Back to discover

Protein / target

Ephrin type-A receptor 8

Encoded byEPHA8P29322Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
Small-molecule tractable
Druggability
Approved Drug
1
Research papers

Protein at a glance

Biological role

Transmembrane-ephrin receptor

Strongest disease association

Neuroendocrine Tumors

Via encoding gene EPHA8 · Genetic evidence · score 0.50

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

1 papers · latest 1996

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

View complete UniProt function annotation

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

Subcellular location

Cell membraneCell projectionEarly endosome membrane
Domains and Gene Ontology detail (24)

Domains & features

Eph LBDFibronectin type-III 1Fibronectin type-III 2Protein kinaseSAM

Gene Ontology

  • Cdendrite
  • Cearly endosome membrane
  • Cneuron projection
  • Cplasma membrane
  • FATP binding
  • Fephrin receptor activity
  • FGPI-linked ephrin receptor activity
  • Fgrowth factor binding
  • Ftransmembrane-ephrin receptor activity
  • Paxon guidance
  • Pcell adhesion
  • Pephrin receptor signaling pathway

1005 aa · 111 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Receptor tyrosine kinase signallingUniProtCell migrationGOCell adhesionUniProt · GOImmune signallingUniProt · GO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands…

Cell migration

  • ·substrate-dependent cell migration

Cell adhesion

  • ·Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands…
  • ·cell adhesion
  • ·regulation of cell adhesion
  • ·regulation of cell adhesion mediated by integrin

Immune signalling

  • ·Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands…
  • ·substrate-dependent cell migration

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene EPHA8

Gene-level evidence surfaced through the gene EPHA8 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neuroendocrine Tumors
0.50Limited support

Genetic evidence dominant · Open Targets 0.30

Carcinoma, Non-Small-Cell Lung
0.49Limited support

Clinical evidence dominant · Open Targets 0.39

Neoplasms
0.49Limited support

Clinical evidence dominant · Open Targets 0.38

Cardiomyopathies
0.47Limited support

Genetic evidence dominant · Open Targets 0.29

View evidence synthesis (4)
Neuroendocrine TumorsLimited support
0.50
agreement 0.380.62
Genetic100%

Open Targets aggregate 0.30 · 1 independent evidence family

Carcinoma, Non-Small-Cell LungLimited support
0.49
agreement 0.350.62
Clinical93%RNA expression4%Literature3%

Open Targets aggregate 0.39 · 3 independent evidence families

NeoplasmsLimited support
0.49
agreement 0.330.64
Clinical88%Literature12%

Open Targets aggregate 0.38 · 2 independent evidence families

CardiomyopathiesLimited support
0.47
agreement 0.350.59
Genetic100%

Open Targets aggregate 0.29 · 1 independent evidence family

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Carcinoma, Non-Small-Cell Lung0.39
Neoplasms0.38
Neuroendocrine Tumors0.30
Cardiomyopathies0.29

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)
VANDETANIBApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and High-Quality Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 1996

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Xia Z · The Journal of neuroscience : the official journal of the Society for Neuroscience · 1996

Recent

Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism.

Xia Z · The Journal of neuroscience : the official journal of the Society for Neuroscience · 1996

Europe PMC papers linked directly to this protein.