nM	ATUVECICLIB
5.66	Kd	2200	nM	ALVOCIDIB
5.60	IC50	2500	nM	CHEMBL3734863
5.60	Kd	2500	nM	KW-2449
5.52	IC50	3039	nM	INFIGRATINIB
5.52	Kd	3000	nM	SORAFENIB

PubChem BioAssay actives

69 with measured affinity, of 777 total; 42 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	435403: Binding constant for EPHB1 kinase domain	kd	0.0004	uM
7-(5-hydroxy-2-methylphenyl)-6-(2-methoxyphenyl)-4-methylpurino[7,8-a]imidazole-1,3-dione	441392: Inhibition of EphB1 by [gamma33-P]ATP based assay	ic50	0.0011	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624954: Binding constant for EPHB1 kinase domain	kd	0.0044	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)purin-6-amine	363603: Inhibition of EphB1	ic50	0.0060	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	624954: Binding constant for EPHB1 kinase domain	kd	0.0120	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	1715363: Inhibition of human EPHB1 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0200	uM
N-[3-[2-[4-(4-ethylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-7-yl]phenyl]methanesulfonamide	1779450: Inhibition of EphB1 (unknown origin)	ic50	0.0298	uM
Bosutinib	624954: Binding constant for EPHB1 kinase domain	kd	0.0330	uM
2-amino-5-[2-[(3R)-3-aminopyrrolidin-1-yl]-6-fluoro-4-pyridinyl]-3-(3-hydroxy-2,6-dimethylphenyl)benzamide	2122457: Inhibition of EphB1 (unknown origin)	ic50	0.0416	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	636426: Inhibition of EPHB1	ic50	0.1100	uM
Crizotinib	624954: Binding constant for EPHB1 kinase domain	kd	0.1200	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435403: Binding constant for EPHB1 kinase domain	kd	0.1800	uM
Vandetanib	435403: Binding constant for EPHB1 kinase domain	kd	0.2900	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	435403: Binding constant for EPHB1 kinase domain	kd	0.3300	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	624954: Binding constant for EPHB1 kinase domain	kd	0.3400	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735604: Inhibition of recombinant human EphB1 (564 to end residues) using KVEKIGEGTYGVVYK as substrate incubated for 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay	ic50	0.3880	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	624954: Binding constant for EPHB1 kinase domain	kd	0.3900	uM
Sunitinib	435403: Binding constant for EPHB1 kinase domain	kd	0.4800	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624954: Binding constant for EPHB1 kinase domain	kd	0.5500	uM
8-(4-aminobutyl)-6-(2,5-difluorophenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1974626: Inhibition of full length NanoLuc fused EPHB1 (unknown origin) transfected in HEK293T cells using NanoBRET NanoGlo substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.6320	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	624954: Binding constant for EPHB1 kinase domain	kd	0.8800	uM
Momelotinib	2183893: Inhibition of EPHB1 (unknown origin)	ic50	1.0000	uM
Erlotinib	624954: Binding constant for EPHB1 kinase domain	kd	1.1000	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	631827: Inhibition of EphB1	ic50	1.1100	uM
Gefitinib	624954: Binding constant for EPHB1 kinase domain	kd	1.3000	uM
Nilotinib	624954: Binding constant for EPHB1 kinase domain	kd	1.3000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	256590: Average Binding Constant for EPHB1; NA=Not Active at 10 uM	kd	1.4000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624954: Binding constant for EPHB1 kinase domain	kd	1.5000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624954: Binding constant for EPHB1 kinase domain	kd	1.5000	uM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	256590: Average Binding Constant for EPHB1; NA=Not Active at 10 uM	kd	1.6000	uM
Fedratinib	624954: Binding constant for EPHB1 kinase domain	kd	1.7000	uM
Sorafenib	256590: Average Binding Constant for EPHB1; NA=Not Active at 10 uM	kd	1.7000	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624954: Binding constant for EPHB1 kinase domain	kd	1.9000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435403: Binding constant for EPHB1 kinase domain	kd	1.9000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624954: Binding constant for EPHB1 kinase domain	kd	2.5000	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	1260967: Displacement of biotinylated ephrin-B1-Fc from EphB1 (unknown origin) preincubated for 1 hr followed by biotinylated-ephrin-B1-Fc addition measured after 4 hrs by ELISA	ic50	2.5000	uM
3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea;phosphoric acid	623556: Inhibition of EPHB1-mediated proliferation of mouse BAF3 cells transformed with TEL-Kinase construct	ic50	3.0390	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	728713: Displacement of ephrin-B1-Fc from EphB1 receptor Fc ectodomain (unknown origin) after 1 hr by ELISA	ic50	3.8000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256590: Average Binding Constant for EPHB1; NA=Not Active at 10 uM	kd	4.2000	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	624954: Binding constant for EPHB1 kinase domain	kd	4.3000	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	507927: Binding affinity to EPHB1	kd	5.2000	uM
8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)-2-(4-piperidin-4-ylpiperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine	674646: Inhibition of EPHB1 by FRET assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases methylation	1
ochratoxin A	increases acetylation, increases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
diallyl trisulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
ponatinib	decreases activity	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Boron Compounds	increases expression	1
Drugs, Chinese Herbal	increases activity	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1

ChEMBL screening assays

273 unique, capped per target: 273 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024912	Binding	Binding affinity to human EPHB1 at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — 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_SM18	HAP1 EPHB1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms