{"gene":"EPHA8","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":1991,"finding":"EphA8 (Eek) encodes a receptor protein-tyrosine kinase of the Eph subclass, containing all conserved catalytic domain residues, most abundantly expressed in brain.","method":"cDNA cloning, Northern blot, sequence analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — original identification with molecular characterization, single lab","pmids":["1648701"],"is_preprint":false},{"year":1997,"finding":"EphA8 loss-of-function in mice causes aberrant axonal projections: tectal neurons in the superior colliculus fail to reach contralateral inferior colliculus targets and form an abnormal ipsilateral tract to cervical spinal cord, establishing EphA8 as required for axonal pathfinding.","method":"EphA8 knockout mice, axonal tracing, retrograde labeling","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — genetic knockout with defined neuroanatomical phenotype, replicated by multiple tracing methods","pmids":["9214628"],"is_preprint":false},{"year":1997,"finding":"EphA8 (Eek) receptor can be activated by at least three GPI-linked ephrin ligands: Elf-1/Cek7-L, Ehk1-L/Efl-2/Lerk3, and AL-1/RAGS, as demonstrated by binding and receptor phosphorylation assays.","method":"Fc-fusion chimeric ligand binding assays, receptor phosphorylation in NIH3T3 cells","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding and phosphorylation assays, single lab","pmids":["9053851"],"is_preprint":false},{"year":1999,"finding":"EphA8 has two major autophosphorylation sites, Tyr-615 (juxtamembrane) and Tyr-838 (kinase domain); Tyr-838 phosphorylation is required for catalytic activity, while phospho-Tyr-615 mediates preferential binding to the Fyn SH2 domain over Src and RasGAP SH2 domains. EphA8 and Fyn physically associate in intact cells, and Fyn is a downstream target mediating EphA8 effects on cell adhesion.","method":"2D phosphopeptide mapping, in vitro kinase assays, site-directed mutagenesis, in vitro SH2 binding, co-immunoprecipitation, dominant-negative Fyn overexpression","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 1 — in vitro kinase assay with mutagenesis, in vitro binding, and in-cell co-IP with functional validation","pmids":["10498895"],"is_preprint":false},{"year":1999,"finding":"EphA8 binds ephrin-A1 and ephrin-A4 (in addition to previously known ephrin-A2, -A3, -A5) but not transmembrane ephrin-B ligands, confirming EphA8 as a GPI-linked ephrin-dependent receptor tyrosine kinase.","method":"Fc-fusion chimeric ligand binding assays, receptor tyrosine phosphorylation in NIH3T3 fibroblasts","journal":"Molecules and cells","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding and phosphorylation assays, single lab","pmids":["10515610"],"is_preprint":false},{"year":2001,"finding":"EphA8 enhances cell adhesion to fibronectin via α5β1 and β3 integrins through a tyrosine kinase-independent mechanism that requires ephrin-A binding to the extracellular domain and the juxtamembrane segment of the intracellular domain. The p110γ isoform of PI3-kinase associates with EphA8 via the juxtamembrane segment and mediates integrin activation.","method":"Cell adhesion assays, kinase-inactive mutants, domain deletion mutants, wortmannin inhibition, in vitro binding, co-immunoprecipitation, dominant-negative p110γ overexpression","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 — multiple mutants, in vitro binding, pharmacological inhibition, and dominant-negative approach in two cell lines","pmids":["11416136"],"is_preprint":false},{"year":2003,"finding":"EphA8 phosphorylates and activates low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) in vitro, and activated LMW-PTP in turn dephosphorylates EphA8, suggesting a feedback-control mechanism for EphA8 autokinase activity.","method":"In vitro kinase assay, phosphatase activity assay","journal":"Journal of biochemistry and molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution, single lab, no in-cell validation","pmids":["12787484"],"is_preprint":false},{"year":2003,"finding":"Ligand-stimulated EphA8 signaling requires p110γ PI3-kinase activity to promote cell migration on fibronectin; a lipid kinase-inactive p110γ dominantly suppresses ephrin-A5-stimulated PI3-kinase activity and migration, in a manner independent of EphA8 tyrosine kinase activity.","method":"Ephrin-A5-Fc stimulation, lipid kinase-inactive dominant-negative p110γ, cell migration assay on fibronectin","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 2 — dominant-negative approach with functional migration readout, corroborates prior co-IP data from same group","pmids":["12681484"],"is_preprint":false},{"year":2005,"finding":"EphA8 induces neurite outgrowth in NG108-15 neuronal cells in a ligand-independent manner, requiring the tyrosine kinase domain but not tyrosine kinase activity, through sustained MAPK activation that drives MAPK relocalization from cytoplasm to nucleus.","method":"Deletion mutants, kinase-inactive mutants, pharmacological inhibitors, MAPK activity assay, subcellular fractionation/immunofluorescence in NG108-15 cells","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — multiple mutants and inhibitors