gene

EPHB4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about EPHB4: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

174Connections

1Hypotheses

1Analyses

50Outgoing

50Incoming

3Experiments

2Debates

Summary

EPHB4 (Eph Receptor B4) is a member of the Eph receptor tyrosine kinase family that plays crucial roles in neural development, synaptic plasticity, cellular communication, and blood-brain barrier function. Dysregulated EPHB4 signaling has been implicated in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.

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🧬 Gene Info

Gene Symbol	Eph Receptor B4
Chromosome	5q22.1
Protein Type	Kinase
Target Class	Kinase
Function	Small molecule inhibitor of receptor tyrosine kinase activity
Mechanism of Action	Small molecule inhibitor of receptor tyrosine kinase activity
Primary Expression	the ventricular zone and cortical plate, coinciding with periods of active neurogenesis and neuronal migration
Druggability	Low (0.43)
Clinical Stage	Approved
Pathways	Ephrin-EphB receptor signaling
UniProt ID	Q541P7
NCBI Gene ID	2050
Ensembl ID	ENSG00000196411
OMIM	600010
Cerebral cortex	High expression in layer V pyramidal neurons, particularly in prefrontal and parietal cortices
Associated Diseases	AD, ALI, Als, cancer
Known Drugs/Compounds	Icariin
Interactions	ADAM17, AKT, AND, ANGPTL4, APOE, App
SciDEX Target	View Target Profile (7 clinical trials)
SciDEX Hypotheses	Ephrin-B2/EphB4 Axis Manipulation
KG Connections	174 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: EPHB4 — AlphaFold Q541P7 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

EPHB4 Gene

gene · 2157 words

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Pathway Diagram

flowchart TD
    h_e6437136["h-e6437136"] -->|"therapeutic target"| EPHB4["EPHB4"]
    h_e6437136["h-e6437136"] -->|"targets"| EPHB4["EPHB4"]
    AGGF1["AGGF1"] -->|"upregulates"| EPHB4["EPHB4"]
    EPHB4["EPHB4"] -->|"associated with"| Cancer["Cancer"]
    EPHB4["EPHB4"] -->|"interacts with"| Carcinoma["Carcinoma"]
    EPHB4["EPHB4"] -->|"interacts with"| Ms["Ms"]
    EPHB4["EPHB4"] -->|"interacts with"| Tumor["Tumor"]
    EPHB4["EPHB4"] -->|"associated with"| Ms["Ms"]
    EPHB4["EPHB4"] -->|"associated with"| Als["Als"]
    EPHB4["EPHB4"] -->|"activates"| Aging["Aging"]
    EPHB4["EPHB4"] -->|"activates"| Ms["Ms"]
    EPHB4["EPHB4"] -->|"activates"| Als["Als"]
    style h_e6437136 fill:#006494,stroke:#333,color:#e0e0e0
    style EPHB4 fill:#4a1a6b,stroke:#333,color:#e0e0e0
    style AGGF1 fill:#4a1a6b,stroke:#333,color:#e0e0e0
    style Cancer fill:#ef5350,stroke:#333,color:#e0e0e0
    style Carcinoma fill:#ef5350,stroke:#333,color:#e0e0e0
    style Ms fill:#ef5350,stroke:#333,color:#e0e0e0
    style Tumor fill:#ef5350,stroke:#333,color:#e0e0e0
    style Als fill:#ef5350,stroke:#333,color:#e0e0e0
    style Aging fill:#ef5350,stroke:#333,color:#e0e0e0

Outgoing (113)

