Affinage

EPHA7

Ephrin type-A receptor 7 · UniProt Q15375

Length
998 aa
Mass
112.1 kDa
Annotated
2026-06-09
84 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPHA7 is an ephrin-A receptor tyrosine kinase that guides topographic axon and tissue patterning during development and acts as a context-dependent regulator of cell survival and differentiation (PMID:16301174, PMID:16615124, PMID:32314958). The gene produces a full-length kinase-active isoform (TK+) and a truncated isoform lacking the kinase domain (TK-) that are distributed in distinct neuronal compartments and exert opposing actions: the kinase-active isoform mediates repulsive ephrin-A signaling to control corticothalamic projection topography, restrict dendritic growth, and regulate cortical domain formation, whereas the truncated isoform dimerizes with and dampens phosphorylation of the full-length receptor, behaving as a dominant-negative modulator that can instead increase dendritic spine density (PMID:16615124, PMID:10640696, PMID:33275600). EphA7 signaling restricts dendritic extent through Src and Tsc1 and stabilizes GABAergic inhibitory synaptic terminals through an mTOR–gephyrin–collybistin axis essential for hippocampal LTP and learning (PMID:24707048, PMID:27405707). In peripheral tissues EphA7 directs nephric duct insertion via ephrin-B2, spiral ganglion neuron innervation of cochlear hair cells through ERK1/2, and skeletal muscle differentiation by promoting myoblast apoptosis and terminal commitment through juxtacrine contact (PMID:25139858, PMID:26178595, PMID:32314958). Ligand-dependent receptor phosphorylation underlies a tumor-suppressive function in which EphA7 induces apoptosis via Bax/caspase-3/Bcl-2 modulation and dephosphorylation of Akt, and a kinase-dead or cytoplasmic-domain-deleted receptor loses this activity (PMID:29022918). Beyond its kinase signaling, EphA7 forms a death-inducing complex with TNFR1 upon ephrinA5 stimulation to trigger caspase-dependent apoptosis, and serves as a cell-surface receptor for KSHV gH/gL-mediated viral entry and transmission (PMID:23657875, PMID:31118261). EphA7 transcription is tightly controlled by HOXA13/HOXD13, STAT3, SP1/DNMT1, and Satb2, and is silenced by BMI-1-directed H3K27 trimethylation and promoter CpG methylation (PMID:16314414, PMID:17304517, PMID:37738252, PMID:34546353, PMID:27533460, PMID:40258813).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Established that EphA7 is expressed as two functionally distinct isoforms with separate subcellular distributions, framing the gene as more than a single repulsive receptor.

    Evidence Isoform-specific antibody immunohistochemistry in adult mouse brain

    PMID:10640696

    Open questions at the time
    • No functional rescue distinguishing isoform roles in this study
    • Dominant-negative model inferred from localization, not tested biochemically
  2. 2005 High

    Demonstrated that EphA7 on cortical axons sets corticothalamic projection topography, defining its developmental axon-guidance role in vivo.

    Evidence In utero electroporation mis-expression and axon tracing in mouse cortex

    PMID:16301174

    Open questions at the time
    • Ligand and downstream effectors of the topographic signal not identified here
    • Gain-of-function only
  3. 2005 High

    Identified EphA7 as a direct transcriptional target of paralog-group-13 Hox proteins, linking limb patterning programs to its expression.

    Evidence In vivo ChIP, promoter reporter, and binding-site mutagenesis in mouse limb

    PMID:16314414

    Open questions at the time
    • Functional consequence of Hox-driven EphA7 in limb morphogenesis not dissected
  4. 2006 High

    Showed that the TK+/TK- isoform ratio shifts across cortical development and that EphA7 controls ephrin-A5 distribution and cortical area size, establishing it as a regulator of cortical domain formation.

    Evidence EphA7-/- mouse analysis with isoform expression profiling and cortical area measurements

    PMID:16615124

    Open questions at the time
    • Mechanism by which isoform ratio is regulated unknown
    • Direct measurement of repulsive signaling strength absent
  5. 2007 High

    Extended Hox control to genital tubercle vasculature and revealed leukemogenic fusion proteins can hijack the EphA7 promoter, showing context-specific transcriptional regulation tied to ERK signaling.

    Evidence ChIP, transcriptional activation assays, Hoxa13 mutant mice, and ALL1-fusion knockdown with ERK/apoptosis readouts

    PMID:17304517 PMID:17726105

    Open questions at the time
    • Whether EphA7 kinase activity drives ERK in leukemic cells not resolved
    • Direct vs indirect ERK coupling unclear
  6. 2013 High

    Revealed a kinase-independent death pathway in which ephrinA5-bound EphA7 recruits TNFR1 to drive caspase-dependent apoptosis.

    Evidence EphrinA5-Fc pull-down, co-IP, and TNFR1 domain-deletion mutants with apoptosis assays

    PMID:23657875

    Open questions at the time
    • Physiological setting of the EphA7-TNFR1 complex not defined
    • Stoichiometry of the multiprotein complex unknown
  7. 2014 High

    Defined the downstream effectors (Src, Tsc1) by which EphA7 restricts dendrite growth and later promotes spine maturation, and showed EphA7/EphA4 from pericloacal mesenchyme signal via ephrin-B2 for nephric duct insertion.