with defined cellular phenotype, single lab","pmids":["15782114"],"is_preprint":false},{"year":2007,"finding":"Upon ephrin-A5 stimulation, PTB domain-containing Anks family proteins AIDA-1b and Odin associate with the juxtamembrane domain of EphA8 in a tyrosine kinase-independent manner. Odin acts as a physiologically relevant scaffold for EphA8 signaling; its knockdown diminishes ephrin-A5-induced inhibition of cell migration and neurite retraction.","method":"Co-immunoprecipitation, PTB domain pulldown, siRNA knockdown, cell migration assay, dominant-negative PTB domain overexpression","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP, domain mapping, siRNA knockdown with defined functional phenotype","pmids":["17875921"],"is_preprint":false},{"year":2010,"finding":"EphA8 undergoes clathrin-mediated endocytosis upon ephrin-A5 stimulation; the juxtamembrane region of EphA8 is required for endocytosis and for association with Tiam-1 (a Rac-specific GEF). Tiam-1 knockdown impairs endocytosis of EphA8-ephrin-A5 complexes and reduces Rac activation.","method":"EphA8 deletion mutants, clathrin-mediated endocytosis assay, co-immunoprecipitation with Tiam-1, Rac activity assay, Tiam-1 siRNA knockdown","journal":"Molecules and cells","confidence":"Medium","confidence_rationale":"Tier 2 — domain mapping, co-IP, siRNA knockdown with functional readouts, single lab","pmids":["20496116"],"is_preprint":false},{"year":2012,"finding":"RINL (a Rab5 subfamily GEF) interacts with Odin and forms a ternary complex with EphA8. RINL expression reduces EphA8 protein levels in a manner dependent on both RINL GEF activity and Odin interaction, placing RINL in the EphA8 degradation pathway via Rab5-mediated trafficking.","method":"Co-immunoprecipitation, GEF activity assay (GTP-bound Rab measurement), RINL knockdown, overexpression in HeLa cells","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — co-IP, GEF assay, and knockdown with EphA8 level readout, single lab","pmids":["22291991"],"is_preprint":false},{"year":2013,"finding":"EphA8-Fc ectopic expression in transgenic embryos induces caspase-dependent apoptosis of ephrin-A5-expressing neural epithelial cells via reverse signaling through ephrin-As, causing reduced brain size.","method":"Transgenic embryo expression of EphA8-Fc, in vitro neuroepithelial cell culture with EphA8-Fc, caspase inhibitor assays, apoptosis quantification","journal":"Developmental neurobiology","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo transgenic and in vitro culture with caspase inhibitor functional validation, single lab","pmids":["23696555"],"is_preprint":false}],"current_model":"EphA8 is a GPI-linked ephrin-A-activated receptor tyrosine kinase that signals through both kinase-dependent (autophosphorylation at Tyr-838 enabling Tyr-615 phosphorylation and Fyn recruitment; sustained MAPK activation for neurite outgrowth) and kinase-independent mechanisms (juxtamembrane segment recruits p110γ PI3-kinase to promote integrin-mediated cell adhesion and migration, and scaffolds Odin/Anks proteins for migration inhibition), undergoes Tiam-1-regulated clathrin-mediated endocytosis with Rab5/RINL-dependent degradation, and is required in vivo for axonal pathfinding in the developing superior colliculus."},"narrative":{"teleology":[{"year":1991,"claim":"Identification of EphA8 (Eek) as a brain-enriched Eph-family receptor tyrosine kinase established the gene's molecular identity and tissue expression context.","evidence":"cDNA cloning, Northern blot, and sequence analysis from mouse cDNA","pmids":["1648701"],"confidence":"Medium","gaps":["No functional data on kinase activity or ligand specificity","Expression data limited to Northern blot without cellular resolution"]},{"year":1997,"claim":"Knockout mice revealed that EphA8 is required for axonal pathfinding in the superior colliculus, with tectal neurons forming aberrant ipsilateral tracts to cervical spinal cord instead of reaching contralateral targets, establishing the first in vivo function.","evidence":"EphA8 knockout mice with axonal tracing and retrograde labeling","pmids":["9214628"],"confidence":"High","gaps":["Downstream signaling pathways mediating the pathfinding phenotype unknown","Whether phenotype is cell-autonomous was not addressed"]},{"year":1997,"claim":"Ligand specificity was defined: EphA8 binds multiple GPI-linked ephrin-A ligands (ephrin-A1–A5) but not transmembrane ephrin-B ligands, classifying it as an EphA receptor.","evidence":"Fc-fusion ligand binding assays and receptor phosphorylation in NIH3T3 cells across two studies","pmids":["9053851","10515610"],"confidence":"Medium","gaps":["Relative binding affinities for individual ephrin-A ligands not quantified","In vivo relevance of specific ephrin-A partners not resolved"]},{"year":1999,"claim":"Mapping of autophosphorylation sites (Tyr-838 for catalytic activation, Tyr-615 for Fyn SH2 recruitment) and demonstration of EphA8–Fyn physical association established the kinase-dependent signaling axis controlling cell adhesion.","evidence":"2D phosphopeptide mapping, site-directed mutagenesis, in vitro SH2 binding, co-immunoprecipitation, dominant-negative Fyn","pmids":["10498895"],"confidence":"High","gaps":["Fyn