Target	Relation	Type	Str
RASA1	interacts_with	entity	0.95
Epithelial-Mesenchymal Transition	associated_with	process	0.95
Esophageal Squamous Cell Carcinoma	involved_in	disease	0.90
VEIN OF GALEN MALFORMATION	associated_with	entity	0.90
Cerebrovascular Development	involved_in	process	0.90
Osteoporosis	regulates	disease	0.85
Glucocorticoid-Induced Osteoporosis	protects_against	disease	0.85
EFNB2	interacts_with	gene	0.85
Vein Of Galen Malformation	associated_with	disease	0.85
Esophageal Squamous Cell Carcinoma	drives	disease	0.80
RHOA	regulates	gene	0.80
Congenital Cerebrovascular Disease	associated_with	disease	0.80
Cell Proliferation	regulates	process	0.75
Ms	associated_with	disease	0.65
Ms	interacts_with	disease	0.65
Als	associated_with	disease	0.65
ALS	activates	disease	0.65
Cancer	causes	disease	0.65
Osteoporosis	activates	disease	0.65
ALS	causes	disease	0.65
Cardiac	associated_with	disease	0.65
Aging	activates	disease	0.65
Tumor	interacts_with	disease	0.65
Ms	activates	disease	0.65
Cancer	associated_with	disease	0.65
Carcinoma	interacts_with	disease	0.65
Als	activates	disease	0.65
Carcinoma	activates	disease	0.65
TNFA	interacts_with	gene	0.60
TNFA	associated_with	gene	0.60
ITGB8	interacts_with	gene	0.60
IL1B	associated_with	gene	0.60
RASA1	associated_with	gene	0.60
ERK	regulates	gene	0.60
USH2A	associated_with	gene	0.60
TGFB	associated_with	gene	0.60
IL1B	interacts_with	gene	0.60
IL6	interacts_with	gene	0.60
CANCER	associated_with	disease	0.60
Akt	interacts_with	pathway	0.60
TP53	associated_with	entity	0.60
ITGB8	associated_with	gene	0.60
APOE	associated_with	gene	0.60
TP53	causes	gene	0.60
RASA1	mediates	entity	0.60
RASA1	causes	entity	0.60
RHOA	expressed_in	entity	0.60
App	activates	protein	0.60
neurodegeneration	associated_with	disease	0.60
ALZHEIMER	activates	disease	0.60

Incoming (61)

Source	Relation	Type	Str
EPHRINB2	interacts_with	entity	0.95
EFNB2	interacts_with	gene	0.95
ICARIIN	upregulates	entity	0.90
h-e6437136	targets	hypothesis	0.90
Icariin	upregulates	compound	0.90
AGGF1	upregulates	gene	0.80
Glucocorticoid	downregulates	drug	0.80
Icariin	modulates	compound	0.80
RYR2	associated_with	gene	0.60
SCN1A	associated_with	gene	0.60
ROBO1	associated_with	gene	0.60
GAD2	associated_with	gene	0.60
PIK3CB	associated_with	gene	0.60
NOS1	associated_with	gene	0.60
CFTR	associated_with	gene	0.60
TP53	causes	gene	0.60
SRC	interacts_with	gene	0.60
EFNB1	associated_with	entity	0.60
ITGB8	associated_with	gene	0.60
ANGPTL4	associated_with	gene	0.60
ANGPTL4	interacts_with	gene	0.60
APOE	associated_with	gene	0.60
EFNB1	interacts_with	gene	0.60
TP53	interacts_with	gene	0.60
RASA1	associated_with	gene	0.60
AKT	interacts_with	gene	0.60
RHOA	activates	gene	0.60
IL1B	associated_with	gene	0.60
TNFA	associated_with	gene	0.60
USH2A	associated_with	gene	0.60
IL6	associated_with	gene	0.60
AKT	regulates	gene	0.60
EFNB1	regulates	gene	0.60
ERK	interacts_with	gene	0.60
CANCER	causes	gene	0.60
COMPLEMENT	activates	gene	0.60
CANCER	associated_with	entity	0.60
AND	interacts_with	gene	0.60
AND	associated_with	gene	0.60
AND	expressed_in	gene	0.60
GENES	associated_with	gene	0.60
TNFA	interacts_with	gene	0.50
IL1B	interacts_with	gene	0.50
ADAM17	interacts_with	protein	0.50
APOE	interacts_with	gene	0.50
C1QA	debate_co_mention	gene	0.45
CERS2	debate_co_mention	gene	0.45
CERS6	debate_co_mention	gene	0.45
AQP4	debate_co_mention	gene	0.45
C1Q	debate_co_mention	gene	0.45

