Details for: EPHA7

Gene ID: 2045

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: EPHA7

Ensembl ID: ENSG00000135333

Description: EPH receptor A7

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sncg GABAergic cortical interneuron CL4023015
    CSI 27.72
    rCSI 44.58%
    PRS 91.88
  • sst GABAergic cortical interneuron CL4023017
    CSI 26.7
    rCSI 34.42%
    PRS 92.06
  • VIP GABAergic cortical interneuron CL4023016
    CSI 21.23
    rCSI 25.36%
    PRS 91.5
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 21.06
    rCSI 26.21%
    PRS 90.01
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 20.01
    rCSI 28.37%
    PRS 96.2
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 19.74
    rCSI 33.13%
    PRS 91.64
  • vascular leptomeningeal cell CL4023051
    CSI 15.72
    rCSI 27.57%
    PRS 95.44
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 15.21
    rCSI 26.86%
    PRS 91.3
  • retina horizontal cell CL0000745
    CSI 14.72
    rCSI 22.43%
    PRS 95.32
  • interneuron CL0000099
    CSI 14.04
    rCSI 28.2%
    PRS 94.7
  • L6b glutamatergic cortical neuron CL4023038
    CSI 13.74
    rCSI 42.93%
    PRS 92.05
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 13.7
    rCSI 33.31%
    PRS 89.95
  • glycinergic amacrine cell CL4030028
    CSI 13.53
    rCSI 35.25%
    PRS 93.08
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 13.52
    rCSI 15.61%
    PRS 93.06
  • epithelial cell CL0000066
    CSI 13.06
    rCSI 20.07%
    PRS 89.29
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 12.73
    rCSI 48.13%
    PRS 91.38
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 11.99
    rCSI 43.16%
    PRS 90.17
  • glioblast CL0000030
    CSI 11.96
    rCSI 19.07%
    PRS 93.2
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 11.81
    rCSI 15.15%
    PRS 95.21
  • neuron CL0000540
    CSI 10.53
    rCSI 28.05%
    PRS 89.2
  • radial glial cell CL0000681
    CSI 10.15
    rCSI 14.1%
    PRS 96.63
  • dopaminergic neuron CL0000700
    CSI 10.11
    rCSI 57.13%
    PRS 91.05
  • epithelial cell of proximal tubule CL0002306
    CSI 9.98
    rCSI 24.37%
    PRS 93.2
  • retinal bipolar neuron CL0000748
    CSI 9.42
    rCSI 17.65%
    PRS 92.91
  • peripheral nervous system neuron CL2000032
    CSI 9.29
    rCSI 12.66%
    PRS 94.06
  • neural crest cell CL0011012
    CSI 9.24
    rCSI 7.3%
    PRS 94.75
  • neural cell CL0002319
    CSI 8.93
    rCSI 33.7%
    PRS 89
  • invaginating midget bipolar cell CL4033034
    CSI 8.84
    rCSI 52.19%
    PRS 91.16
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 8.78
    rCSI 22.7%
    PRS 95.96
  • inhibitory interneuron CL0000498
    CSI 8.76
    rCSI 20.23%
    PRS 92.5
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 8.08
    rCSI 26.55%
    PRS 90.35
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 7.63
    rCSI 23.86%
    PRS 93.03
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 7.22