substrates downstream of EphA8 not identified","Structural basis of SH2 selectivity for Fyn over Src/RasGAP unknown"]},{"year":2001,"claim":"A kinase-independent signaling arm was uncovered: the juxtamembrane segment recruits p110γ PI3-kinase to activate α5β1/β3 integrins for fibronectin adhesion and migration, independent of EphA8 catalytic activity.","evidence":"Kinase-inactive and domain-deletion mutants, wortmannin inhibition, co-immunoprecipitation, dominant-negative p110γ in two cell lines","pmids":["11416136","12681484"],"confidence":"High","gaps":["Direct binding interface between juxtamembrane segment and p110γ not mapped","How p110γ lipid kinase products activate integrins remains unclear"]},{"year":2005,"claim":"EphA8 drives neurite outgrowth via sustained MAPK activation and nuclear MAPK translocation, requiring the kinase domain but not kinase activity, revealing a scaffolding function of the kinase domain.","evidence":"Deletion and kinase-inactive mutants, pharmacological MAPK inhibitors, subcellular fractionation in NG108-15 neuronal cells","pmids":["15782114"],"confidence":"Medium","gaps":["How the inactive kinase domain scaffolds MAPK activation is mechanistically undefined","Ligand-independent context limits physiological extrapolation"]},{"year":2007,"claim":"Odin and AIDA-1b were identified as PTB-domain scaffolds recruited to the EphA8 juxtamembrane region in a kinase-independent manner; Odin knockdown diminished ephrin-A5-induced inhibition of migration and neurite retraction, establishing Odin as a physiological effector.","evidence":"Reciprocal co-immunoprecipitation, PTB domain pulldown, siRNA knockdown with migration and neurite retraction assays","pmids":["17875921"],"confidence":"High","gaps":["Odin downstream targets not identified","How Odin and p110γ share the juxtamembrane binding site is unresolved"]},{"year":2010,"claim":"EphA8 was shown to undergo clathrin-mediated endocytosis upon ephrin-A5 stimulation, regulated by Tiam-1 (a Rac GEF) binding to the juxtamembrane region, linking receptor trafficking to Rac activation.","evidence":"EphA8 deletion mutants, clathrin endocytosis assay, Tiam-1 co-immunoprecipitation and siRNA knockdown, Rac activity assay","pmids":["20496116"],"confidence":"Medium","gaps":["Direct Tiam-1 binding site on juxtamembrane region not mapped","Functional consequence of impaired endocytosis on downstream signaling not tested in neurons"]},{"year":2012,"claim":"RINL, a Rab5-family GEF, was placed in the EphA8 degradation pathway: RINL forms a ternary complex with Odin and EphA8, and RINL GEF activity reduces EphA8 protein levels via Rab5-dependent trafficking.","evidence":"Co-immunoprecipitation, GEF activity assay, RINL knockdown and overexpression in HeLa cells","pmids":["22291991"],"confidence":"Medium","gaps":["Lysosomal versus proteasomal route of EphA8 degradation not distinguished","In vivo relevance of RINL-mediated EphA8 turnover not tested"]},{"year":2013,"claim":"EphA8 ectodomain (EphA8-Fc) was shown to trigger caspase-dependent apoptosis in ephrin-A5-expressing neuroepithelial cells via reverse signaling, causing reduced brain size in transgenic embryos.","evidence":"Transgenic embryo EphA8-Fc expression, in vitro neuroepithelial culture with caspase inhibitors, apoptosis quantification","pmids":["23696555"],"confidence":"Medium","gaps":["Intracellular pathway from ephrin-A5 reverse signal to caspase activation not defined","Contribution of reverse versus forward signaling to the brain size phenotype not fully separated"]},{"year":null,"claim":"No structural model of EphA8 signaling complexes exists, the mechanism by which the kinase domain scaffolds MAPK independently of catalytic activity is unresolved, and the in vivo signaling pathways responsible for the superior colliculus axon guidance phenotype remain uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal structure of EphA8 intracellular domain or its complexes","Cell-type-specific conditional knockouts needed to resolve cell-autonomous functions","Integration of kinase-dependent and kinase-independent pathways in vivo not addressed"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,3,6]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[5,9]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2,5,10]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[10,11]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,5,7,8,9]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,12]}],"complexes":[],"partners":["FYN","PIK3CG","ANKS1A","ANKS1B","TIAM1","RINL","EFNA5"],"other_free_text":[]},"mechanistic_narrative":"EphA8 is a receptor tyrosine kinase of the Eph family that transduces GPI-linked ephrin-A signals to regulate axonal pathfinding, cell adhesion, migration, and neurite dynamics during neural development. EphA8 autophosphorylates at Tyr-838 (required for catalytic activity) and Tyr-615 (which recruits Fyn via its SH2 domain), and signals through both kinase-dependent sustained MAPK activation for neurite outgrowth and kinase-independent recruitment of p110γ PI3-kinase and Odin/AIDA-1b scaffolds via its juxtamembrane segment to control integrin-mediated adhesion and migration [PMID:10498895, PMID:11416136, PMID:15782114, PMID:17875921]. Ligand-stimulated EphA8 undergoes Tiam-1-regulated clathrin-mediated endocytosis and Rab5/RINL-dependent degradation [PMID:20496116, PMID:22291991]. Loss of EphA8 in mice causes aberrant axonal projections from the superior colliculus, establishing its requirement for axonal pathfinding in vivo [PMID:9214628]."