    Evidence EphA7 KO with patterned substrates, electrophysiology, and compound/conditional knockout genetics

    PMID:24707048 PMID:25139858

    Open questions at the time
    • How a single receptor switches from growth-restricting to spine-maturing not mechanistically resolved
    • Direct biochemical link to ephrin-B2 reverse signaling inferred genetically
  8. 2015 High

    Placed EphA7 upstream of ERK1/2 in spiral ganglion neuron innervation, generalizing its role in directed neuronal connectivity to the auditory system.

    Evidence EphA7 KO mice, SGN culture knockdown, ERK inhibitors, and Prkg1 knockout with electrophysiology

    PMID:26178595

    Open questions at the time
    • Ligand identity for SGN signaling not specified
    • Coupling of EphA7 to ERK1/2 mechanistically indirect
  9. 2016 High

    Connected EphA7 to inhibitory synapse stability through an mTOR-gephyrin-collybistin axis, to HSPC adhesion/migration via Rac1, and revealed paralog-specific functions versus EphA4.

    Evidence In vivo knockdown with LTP/behavior, gephyrin co-IPs, ephrinA5-Fc HSPC assays with Rac1 inhibition, and comparative ligand-binding KO analysis

    PMID:26587807 PMID:27405707 PMID:27988259

    Open questions at the time
    • How EphA7 activation engages mTOR not biochemically traced
    • HSPC findings are Medium-confidence single-lab
  10. 2016 Medium

    Identified BMI-1 epigenetic silencing and an EPHA10 heterocomplex, broadening regulatory inputs and receptor-receptor interactions.

    Evidence BMI-1 overexpression with chromatin-modification analysis and EPHA7-EPHA10 co-IP/co-localization

    PMID:27533460 PMID:27566654

    Open questions at the time
    • BMI-1 study lacks detailed method reporting
    • EPHA10 interaction is single-lab co-IP without functional readout
  11. 2017 High

    Established that ligand-dependent receptor phosphorylation is required for EphA7 tumor suppression via PI3K/Akt dephosphorylation and Bax/caspase-3/Bcl-2 modulation, and identified CLDN6 as a substrate in renal tubule morphogenesis.

    Evidence Phospho-site mutagenesis with xenograft/apoptosis assays in prostate cancer; Xenopus morpholino with CLDN6 binding and phosphorylation assays

    PMID:29022918 PMID:29223398

    Open questions at the time
    • Direct kinase substrates linking phosphorylation to Akt dephosphorylation unknown
    • CLDN6 work is Medium-confidence single-lab
  12. 2019 High

    Showed EphA7 is a functional receptor for KSHV gH/gL viral entry, defined Zfp422 enhancer control of EphA7-driven myoblast apoptosis, and identified EphA7 as a multipotent pericyte marker.

    Evidence Recombinant gH/gL precipitation with CRISPR KO infection assays; ChIP-Seq with Zfp422 KO and C2C12 differentiation; FACS isolation and ischemia transplantation

    PMID:31118261 PMID:31471947 PMID:31685980

    Open questions at the time
    • Whether viral receptor function requires kinase activity untested
    • Pericyte marker role is Medium-confidence correlative isolation
  13. 2020 High

    Demonstrated EphA7 drives skeletal muscle terminal differentiation by juxtacrine signaling and confirmed full-length and truncated isoforms physically interact to oppose each other in cortical dendrite development.

    Evidence EphA7 KO mice with ECD rescue and muscle analysis; isoform overexpression, co-IP, and in vivo rapamycin epistasis; Nicalin IP/MS and fractionation

    PMID:32314958 PMID:32914261 PMID:33275600

    Open questions at the time
    • mTOR-dependence switch across development not biochemically mapped
    • Nicalin/sEphA7 ER trafficking role is Medium-confidence single-lab
  14. 2021 High

    Provided structural insight into how kinase-domain mutations alter hinge, DFG motif, and nucleotide-binding conformations relevant to catalytic regulation.

    Evidence X-ray crystallography of EphA7 kinase-domain point mutants

    PMID:34186436

    Open questions at the time
    • Catalytic activity of mutants not directly measured
    • Functional consequence in cells not tested
  15. 2023 Medium

    Defined STAT3 as a direct activator of EphA7 required for STAT3-driven proliferation in esophageal squamous cell carcinoma, contrasting with its tumor-suppressive role elsewhere.

    Evidence ChIP, truncated-promoter luciferase, STAT3 inhibition, IL-6 stimulation, and siRNA with RNA-seq

    PMID:37738252

    Open questions at the time
    • Why EphA7 is pro-proliferative in ESCC versus suppressive in prostate not reconciled
    • Single-lab
  16. 2025 Medium

    Expanded the regulatory and effector network with m6A stabilization by METTL3, a tRNA-derived fragment targeting EphA7 mRNA in Alzheimer's models, SP1/DNMT1 demethylation control, and divergent ephrin-A2 usage in rhabdomyosarcoma.