    rCSI 42.52%
    PRS 91.55
  • cerebral cortex endothelial cell CL1001602
    CSI 6.87
    rCSI 11.89%
    PRS 94.92
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 6.47
    rCSI 15.48%
    PRS 91.24
  • diffuse bipolar 3b cell CL4033030
    CSI 6.46
    rCSI 42.85%
    PRS 92.77
  • cerebral cortex neuron CL0010012
    CSI 6.41
    rCSI 26.1%
    PRS 92.31
  • central nervous system neuron CL2000029
    CSI 6.32
    rCSI 46.43%
    PRS 93.36
  • Schwann cell CL0002573
    CSI 5.97
    rCSI 16.96%
    PRS 95.14
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 5.37
    rCSI 13.99%
    PRS 98.05
  • amacrine cell CL0000561
    CSI 5.35
    rCSI 15.5%
    PRS 92.73
  • GABAergic neuron CL0000617
    CSI 5.21
    rCSI 17.47%
    PRS 89.4
  • cardiac neuron CL0010022
    CSI 5.09
    rCSI 16.28%
    PRS 96.45
  • regular atrial cardiac myocyte CL0002129
    CSI 4.98
    rCSI 16.04%
    PRS 94.65
  • parietal epithelial cell CL1000452
    CSI 4.95
    rCSI 13.24%
    PRS 95.01
  • cerebellar granule cell CL0001031
    CSI 4.93
    rCSI 7.25%
    PRS 94.27
  • glutamatergic neuron CL0000679
    CSI 4.75
    rCSI 9.76%
    PRS 89.82
  • rod bipolar cell CL0000751
    CSI 4.62
    rCSI 8.31%
    PRS 94.37
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 4.59
    rCSI 9.96%
    PRS 90
  • medium spiny neuron CL1001474
    CSI 4.49
    rCSI 38.64%
    PRS 92.62
  • regular ventricular cardiac myocyte CL0002131
    CSI 4.43
    rCSI 27.69%
    PRS 93.45
  • podocyte CL0000653
    CSI 4.36
    rCSI 19.38%
    PRS 97.1
  • retinal ganglion cell CL0000740
    CSI 4.33
    rCSI 9.57%
    PRS 91.83
  • OFFx cell CL4033036
    CSI 4.23
    rCSI 19.88%
    PRS 90.09
  • diffuse bipolar 4 cell CL4033031
    CSI 4.15
    rCSI 47.49%
    PRS 87.57
  • cardiac muscle cell CL0000746
    CSI 4.14
    rCSI 5.94%
    PRS 92.59
  • enteric smooth muscle cell CL0002504
    CSI 3.79
    rCSI 5.4%
    PRS 97.52
  • GABAergic amacrine cell CL4030027
    CSI 3.78
    rCSI 12.95%
    PRS 89.56
  • ON-bipolar cell CL0000749
    CSI 3.67
    rCSI 5.46%
    PRS 95.8
  • renal interstitial pericyte CL1001318
    CSI 3.57
    rCSI 9.85%
    PRS 96.43
  • mesodermal cell CL0000222
    CSI 3.24
    rCSI 3.89%
    PRS 97.4
  • diffuse bipolar 6 cell CL4033032
    CSI 2.82
    rCSI 14.81%
    PRS 90.48
  • brain vascular cell CL4023072
    CSI 2.41
    rCSI 24.99%
    PRS 93.02
  • direct pathway medium spiny neuron CL4023026
    CSI 2.22
    rCSI 53.15%
    PRS 89.28
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.2
    rCSI 52.98%
    PRS 89.06
  • glial cell CL0000125
    CSI 2.05
    rCSI 7.8%
    PRS 93.57
  • enteroglial cell CL4040002
    CSI 1.82
    rCSI 9.59%
    PRS 96.83
  • diffuse bipolar 3a cell CL4033029
    CSI 0.74
    rCSI 5.06%
    PRS 91.59
  • OFF midget ganglion cell CL4033047
    CSI 0.53
    rCSI 10.8%
    PRS 92.18
  • enteric neuron CL0007011
    CSI 0.3
    rCSI 4.42%
    PRS 96.73