},"prefetch_data":{"uniprot":{"accession":"P29322","full_name":"Ephrin type-A receptor 8","aliases":["EPH- and ELK-related kinase","EPH-like kinase 3","EK3","hEK3","Tyrosine-protein kinase receptor EEK"],"length_aa":1005,"mass_kda":111.0,"function":"Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. 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 membrane; Cell projection; Early endosome membrane","url":"https://www.uniprot.org/uniprotkb/P29322/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EPHA8","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/EPHA8","total_profiled":1310},"omim":[{"mim_id":"620678","title":"RAS AND RAB INTERACTOR-LIKE PROTEIN; RINL","url":"https://www.omim.org/entry/620678"},{"mim_id":"618462","title":"BLEEDING DISORDER, PLATELET-TYPE, 22; BDPLT22","url":"https://www.omim.org/entry/618462"},{"mim_id":"603688","title":"PROSTATE CANCER/BRAIN CANCER SUSCEPTIBILITY","url":"https://www.omim.org/entry/603688"},{"mim_id":"600997","title":"EPHRIN RECEPTOR EphB2; EPHB2","url":"https://www.omim.org/entry/600997"},{"mim_id":"176945","title":"EPHRIN RECEPTOR EphA8; EPHA8","url":"https://www.omim.org/entry/176945"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"choroid plexus","ntpm":31.5}],"url":"https://www.proteinatlas.org/search/EPHA8"},"hgnc":{"alias_symbol":["Hek3"],"prev_symbol":["EEK"]},"alphafold":{"accession":"P29322","domains":[{"cath_id":"2.60.120.260","chopping":"29-205","consensus_level":"high","plddt":89.081,"start":29,"end":205},{"cath_id":"2.60.40.1770","chopping":"208-263","consensus_level":"medium","plddt":90.2759,"start":208,"end":263},{"cath_id":"2.60.40.10","chopping":"333-436","consensus_level":"medium","plddt":91.1088,"start":333,"end":436},{"cath_id":"2.60.40.10","chopping":"447-532","consensus_level":"high","plddt":90.2473,"start":447,"end":532},{"cath_id":"3.30.200.20","chopping":"625-715","consensus_level":"high","plddt":81.8366,"start":625,"end":715},{"cath_id":"1.10.510.10","chopping":"720-903","consensus_level":"high","plddt":84.6943,"start":720,"end":903},{"cath_id":"1.10.150.50","chopping":"936-999","consensus_level":"high","plddt":80.3441,"start":936,"end":999}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P29322","model_url":"https://alphafold.ebi.ac.uk/files/AF-P29322-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P29322-F1-predicted_aligned_error_v6.png","plddt_mean":80.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EPHA8","jax_strain_url":"https://www.jax.org/strain/search?query=EPHA8"},"sequence":{"accession":"P29322","fasta_url":"https://rest.uniprot.org/uniprotkb/P29322.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P29322/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P29322"}},"corpus_meta":[{"pmid":"9214628","id":"PMC_9214628","title":"Aberrant axonal projections in mice lacking EphA8 (Eek) tyrosine protein kinase receptors.","date":"1997","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/9214628","citation_count":88,"is_preprint":false},{"pmid":"11416136","id":"PMC_11416136","title":"The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner.","date":"2001","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/11416136","citation_count":85,"is_preprint":false},{"pmid":"1648701","id":"PMC_1648701","title":"eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases.","date":"1991","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/1648701","citation_count":60,"is_preprint":false},{"pmid":"25683004","id":"PMC_25683004","title":"miR-10a controls glioma migration and invasion through regulating epithelial-mesenchymal transition via EphA8.","date":"2015","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/25683004","citation_count":55,"is_preprint":false},{"pmid":"15782114","id":"PMC_15782114","title":"The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells.","date":"2005","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/15782114","citation_count":40,"is_preprint":false},{"pmid":"10498895","id":"PMC_10498895","title":"Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity.","date":"1999","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/10498895","citation_count":28,"is_preprint":false},{"pmid":"17875921","id":"PMC_17875921","title":"Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function.","date":"2007","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17875921","citation_count":24,"is_preprint":false},{"pmid":"20496116","id":"PMC_20496116","title":"EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is regulated by Tiam-1, a Rac-specific guanine nucleotide exchange factor.","date":"2010","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/20496116","citation_count":22,"is_preprint":false},{"pmid":"9053851","id":"PMC_9053851","title":"The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands.","date":"1997","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/9053851","citation_count":20,"is_preprint":false},{"pmid":"23696555","id":"PMC_23696555","title":"Expression