    Evidence METTL3 epistasis with xenograft; dual-luciferase tRF targeting with ERK1/2-p70S6K dissection in APP/PS1 mice; CRISPR promoter pull-down with dCas9-Tet1 demethylation; Fc-chimera binding/proliferation assays in hRMS

    PMID:40258813 PMID:40375351 PMID:40426233 PMID:40586624

    Open questions at the time
    • Biochemical site of m6A on EPHA7 not confirmed
    • Ligand-specificity switch mechanism in tumors unresolved
    • All single-lab Medium-confidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor reconciles opposing tumor-suppressive (Akt dephosphorylation, apoptosis) and tumor-promoting (STAT3-driven proliferation) outcomes, and how isoform ratio, ligand identity, and phosphorylation state are coordinated to select among repulsion, apoptosis, differentiation, and viral entry, remains unresolved.
  • No unified model linking phosphorylation-dependent and kinase-independent functions
  • Context-determinants of pro- vs anti-tumor signaling unknown
  • In vivo substrate repertoire of the kinase undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3
Partners
CLDN6EFNA2EFNA5EFNB2EPHA10NCLNTNFR1
Complex memberships
EphA7-EPHA10 receptor heterocomplexEphA7-TNFR1 ephrinA5-induced death complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 EphA7-mediated signaling on neocortical axons controls the within-nucleus topography of corticothalamic (CT) projections in the thalamus, as demonstrated by in utero electroporation-mediated mis-expression of EphA7 in cortical neurons, which disrupted CT topography without altering thalamocortical projection topography. In utero electroporation-mediated gene transfer, axon tracing Neuron High 16301174
2005 HOXA13 and HOXD13 directly bind to cis-regulatory sites in the EphA7 promoter in vivo (ChIP in developing mouse limbs) and activate EphA7 transcription; mutation of the HOXA13/HOXD13 binding site abolishes activation, establishing EphA7 as a direct downstream target of paralog group 13 Hox proteins during limb development. ChIP in developing mouse limbs, promoter reporter assays, mutagenesis of binding sites The Journal of biological chemistry High 16314414
2006 EphA7 produces two isoforms from the same gene: a full-length receptor tyrosine kinase (TK+) and a truncated isoform lacking the kinase domain (TK-). The proportions of these isoforms shift during cortical development from a more repulsive (TK+ dominant) mix embryonically to a more permissive (TK- dominant) mix postnatally; in EphA7-/- mice, the distribution of ephrin-A5 is altered and the somatosensory cortex area is reduced, establishing EphA7 as a regulator of cortical domain formation and ephrin-A5 distribution. EphA7-/- mouse analysis, RNA expression profiling, in vivo functional studies, cortical area measurements The Journal of comparative neurology High 16615124
1999 EphA7 encodes both a TK+ (full-length) and a TK- (kinase-domain-lacking) isoform with strikingly different distributions in adult mouse brain: TK+ immunoreactivity is on neuropil/axonal arborizations throughout telencephalon, while TK- is conspicuous on cell bodies and proximal dendrites of specific neuronal types; the TK- isoform may act as a dominant-negative antagonist to ensure TK+ responds only to signals at growing axon/dendrite tips. Isoform-specific antibodies, immunohistochemistry in adult mouse brain Brain research. Molecular brain research Medium 10640696
2007 ALL1/AF4 and ALL1/AF9 fusion proteins directly occupy the EphA7 promoter (ChIP) and transcriptionally upregulate EphA7 in leukemic cells; siRNA-mediated knockdown of ALL1/AF4 in t(4;11) cells downregulates EphA7; EphA7 upregulation is accompanied by ERK phosphorylation, and ERK inhibition induces apoptosis specifically in t(4;11) leukemic cells. ChIP, siRNA knockdown, quantitative RT-PCR, ERK phosphorylation assay, apoptosis assay Proceedings of the National Academy of Sciences of the United States of America High 17726105
2013 EphA7 interacts with death receptor TNFR1 to form a multi-protein complex upon ephrinA5 stimulation; pull-down with biotinylated ephrinA5-Fc confirmed ephrinA5-EphA7 complexes recruit TNFR1; both the internalization motif and death domain of TNFR1 are required for interaction with the intracytoplasmic region of EphA7; this complex is essential for caspase-dependent apoptotic cell death. Pull-down assay with biotinylated ephrinA5-Fc, co-immunoprecipitation, immunocytochemistry, domain deletion mutants Molecules and cells High 23657875