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Ephrin-B2/EphB4 Axis Manipulation	0.645	neurodegeneration	4R-tau strain-specific spreading pattern

Mentioning Analyses (1)

Scientific analyses that reference this entity

4R-tau strain-specific spreading patterns in PSP vs CBD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.732

Experiments (3)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Spatial transcriptomic analysis of multistage ESCC development	exploratory	esophageal squamous-cell carci	0.850	human patients and mice	proposed	N/A
Functional analysis of EFNB1-EPHB4 interaction in EMT	exploratory	esophageal squamous-cell carci	0.800	cell culture systems and tissu	proposed	N/A
Analysis of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in cancer progression	exploratory	esophageal squamous-cell carci	0.750	human ESCC tissue samples and	proposed	N/A

Related Papers (17)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma [PMID:38097539]	Chen L, Zhu S, Liu T, Zhao X, Xiang T, H	Signal Transduct Target Ther	2023	1
Icariin Alleviates Glucocorticoid-Induced Osteoporosis through EphB4/Ephrin-B2 A [PMID:32508946]	Huang M, Wang Y, Peng R	Evid Based Complement Alternat	2020	1
EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease. [PMID:30819650]	Zeng X, Hunt A, Jin SC, Duran D, Gaillar	Trends Mol Med	2019	1
Working with children and young people in research: Supportive practices and pat [PMID:37186542]	["Thomas C", "Cockcroft E", "Jenkins G",	Journal of child health care :	2025	0
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC. [PMID:39489818]	Abdelazeem KNM, Nguyen D, Corbo S, Darra	Oncogene	2025	0
Replacing Dietary Fish Meal with Defatted Black Soldier Fly ( [PMID:35492617]	["Li X", "Qin C", "Fang Z", "Sun X", "Sh	Frontiers in physiology	2022	0
Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine [PMID:34756178]	["Declercq J", "Van Damme K", "De Leeuw	The Lancet. Respiratory medici	2021	0
Predictive factors of volumetric reduction in lumbar disc herniation treated by [PMID:32945283]	["Negro A", "Paolucci A", "Russo C", "Di	Acta bio-medica : Atenei Parme	2020	0
Variation in Intensive Care Unit Intubation Practices in Pulmonary Critical Care [PMID:33728421]	["Brady A", "Brown W", "Denson J", "Wint	ATS scholar	2020	0
The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis [PMID:31420548]	["Rice K", "Batul K", "Whiteside J", "Ke	Nature communications	2019	0
A review of the impact of financing mechanisms on maternal health care in Austra [PMID:31752792]	["Fox H", "Topp S", "Callander E", "Lind	BMC public health	2019	0
Molecular identity of arteries, veins, and lymphatics. [PMID:30154011]	Wolf K, Hu H, Isaji T, Dardik A	Journal of vascular surgery	2019	0
Vitamin D3 Induces Gene Expression of Ox-LDL Scavenger Receptors in Streptozotoc [PMID:29766000]	Alizadeh S, Mirshafiey A, Djalali M, Alv	Reports of biochemistry & mole	2018	0
Focal molography is a new method for the in situ analysis of molecular interacti [PMID:28945239]	["Gatterdam V", "Frutiger A", "Stengele	Nature nanotechnology	2017	0
Translating RNA sequencing into clinical diagnostics: opportunities and challeng [PMID:26996076]	["Byron S", "Van Keuren-Jensen K", "Enge	Nature reviews. Genetics	2016	0
Superimposed electrical stimulation improves mobility of pre-stiff thumbs after [PMID:24894392]	["Moineau B", "Boisgontier M"]	Annals of physical and rehabil	2014	0
Metastatic soft tissue sarcoma diagnosed by small bowel video capsule endoscopy. [PMID:20368563]	Jennifer M Weiss; Steven Attia; Howard H	Journal of clinical oncology :	2010	0

Debates (2)

Multi-agent debates referencing this entity

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

closed · Rounds: 4 · Score: 0.69 · 2026-04-12

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

closed · Rounds: 7 · Score: 0.91 · 2026-04-10

Related Research

Hypotheses and analyses mentioning EPHB4 in their description or question text

No additional research found