of EphA8-Fc in transgenic mouse embryos induces apoptosis of neural epithelial cells during brain development.","date":"2013","source":"Developmental neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/23696555","citation_count":19,"is_preprint":false},{"pmid":"33530159","id":"PMC_33530159","title":"Bone marrow stromal cells derived exosomal miR-10a and miR-16 may be involved in progression of patients with multiple myeloma by regulating EPHA8 or IGF1R/CCND1.","date":"2021","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33530159","citation_count":12,"is_preprint":false},{"pmid":"22291991","id":"PMC_22291991","title":"RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22291991","citation_count":12,"is_preprint":false},{"pmid":"12681484","id":"PMC_12681484","title":"The p110 gamma PI-3 kinase is required for EphA8-stimulated cell migration.","date":"2003","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/12681484","citation_count":11,"is_preprint":false},{"pmid":"17927897","id":"PMC_17927897","title":"Engineering lacZ Reporter gene into an ephA8 bacterial artificial chromosome using a highly efficient bacterial recombination system.","date":"2007","source":"Journal of biochemistry and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17927897","citation_count":10,"is_preprint":false},{"pmid":"10855796","id":"PMC_10855796","title":"Genomic structure and promoter analysis of the mouse EphA8 receptor tyrosine kinase gene.","date":"2000","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10855796","citation_count":9,"is_preprint":false},{"pmid":"12787484","id":"PMC_12787484","title":"The EphA8 receptor phosphorylates and activates low molecular weight phosphotyrosine protein phosphatase in vitro.","date":"2003","source":"Journal of biochemistry and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12787484","citation_count":9,"is_preprint":false},{"pmid":"12666197","id":"PMC_12666197","title":"Identification of an enhancer region in the mouse ephA8 locus directing expression to the anterior region of the dorsal mesencephalon.","date":"2003","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/12666197","citation_count":7,"is_preprint":false},{"pmid":"10515610","id":"PMC_10515610","title":"Characterization of ephrin-A1 and ephrin-A4 as ligands for the EphA8 receptor protein tyrosine kinase.","date":"1999","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/10515610","citation_count":7,"is_preprint":false},{"pmid":"22110341","id":"PMC_22110341","title":"Ectopic Expression of Ephrin-A5 Under the EphA8 Promoter at the Anterior Region of the Superior Colliculus.","date":"2010","source":"Experimental neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/22110341","citation_count":3,"is_preprint":false},{"pmid":"38629918","id":"PMC_38629918","title":"LGP2 Facilitates Bacterial Escape through Binding Peptidoglycan via EEK Motif and Suppressing NOD2-RIP2 Axis in Cyprinidae and Xenocyprididae Families.","date":"2024","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/38629918","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.12.23.629471","title":"Ephrin-A5 or EphA7 stimulation is anti-proliferative for human rhabdomyosarcoma<i>in vitro</i>","date":"2024-12-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.23.629471","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10518,"output_tokens":3059,"usd":0.038719},"stage2":{"model":"claude-opus-4-6","input_tokens":6452,"output_tokens":2629,"usd":0.146978},"total_usd":0.185697,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1991,\n      \"finding\": \"EphA8 (Eek) encodes a receptor protein-tyrosine kinase of the Eph subclass, containing all conserved catalytic domain residues, most abundantly expressed in brain.\",\n      \"method\": \"cDNA cloning, Northern blot, sequence analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — original identification with molecular characterization, single lab\",\n      \"pmids\": [\"1648701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"EphA8 loss-of-function in mice causes aberrant axonal projections: tectal neurons in the superior colliculus fail to reach contralateral inferior colliculus targets and form an abnormal ipsilateral tract to cervical spinal cord, establishing EphA8 as required for axonal pathfinding.\",\n      \"method\": \"EphA8 knockout mice, axonal tracing, retrograde labeling\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic knockout with defined neuroanatomical phenotype, replicated by multiple tracing methods\",\n      \"pmids\": [\"9214628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"EphA8 (Eek) receptor can be activated by at least three GPI-linked ephrin ligands: Elf-1/Cek7-L, Ehk1-L/Efl-2/Lerk3, and AL-1/RAGS, as demonstrated by binding and receptor phosphorylation assays.