2014 EphA7 signaling in cortical neurons restricts dendritic extent (via Src and Tsc1 as downstream mediators) and later promotes dendritic spine maturation and synaptic function; EphA7-/- neurons have longer, more complex dendrites, while EphA7 overexpression shortens dendrites; electrophysiological maturation of pyramidal neurons is delayed in EphA7-null cultures. Patterned substrates, EphA7 knockout mice, in vitro overexpression, electrophysiology, in vivo perturbation Proceedings of the National Academy of Sciences of the United States of America High 24707048
2014 EphA4 and EphA7 are expressed in the pericloacal mesenchyme and are required for nephric duct insertion into the cloaca; Epha4-/-;Epha7+/- and double knockout mice show distal ureter malformations and failure of ND-cloaca fusion; conditional deletion of ephrin-B2 from the nephric duct phenocopies this, indicating that EphA4/EphA7 from pericloacal mesenchyme signal via ephrin-B2 to mediate ND insertion. Compound knockout mice, conditional ephrin-B2 deletion, embryo analysis Development (Cambridge, England) High 25139858
2016 EphA7 receptor tyrosine kinase is required for stabilization of basket cell inhibitory synaptic terminals on proximal dendritic and somatic compartments of dentate gyrus granule cells; EphA7 deficiency destabilizes GABAergic synapses and impairs LTP and hippocampal learning; EphA7 overexpression or ephrin stimulation induces gephyrin clustering in an mTOR-dependent manner, and activated mTOR releases its interaction with gephyrin while enhancing gephyrin-collybistin interaction. Lentiviral knockdown in adult rats, electrophysiology (LTP), behavior, gephyrin clustering assay, co-immunoprecipitation (gephyrin-mTOR, gephyrin-collybistin) Scientific reports High 27405707
2016 EphA7 forward signaling via ephrinA5 in human hematopoietic stem and progenitor cells (HSPCs) promotes colony formation, adhesion, and migration through Rac1 activation and upregulation of WAVE1; blocking EphA7 activation reduces HSPC adhesion and migration; Rac1 inhibition abolishes ephrinA5-mediated HSPC adhesion and migration. EphrinA5-Fc stimulation, functional blocking peptides, long-term culture-initiating cell assays, adhesion/migration assays, Rac1 inhibitor, gene/protein expression analysis Experimental hematology Medium 27988259
2017 Ligand-dependent EphA7 signaling suppresses prostate cancer tumor growth and induces apoptosis via increased Bax, elevated caspase-3 activity, reduced Bcl-2, and dephosphorylation of Akt (PI3K/Akt pathway); EphA7 variants lacking the cytoplasmic domain or with a phosphorylation-inhibiting point mutation have no tumor suppressive effect in vivo or in vitro, demonstrating that receptor phosphorylation is essential. Site-directed mutagenesis, overexpression in PCa cells, in vivo tumor xenograft, apoptosis assays, western blotting for Bax/Bcl-2/Akt phosphorylation Cell death & disease High 29022918
2019 Endogenously expressed EphA7 in BJAB B cells functions as a receptor for KSHV gH/gL glycoprotein complex and is critical for cell-to-cell transmission of KSHV; endogenous EphA7 was precipitated from BJAB cell lysate using recombinant gH/gL; EphA7 knockout significantly reduced KSHV transmission; EphA7 also functions as receptor for cell-free infection by rhesus monkey rhadinovirus. Protein precipitation with recombinant gH/gL, CRISPR/Cas9 knockout, viral infection assay Journal of virology High 31118261
2019 Zfp422 transcription factor directly binds a 169-bp upstream enhancer region of EphA7 (identified by ChIP-Seq) and regulates EphA7 expression; EphA7 expression maintains proper myoblast apoptosis required for differentiation; knockdown of EphA7 or deletion of Zfp422 inhibits myoblast apoptosis and impairs skeletal muscle differentiation and fusion. ChIP-Seq, Zfp422 conditional knockout in skeletal muscle, EphA7 siRNA knockdown, C2C12 differentiation assays Cell death and differentiation High 31685980
2020 EphA7 is expressed on terminally differentiated myocytes during embryonic/fetal myogenesis and nascent myofibers during regeneration; EphA7-/- mice have fewer, smaller myofibers at birth with fewer myonuclei; EphA7 promotes commitment of adjacent myoblasts to terminal differentiation via juxtacrine (cell-cell contact) signaling; exogenous EphA7 extracellular domain rescues the null phenotype in vitro. EphA7-/- mouse analysis, exogenous EphA7-ECD treatment, in vitro differentiation assays, in vivo muscle analysis eLife High 32314958
2020 EphA7 full-length (EphA7-FL) and truncated isoform (EphA7-T1, lacking kinase domain) have opposing effects on cortical dendrite development: EphA7-FL inhibits dendritic growth and spine formation, while EphA7-T1 increases spine density; downstream signaling shifts with development (mTOR-dependent early, mTOR-independent late); EphA7-FL and EphA7-T1 directly interact in cultured cells, reducing EphA7-FL phosphorylation. Isoform overexpression in cultured neurons, in vivo rapamycin treatment, co-immunoprecipitation of isoforms, dendritic morphometry PloS one High 33275600
2016 Physical interaction between kinase-deficient EPHA10 and kinase-sufficient EPHA7 was demonstrated by co-immunoprecipitation; both receptors co-localize on the cell surface and exist as a complex in the cytoplasm and nucleus; expression of EPHB6 in MDA-MB-231 cells alters the co-localization pattern, abolishing nuclear co-localization. Co-immunoprecipitation, immunocytochemistry, stable EPHB6 transfection Cancer genomics & proteomics Medium 27566654
2015 EphA7 is required for normal spiral ganglion neuron (SGN) innervation of cochlear hair cells; EphA7 deletion reduces inner radial bundles, ribbon synapses on inner hair cells, and overall auditory nerve activity; knockdown of EphA7 in SGNs diminishes SGN fiber outgrowth in vitro; ERK1/2 inhibition or Prkg1 knockout also reduces SGN fibers, placing ERK1/2 downstream of EphA7 signaling. EphA7 knockout mice, siRNA knockdown in SGN cultures, ERK inhibitors, Prkg1 knockout, immunohistochemistry, electrophysiology Developmental neurobiology High 26178595
2007 HOXA13 directly binds cis-regulatory elements in the EphA6 and EphA7 promoters in vivo (GT chromatin immunoprecipitation); HOXA13 activates EphA7 gene expression through these regulatory elements in vitro; Hoxa13-/- mice show reduced EphA7 expression in the genital tubercle vascular endothelia. ChIP from genital tubercle tissue, in vitro transcriptional activation assays, Hoxa13 mutant mice Developmental dynamics High 17304517
2016 BMI-1 (encoded by BMI1) directly targets EphA7 in neural cells and lymphocytes, repressing it via H3K27 trimethylation and DNA methylation; BMI-1 overexpression is identified as a novel mechanism leading to EphA7 inactivation. ChIP (implied by chromatin modification analysis), BMI-1 overexpression, expression analysis Oncotarget Medium 27533460
2022 Satb2 transcription factor directly suppresses EphA7 expression in cortical neurons (ChIP and luciferase reporter assays); Satb2 conditional knockout increases EphA7 in layers II/III; overexpression of EphA7 in wild-type neurons phenocopies Satb2 knockdown (soma clumping, impaired dendritic self-avoidance); reducing EphA7 rescues Satb2-knockdown phenotypes. ChIP, luciferase reporter assay, RNA-seq, in utero electroporation (overexpression and rescue), Satb2 conditional KO mice Cerebral cortex High 34546353
2016 EphA4 and EphA7 interact differently with ligands in the developing neocortex and thalamus: EphA7 (but not EphA4) shows strong interaction with ligands in somatosensory thalamic nuclei; EphA7 affects both cortical neuronal migration and CT axon guidance, while EphA4 affects only cortical neuronal migration, demonstrating functional specificity between closely related Eph receptors. Ligand binding assays, EphA4 and EphA7 mutant mouse analysis, cortical axon tracing The Journal of comparative neurology Medium 26587807
2017 EphA7 is specifically expressed in Xenopus pronephric tubules; EphA7 knockdown causes tubule cell differentiation and morphogenesis defects; EphA7 binds and phosphorylates claudin6 (CLDN6) in cultured cells, reducing CLDN6 distribution at the cell surface; a secreted (soluble) form of EphA7 (sEphA7) antagonizes full-length EphA7. Morpholino knockdown in Xenopus, co-immunoprecipitation, phosphorylation assay in cultured cells Biochemical and biophysical research communications Medium 29223398