\",\n      \"method\": \"Fc-fusion chimeric ligand binding assays, receptor phosphorylation in NIH3T3 cells\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding and phosphorylation assays, single lab\",\n      \"pmids\": [\"9053851\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"EphA8 has two major autophosphorylation sites, Tyr-615 (juxtamembrane) and Tyr-838 (kinase domain); Tyr-838 phosphorylation is required for catalytic activity, while phospho-Tyr-615 mediates preferential binding to the Fyn SH2 domain over Src and RasGAP SH2 domains. EphA8 and Fyn physically associate in intact cells, and Fyn is a downstream target mediating EphA8 effects on cell adhesion.\",\n      \"method\": \"2D phosphopeptide mapping, in vitro kinase assays, site-directed mutagenesis, in vitro SH2 binding, co-immunoprecipitation, dominant-negative Fyn overexpression\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro kinase assay with mutagenesis, in vitro binding, and in-cell co-IP with functional validation\",\n      \"pmids\": [\"10498895\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"EphA8 binds ephrin-A1 and ephrin-A4 (in addition to previously known ephrin-A2, -A3, -A5) but not transmembrane ephrin-B ligands, confirming EphA8 as a GPI-linked ephrin-dependent receptor tyrosine kinase.\",\n      \"method\": \"Fc-fusion chimeric ligand binding assays, receptor tyrosine phosphorylation in NIH3T3 fibroblasts\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding and phosphorylation assays, single lab\",\n      \"pmids\": [\"10515610\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"EphA8 enhances cell adhesion to fibronectin via α5β1 and β3 integrins through a tyrosine kinase-independent mechanism that requires ephrin-A binding to the extracellular domain and the juxtamembrane segment of the intracellular domain. The p110γ isoform of PI3-kinase associates with EphA8 via the juxtamembrane segment and mediates integrin activation.\",\n      \"method\": \"Cell adhesion assays, kinase-inactive mutants, domain deletion mutants, wortmannin inhibition, in vitro binding, co-immunoprecipitation, dominant-negative p110γ overexpression\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — multiple mutants, in vitro binding, pharmacological inhibition, and dominant-negative approach in two cell lines\",\n      \"pmids\": [\"11416136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"EphA8 phosphorylates and activates low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) in vitro, and activated LMW-PTP in turn dephosphorylates EphA8, suggesting a feedback-control mechanism for EphA8 autokinase activity.\",\n      \"method\": \"In vitro kinase assay, phosphatase activity assay\",\n      \"journal\": \"Journal of biochemistry and molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution, single lab, no in-cell validation\",\n      \"pmids\": [\"12787484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Ligand-stimulated EphA8 signaling requires p110γ PI3-kinase activity to promote cell migration on fibronectin; a lipid kinase-inactive p110γ dominantly suppresses ephrin-A5-stimulated PI3-kinase activity and migration, in a manner independent of EphA8 tyrosine kinase activity.\",\n      \"method\": \"Ephrin-A5-Fc stimulation, lipid kinase-inactive dominant-negative p110γ, cell migration assay on fibronectin\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — dominant-negative approach with functional migration readout, corroborates prior co-IP data from same group\",\n      \"pmids\": [\"12681484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"EphA8 induces neurite outgrowth in NG108-15 neuronal cells in a ligand-independent manner, requiring the tyrosine kinase domain but not tyrosine kinase activity, through sustained MAPK activation that drives MAPK relocalization from cytoplasm to nucleus.\",\n      \"method\": \"Deletion mutants, kinase-inactive mutants, pharmacological inhibitors, MAPK activity assay, subcellular fractionation/immunofluorescence in NG108-15 cells\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple mutants and inhibitors with defined cellular phenotype, single lab\",\n      \"pmids\": [\"15782114\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Upon ephrin-A5 stimulation, PTB domain-containing Anks family proteins AIDA-1b and Odin associate with the juxtamembrane domain of EphA8 in a tyrosine kinase-independent manner. Odin acts as a physiologically relevant scaffold for EphA8 signaling; its knockdown diminishes ephrin-A5-induced inhibition of cell migration and neurite retraction.\",\n      \"method\": \"Co-immunoprecipitation, PTB domain pulldown, siRNA knockdown, cell migration assay, dominant-negative PTB domain overexpression\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP, domain mapping, siRNA knockdown with defined functional phenotype\",\n      \"pmids\": [\"17875921\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"EphA8 undergoes clathrin-mediated endocytosis upon ephrin-A5 stimulation; the juxtamembrane region of EphA8 is required for endocytosis and for association with Tiam-1 (a Rac-specific GEF). Tiam-1 knockdown impairs endocytosis of EphA8-ephrin-A5 complexes and reduces Rac activation.