2016 EphA7 knockdown in Xenopus hindbrain disrupts cranial neural tube closure and inhibits apical constriction of neuroepithelial cells, leading to reduced apical F-actin accumulation; EphA7 mediates phosphorylation/activation of focal adhesion kinase (FAK) in vivo and in vitro. Morpholino knockdown in Xenopus, phalloidin staining for F-actin, FAK phosphorylation assay in vivo and in vitro Biochemical and biophysical research communications Medium 27693790
2020 Nicalin (a Nicastrin-like protein) interacts with soluble EphA7 (sEphA7) and they co-localize in the endoplasmic reticulum; Nicalin reduces the membranous level of sEphA7 while increasing insoluble cytoplasmic forms with reduced molecular weight, restricting sEphA7 entry into the ER for further modification; sEphA7 enhances EphA7-FL membrane levels and EphA7 complex formation, effects reversed by Nicalin. Immunoprecipitation/mass spectrometry, co-localization, subcellular fractionation, co-immunoprecipitation in HEK293 cells Molecular and cellular biochemistry Medium 32914261
2021 Crystal structures of EphA7 kinase domain mutants Gly656Arg, Gly656Glu, and Asp751His reveal structural changes in the hinge region and nucleotide-binding groove; Gly656Arg and Asp751His show secondary structural changes affecting open/closed kinase conformation transitions; Asp751His shows a distorted nucleotide-binding groove; differences in hydrogen bonding and hydrophobic interactions in the DFG motif suggest these mutations influence catalytic activity. X-ray crystallography of kinase domain mutants Biochemical and biophysical research communications High 34186436
2023 STAT3 transcriptionally activates EphA7 expression in ESCC cells; ChIP assay identified the -2000 to -1500 region as the key EphA7 promoter bound by STAT3; STAT3 inhibition (Stattic) reduces EphA7 protein expression while IL-6-mediated STAT3 activation upregulates it; EphA7 is required for STAT3 activation-driven cell proliferation of ESCC. ChIP assay, truncated promoter/luciferase assay, STAT3 inhibitor treatment, IL-6 stimulation, siRNA knockdown, RNA-seq Acta oncologica Medium 37738252
2025 METTL3 (the N6-adenosine-methyltransferase catalytic subunit) stabilizes EPHA7 expression through an m6A-dependent mechanism; chidamide downregulates METTL3, thereby reducing EPHA7; overexpression of EPHA7 counteracts METTL3 silencing effects, placing EPHA7 downstream of METTL3 in the same axis. METTL3 overexpression/silencing, EPHA7 overexpression rescue, in vivo xenograft, western blotting Journal of chemotherapy Medium 40586624
2025 tRFAla-AGC-3-M8 (a tRNA-derived small RNA) directly targets EphA7 mRNA (validated by dual-luciferase reporter assay); in Alzheimer's disease (APP/PS1 mice), EphA7 is upregulated in microglia and neurons, with increased ERK1/2 and p70S6K phosphorylation; EphA7 siRNA knockdown suppresses ERK1/2-p70S6K signaling, reduces tau hyperphosphorylation in neurons, and reduces M1-type polarization of microglia. Dual-luciferase reporter assay, siRNA knockdown, western blotting, immunofluorescence, APP/PS1 transgenic mice Alzheimer's research & therapy Medium 40375351
2025 In cervical cancer, SP1 and MAZ bind the EphA7 promoter (identified by CRISPR-mediated pull-down); EphA7 expression is regulated by SP1/DNMT1 (but not MAZ); 17-β-estradiol (E2) upregulates EphA7 expression through demethylation via the SP1/DNMT1 axis; CRISPR-based demethylation (dCas9-Tet1) reactivates EphA7 and suppresses tumor proliferation/invasion via PI3K/AKT signaling. CRISPR-mediated promoter pull-down, SP1/DNMT1 perturbation, dCas9-Tet1 demethylation, luciferase assay, western blotting for PI3K/AKT Cell death & disease Medium 40258813
2019 EphA7+ pericytes (CapSCs) isolated from mouse microvasculature are multipotent cells distinct from EphA7- control pericytes; EphA7 identifies a subpopulation with high multipotency, differentiating into mesenchymal, neuronal, endothelial, and pericyte lineages; transplantation of CapSCs into ischemic tissues improves blood flow recovery and vascular formation. FACS isolation, microarray identification of EphA7 as marker, in vitro multipotency assays, in vivo transplantation in hindlimb ischemia model Stem cells translational medicine Medium 31471947
2024 In human rhabdomyosarcoma (hRMS) cells, EphA7 binds and signals through ephrin-A2 (rather than ephrin-A5 as in normal muscle), and both EphA7-Fc and ephrin-A5-Fc are potent inhibitors of hRMS proliferation in vitro. Binding assays, Fc-chimera proliferation assays, expression profiling of Eph/ephrin in hRMS vs. normal muscle Skeletal muscle Medium 40426233