\",\n      \"method\": \"EphA8 deletion mutants, clathrin-mediated endocytosis assay, co-immunoprecipitation with Tiam-1, Rac activity assay, Tiam-1 siRNA knockdown\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — domain mapping, co-IP, siRNA knockdown with functional readouts, single lab\",\n      \"pmids\": [\"20496116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"RINL (a Rab5 subfamily GEF) interacts with Odin and forms a ternary complex with EphA8. RINL expression reduces EphA8 protein levels in a manner dependent on both RINL GEF activity and Odin interaction, placing RINL in the EphA8 degradation pathway via Rab5-mediated trafficking.\",\n      \"method\": \"Co-immunoprecipitation, GEF activity assay (GTP-bound Rab measurement), RINL knockdown, overexpression in HeLa cells\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — co-IP, GEF assay, and knockdown with EphA8 level readout, single lab\",\n      \"pmids\": [\"22291991\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"EphA8-Fc ectopic expression in transgenic embryos induces caspase-dependent apoptosis of ephrin-A5-expressing neural epithelial cells via reverse signaling through ephrin-As, causing reduced brain size.\",\n      \"method\": \"Transgenic embryo expression of EphA8-Fc, in vitro neuroepithelial cell culture with EphA8-Fc, caspase inhibitor assays, apoptosis quantification\",\n      \"journal\": \"Developmental neurobiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo transgenic and in vitro culture with caspase inhibitor functional validation, single lab\",\n      \"pmids\": [\"23696555\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EphA8 is a GPI-linked ephrin-A-activated receptor tyrosine kinase that signals through both kinase-dependent (autophosphorylation at Tyr-838 enabling Tyr-615 phosphorylation and Fyn recruitment; sustained MAPK activation for neurite outgrowth) and kinase-independent mechanisms (juxtamembrane segment recruits p110γ PI3-kinase to promote integrin-mediated cell adhesion and migration, and scaffolds Odin/Anks proteins for migration inhibition), undergoes Tiam-1-regulated clathrin-mediated endocytosis with Rab5/RINL-dependent degradation, and is required in vivo for axonal pathfinding in the developing superior colliculus.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"EphA8 is a receptor tyrosine kinase of the Eph family that transduces GPI-linked ephrin-A signals to regulate axonal pathfinding, cell adhesion, migration, and neurite dynamics during neural development. EphA8 autophosphorylates at Tyr-838 (required for catalytic activity) and Tyr-615 (which recruits Fyn via its SH2 domain), and signals through both kinase-dependent sustained MAPK activation for neurite outgrowth and kinase-independent recruitment of p110γ PI3-kinase and Odin/AIDA-1b scaffolds via its juxtamembrane segment to control integrin-mediated adhesion and migration [PMID:10498895, PMID:11416136, PMID:15782114, PMID:17875921]. Ligand-stimulated EphA8 undergoes Tiam-1-regulated clathrin-mediated endocytosis and Rab5/RINL-dependent degradation [PMID:20496116, PMID:22291991]. Loss of EphA8 in mice causes aberrant axonal projections from the superior colliculus, establishing its requirement for axonal pathfinding in vivo [PMID:9214628].\",\n  \"teleology\": [\n    {\n      \"year\": 1991,\n      \"claim\": \"Identification of EphA8 (Eek) as a brain-enriched Eph-family receptor tyrosine kinase established the gene's molecular identity and tissue expression context.\",\n      \"evidence\": \"cDNA cloning, Northern blot, and sequence analysis from mouse cDNA\",\n      \"pmids\": [\"1648701\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional data on kinase activity or ligand specificity\", \"Expression data limited to Northern blot without cellular resolution\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Knockout mice revealed that EphA8 is required for axonal pathfinding in the superior colliculus, with tectal neurons forming aberrant ipsilateral tracts to cervical spinal cord instead of reaching contralateral targets, establishing the first in vivo function.\",\n      \"evidence\": \"EphA8 knockout mice with axonal tracing and retrograde labeling\",\n      \"pmids\": [\"9214628\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream signaling pathways mediating the pathfinding phenotype unknown\", \"Whether phenotype is cell-autonomous was not addressed\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Ligand specificity was defined: EphA8 binds multiple GPI-linked ephrin-A ligands (ephrin-A1–A5) but not transmembrane ephrin-B ligands, classifying it as an EphA receptor.\",\n      \"evidence\": \"Fc-fusion ligand binding assays and receptor phosphorylation in NIH3T3 cells across two studies\",\n      \"pmids\": [\"9053851\", \"10515610\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative binding affinities for individual ephrin-A ligands not quantified\", \"In vivo relevance of specific ephrin-A partners not resolved\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Mapping of autophosphorylation sites (Tyr-838 for catalytic activation, Tyr-615 for Fyn SH2 recruitment) and demonstration of EphA8–Fyn physical association established the kinase-dependent signaling axis controlling cell adhesion.