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Downregulation of EphA7 by hypermethylation in colorectal cancer. Oncogene 99 16007213
2019 Long noncoding RNA SNHG14 facilitates colorectal cancer metastasis through targeting EZH2-regulated EPHA7. Cell death & disease 84 31273190
2005 Dissociation of corticothalamic and thalamocortical axon targeting by an EphA7-mediated mechanism. Neuron 74 16301174
2009 Microdeletion of 6q16.1 encompassing EPHA7 in a child with mild neurological abnormalities and dysmorphic features: case report. Molecular cytogenetics 63 19664229
2009 Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features. International journal of cancer 57 18821581
2008 Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC cancer 56 18366728
2005 Hoxd13 and Hoxa13 directly control the expression of the EphA7 Ephrin tyrosine kinase receptor in developing limbs. The Journal of biological chemistry 52 16314414
2007 Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma. Human pathology 49 17669470
2006 Inhibition of EphA7 up-regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery. Journal of neuroscience research 49 16983667
2007 ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias. Proceedings of the National Academy of Sciences of the United States of America 47 17726105
2014 EphA7 signaling guides cortical dendritic development and spine maturation. Proceedings of the National Academy of Sciences of the United States of America 46 24707048
1998 The expression and regulation of chick EphA7 suggests roles in limb patterning and innervation. Development (Cambridge, England) 46 9753674
2016 MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer. International journal of molecular sciences 43 27681722
2017 Ligand-dependent EphA7 signaling inhibits prostate tumor growth and progression. Cell death & disease 38 29022918
2007 Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas. Oncogene 36 17260020
1997 Regulated expression of the Eph-related receptor tyrosine kinase Hek11 in early human B lymphopoiesis. Blood 36 9345045
1997 The expression of chick EphA7 during segmentation of the central and peripheral nervous system. Mechanisms of development 36 9431814
2021 EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers. BMC medicine 33 33526018
2006 EphA7-ephrin-A5 signaling in mouse somatosensory cortex: developmental restriction of molecular domains and postnatal maintenance of functional compartments. The Journal of comparative neurology 33 16615124
2011 EPHA7, a new target gene for 6q deletion in T-cell lymphoblastic lymphomas. Carcinogenesis 32 22114070
2019 EphA7 Functions as Receptor on BJAB Cells for Cell-to-Cell Transmission of the Kaposi's Sarcoma-Associated Herpesvirus and for Cell-Free Infection by the Related Rhesus Monkey Rhadinovirus. Journal of virology 31 31118261
1999 Distribution of the receptor EphA7 and its ligands in development of the mouse nervous system. Brain research. Molecular brain research 28 10640695
2017 MicroRNA-448 suppresses osteosarcoma cell proliferation and invasion through targeting EPHA7. PloS one 27 28604772
2015 Effect of EphA7 Silencing on Proliferation, Invasion and Apoptosis in Human Laryngeal Cancer Cell Lines Hep-2 and AMC-HN-8. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 27 25968442
2020 miR‑18a‑5p promotes melanoma cell proliferation and inhibits apoptosis and autophagy by targeting EPHA7 signaling. Molecular medicine reports 26 33236144
2019 The Diagnostic Significance of PDGF, EphA7, CCR5, and CCL5 Levels in Colorectal Cancer. Biomolecules 26 31505877
2007 HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia. Developmental dynamics : an official publication of the American Association of Anatomists 25 17304517
2019 Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis. Cell death and differentiation 23 31685980
1999 Segregation of the receptor EphA7 from its tyrosine kinase-negative isoform on neurons in adult mouse brain. Brain research. Molecular brain research 23 10640696
2022 EPHA2, EPHA4, and EPHA7 Expression in Triple-Negative Breast Cancer. Diagnostics (Basel, Switzerland) 22 35204461
2016 EphA5 and EphA7 forward signaling enhances human hematopoietic stem and progenitor cell maintenance, migration, and adhesion via Rac1 activation. Experimental hematology 22 27988259
2016 Receptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells. Scientific reports 21 27405707
2014 Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal mesenchyme. Development (Cambridge, England) 19 25139858
2020 Circulating microRNA-944 and its target gene EPHA7 as a potential biomarker for colorectal cancer. Archives of physiology and biochemistry 18 32421395
2013 EphrinA5-EphA7 complex induces apoptotic cell death via TNFR1. Molecules and cells 18 23657875
2010 Secreted form of EphA7 in lung cancer. International journal of oncology 18 20126984
2015 EphA7 regulates spiral ganglion innervation of cochlear hair cells. Developmental neurobiology 17 26178595
2022 The identification and validation of EphA7 hypermethylation, a novel biomarker, in cervical cancer. BMC cancer 16 35681118
2020 EphA7 promotes myogenic differentiation via cell-cell contact. eLife 16 32314958
2019 Capillary-resident EphA7+ pericytes are multipotent cells with anti-ischemic effects through capillary formation. Stem cells translational medicine 16 31471947
2021 microRNA-196b promotes esophageal squamous cell carcinogenesis and chemoradioresistance by inhibiting EPHA7, thereby restoring EPHA2 activity. American journal of cancer research 15 34354862
2020 MicroRNA-448/EPHA7 axis regulates cell proliferation, invasion and migration via regulation of PI3K/AKT signaling pathway and epithelial-to-mesenchymal transition in non-small cell lung cancer. European review for medical and pharmacological sciences 15 32572879
2016 EPHA7 and EPHA10 Physically Interact and Differentially Co-localize in Normal Breast and Breast Carcinoma Cell Lines, and the Co-localization Pattern Is Altered in EPHB6-expressing MDA-MB-231 Cells. Cancer genomics & proteomics 15 27566654
2015 Effects of altered ephrin-A5 and EphA4/EphA7 expression on tumor growth in a medulloblastoma mouse model. Journal of hematology & oncology 14 26345456
2022 The role of EphA7 in different tumors. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 35112312
2021 Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 13 33439936
2020 Ephrin Receptors (Eph): EphA1, EphA5, and EphA7 Expression in Uveal Melanoma-Associations with Clinical Parameters and Patient Survival. Life (Basel, Switzerland) 13 33007931
2014 Novel TBL1XR1, EPHA7 and SLFN12 mutations in a Sezary syndrome patient discovered by whole exome sequencing. Experimental dermatology 12 24689486
2014 Corticofugal projections from medial primary somatosensory cortex avoid EphA7-expressing neurons in striatum and thalamus. Neuroscience 12 24909897
2013 EphA7 expression identifies a unique neuronal compartment in the rat striatum. The Journal of comparative neurology 12 23348681
2013 Dlx5 and Msx2 regulate mouse anterior neural tube closure through ephrinA5-EphA7. Development, growth & differentiation 12 23425387
2024 Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 11 39694330
2025 tRFAla-AGC-3-M8 attenuates neuroinflammation and neuronal damage in Alzheimer's disease via the EphA7-ERK1/2-p70S6K signaling pathway. Alzheimer's research & therapy 10 40375351
2021 MicroRNA-146b-5p/EPHA7 axis regulates cell invasion, metastasis, proliferation, and temozolomide-induced chemoresistance via regulation of IRAK4/TRAF6/NF-κB signaling pathway in aggressive pituitary adenoma. Histology and histopathology 10 34746996
2019 Long noncoding RNA KCNQ1OT1 promotes proliferation, migration, and invasion in maxillary sinus squamous cell carcinoma by regulating miR-204/EphA7 axis. Journal of cellular biochemistry 10 31709597
2021 EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder. Clinical genetics 9 34176129
2020 EphA7 isoforms differentially regulate cortical dendrite development. PloS one 9 33275600
2015 EphA4 has distinct functionality from EphA7 in the corticothalamic system during mouse brain development. The Journal of comparative neurology 9 26587807
2006 EphA7 receptor is expressed differentially at chicken prosomeric boundaries. Neuroscience 9 16844303
2022 Satb2 Regulates EphA7 to Control Soma Spacing and Self-Avoidance of Cortical Pyramidal Neurons. Cerebral cortex (New York, N.Y. : 1991) 8 34546353
2020 EphA7+ perivascular cells as myogenic and angiogenic precursors improving skeletal muscle regeneration in a muscular dystrophic mouse model. Stem cell research 8 32738632
2016 The putative tumor suppressor gene EphA7 is a novel BMI-1 target. Oncotarget 8 27533460
2014 Complementary expression of EphA7 and SCO-spondin during posterior commissure development. Frontiers in neuroanatomy 8 25009468
2013 Increased expression of EphA7 in inflamed human dental pulp. Journal of endodontics 8 23321235
2012 Mining the cancer genome uncovers therapeutic activity of EphA7 against lymphoma. Cell cycle (Georgetown, Tex.) 8 22356769
2025 Targeted demethylation of the EphA7 promoter inhibits tumorigenesis via the SP1/DNMT1 and PI3K/AKT axes and improves the response to multiple therapies in cervical cancer. Cell death & disease 7 40258813
2010 [Expression of EphA7 protein in primary hepatocellular carcinoma and its clinical significance]. Zhonghua wai ke za zhi [Chinese journal of surgery] 7 20302756
2011 [Expression of EphA7 and MTDH and clinicopathological significance in the squamous cell cancer of the tongue]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 6 22246354
2024 The Role of Biomarkers in the Early Diagnosis of Gastric Cancer: A Study on CCR5, CCL5, PDGF, and EphA7. Current issues in molecular biology 5 39329983
2022 Loss of EphA7 Expression in Basal Cell Carcinoma by Hypermethylation of CpG Islands in the Promoter Region. Analytical cellular pathology (Amsterdam) 5 35103233
2017 EphA7 regulates claudin6 and pronephros development in Xenopus. Biochemical and biophysical research communications 5 29223398
2016 EphA7 modulates apical constriction of hindbrain neuroepithelium during neurulation in Xenopus. Biochemical and biophysical research communications 5 27693790
2011 Identification of EphA7 BAC clone containing a long-range dorsal midline-specific enhancer. BMB reports 4 21345310
2023 STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma. Acta oncologica (Stockholm, Sweden) 3 37738252
2020 EphA7 is required for otic epithelial homeostasis by modulating Claudin6 in Xenopus. Biochemical and biophysical research communications 3 32222280
2021 Crystal structure of clinically reported mutations Gly656Arg, Gly656Glu and Asp751His identified in the kinase domain of EphA7. Biochemical and biophysical research communications 2 34186436
2025 Knockdown of miR-204-5p promotes nerve regeneration and functional recovery after hypoxic-ischemic brain damage in neonatal rats via the Wnt2/Ephrin-A2/EphA7 pathway. Neuroreport 1 40530558
2024 Ephrin-A5 or EphA7 stimulation is anti-proliferative for human rhabdomyosarcoma in vitro. bioRxiv : the preprint server for biology 1 39763772
2016 Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat. The Journal of comparative neurology 1 26780036
2015 Identification of the 187 bp EphA7 Genomic DNA as the Dorsal Midline-Specific Enhancer of the Diencephalon and Mesencephalon. Molecules and cells 1 26537192
2025 Ephrin-A5 or EphA7 stimulation is anti-proliferative for human rhabdomyosarcoma in vitro. Skeletal muscle 0 40426233
2025 Chidamide impedes the progression of non-small cell lung cancer by inhibiting the METTL3/EPHA7 pathway. Journal of chemotherapy (Florence, Italy) 0 40586624
2025 Comprehensive analysis of Ephrin ligand and receptor expression reveals exclusive domains during nephrogenesis for epha4/epha7 and efna3. The International journal of developmental biology 0 41307306
2020 Identification of the soluble EphA7-interacting protein Nicalin as a regulator of EphA7 expression. Molecular and cellular biochemistry 0 32914261

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