\",\n      \"evidence\": \"2D phosphopeptide mapping, site-directed mutagenesis, in vitro SH2 binding, co-immunoprecipitation, dominant-negative Fyn\",\n      \"pmids\": [\"10498895\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Fyn substrates downstream of EphA8 not identified\", \"Structural basis of SH2 selectivity for Fyn over Src/RasGAP unknown\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"A kinase-independent signaling arm was uncovered: the juxtamembrane segment recruits p110γ PI3-kinase to activate α5β1/β3 integrins for fibronectin adhesion and migration, independent of EphA8 catalytic activity.\",\n      \"evidence\": \"Kinase-inactive and domain-deletion mutants, wortmannin inhibition, co-immunoprecipitation, dominant-negative p110γ in two cell lines\",\n      \"pmids\": [\"11416136\", \"12681484\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding interface between juxtamembrane segment and p110γ not mapped\", \"How p110γ lipid kinase products activate integrins remains unclear\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"EphA8 drives neurite outgrowth via sustained MAPK activation and nuclear MAPK translocation, requiring the kinase domain but not kinase activity, revealing a scaffolding function of the kinase domain.\",\n      \"evidence\": \"Deletion and kinase-inactive mutants, pharmacological MAPK inhibitors, subcellular fractionation in NG108-15 neuronal cells\",\n      \"pmids\": [\"15782114\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How the inactive kinase domain scaffolds MAPK activation is mechanistically undefined\", \"Ligand-independent context limits physiological extrapolation\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Odin and AIDA-1b were identified as PTB-domain scaffolds recruited to the EphA8 juxtamembrane region in a kinase-independent manner; Odin knockdown diminished ephrin-A5-induced inhibition of migration and neurite retraction, establishing Odin as a physiological effector.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, PTB domain pulldown, siRNA knockdown with migration and neurite retraction assays\",\n      \"pmids\": [\"17875921\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Odin downstream targets not identified\", \"How Odin and p110γ share the juxtamembrane binding site is unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"EphA8 was shown to undergo clathrin-mediated endocytosis upon ephrin-A5 stimulation, regulated by Tiam-1 (a Rac GEF) binding to the juxtamembrane region, linking receptor trafficking to Rac activation.\",\n      \"evidence\": \"EphA8 deletion mutants, clathrin endocytosis assay, Tiam-1 co-immunoprecipitation and siRNA knockdown, Rac activity assay\",\n      \"pmids\": [\"20496116\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct Tiam-1 binding site on juxtamembrane region not mapped\", \"Functional consequence of impaired endocytosis on downstream signaling not tested in neurons\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"RINL, a Rab5-family GEF, was placed in the EphA8 degradation pathway: RINL forms a ternary complex with Odin and EphA8, and RINL GEF activity reduces EphA8 protein levels via Rab5-dependent trafficking.\",\n      \"evidence\": \"Co-immunoprecipitation, GEF activity assay, RINL knockdown and overexpression in HeLa cells\",\n      \"pmids\": [\"22291991\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Lysosomal versus proteasomal route of EphA8 degradation not distinguished\", \"In vivo relevance of RINL-mediated EphA8 turnover not tested\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"EphA8 ectodomain (EphA8-Fc) was shown to trigger caspase-dependent apoptosis in ephrin-A5-expressing neuroepithelial cells via reverse signaling, causing reduced brain size in transgenic embryos.\",\n      \"evidence\": \"Transgenic embryo EphA8-Fc expression, in vitro neuroepithelial culture with caspase inhibitors, apoptosis quantification\",\n      \"pmids\": [\"23696555\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Intracellular pathway from ephrin-A5 reverse signal to caspase activation not defined\", \"Contribution of reverse versus forward signaling to the brain size phenotype not fully separated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No structural model of EphA8 signaling complexes exists, the mechanism by which the kinase domain scaffolds MAPK independently of catalytic activity is unresolved, and the in vivo signaling pathways responsible for the superior colliculus axon guidance phenotype remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No crystal structure of EphA8 intracellular domain or its complexes\", \"Cell-type-specific conditional knockouts needed to resolve cell-autonomous functions\", \"Integration of kinase-dependent and kinase-independent pathways in vivo not addressed\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 3, 6]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [5, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2, 5, 10]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [10, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 5, 7, 8, 9]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 12]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"FYN\",\n      \"PIK3CG\",\n      \"ANKS1A\",\n      \"ANKS1B\",\n      \"TIAM1\",\n      \"RINL\",\n      \"EFNA5\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}