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [EPHA7](/details-gene/2045) (Ephrin type-A receptor 7) is a protein-coding gene located on chromosome 6q16.1. It belongs to the Eph receptor family of receptor tyrosine kinases, which are critical mediators of cell-cell communication. The primary functions of [EPHA7](/details-gene/2045) are centered on nervous system development, particularly in processes such as '[axon guidance](/details-term/GO:0007411)', '[brain development](/details-term/GO:0007420)', and the regulation of synaptic transmission and assembly. Expression data reveals its profound significance in the central nervous system, where it is a top marker for various subtypes of [GABAergic cortical interneurons](/details-cell/CL4023015), suggesting a key role in establishing inhibitory circuits. The gene is also implicated in oncogenic processes, with studies noting its deregulation in certain leukemias and cancers ([Link](https://doi.org/10.1073/pnas.0703211104)). Clinical relevance is noted under OMIM entry [602190](https://omim.org/entry/602190). ## Cellular Roles and Expression Landscape The expression profile of [EPHA7](/details-gene/2045) underscores its central role in the nervous system. **Overall**, the gene shows the highest significance in multiple, distinct subpopulations of cortical inhibitory neurons, including [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 27.72), [sst GABAergic cortical interneurons](/details-cell/CL4023017) (CSI: 26.70), [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 21.23), and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 21.06). This consistent, high-level expression across diverse interneuron classes suggests a fundamental function in the development, migration, or synaptic targeting of these crucial regulatory cells. Beyond cortical interneurons, its significance extends to other neural cell types such as [retina horizontal cells](/details-cell/CL0000745), [glycinergic amacrine cells](/details-cell/CL4030028), and [L6b glutamatergic cortical neurons](/details-cell/CL4023038). This pattern indicates a widespread involvement in forming and maintaining complex neural circuits in both the brain and retina. Interestingly, [EPHA7](/details-gene/2045) also demonstrates significant expression in non-neuronal tissues. It is highly ranked in [kidney loop of Henle thin descending limb epithelial cells](/details-cell/CL1001111) (CSI: 20.01) and [vascular leptomeningeal cells](/details-cell/CL4023051) (CSI: 15.72), suggesting roles in renal organogenesis and the development of the brain's vasculature and meninges, respectively. This dual expression profile highlights its function as a versatile cell-cell signaling receptor deployed in multiple developmental contexts. ## Pathways and Molecular Function The molecular functions of [EPHA7](/details-gene/2045) are consistent with its role as a receptor tyrosine kinase involved in developmental signaling. Its annotated functions include '[protein tyrosine kinase activity](/details-term/GO:0004713)' and '[axon guidance receptor activity](/details-term/GO:0008046)', which are executed upon binding to its ephrin ligands. This interaction initiates downstream signaling cascades, as evidenced by its involvement in biological processes like '[protein phosphorylation](/details-term/GO:0006468)' and the '[regulation of erk1 and erk2 cascade](/details-term/GO:0070372)'. The gene's high expression in neurons is directly explained by its participation in the '[axon guidance](/details-pathway/R-HSA-422475)' and '[nervous system development](/details-pathway/R-HSA-9675108)' pathways. Specifically, it is involved in '[Eph-ephrin mediated repulsion of cells](/details-pathway/R-HSA-3928665)', a key mechanism that prevents inappropriate axonal connections and guides growth cones to their correct targets. This is further supported by annotations for '[negative regulation of synapse assembly](/details-term/GO:0051964)' and '[negative chemotaxis](/details-term/GO:0050919)', highlighting its role in establishing precise neural wiring by repelling migrating cells and developing axons from specific regions. Its presence in the '[dendrite](/details-term/GO:0030425)' and '[glutamatergic synapse](/details-term/GO:0098978)' cellular components firmly places it at the sites of synaptic communication. ## Research Directions While the primary role of [EPHA7](/details-gene/2045) in neurodevelopment is well-established, its involvement in pathology, particularly cancer, presents a compelling area for future investigation. The observation that ALL1 fusion proteins deregulate [EPHA7](/details-gene/2045) in acute leukemias ([Link](https://doi.org/10.1073/pnas.0703211104)) and that a secreted form exists in lung cancer ([Link](https://pubmed.ncbi.nlm.nih.gov/20126984/)) suggests its function can be co-opted in oncogenic processes outside the nervous system. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The subtype-specific expression of [EPHA7](/details-gene/2045) in cortical interneurons is essential for establishing their laminar position and synaptic targets. Loss of [EPHA7](/details-gene/2045) function during development would lead to disorganized cortical inhibitory circuits and an imbalance of excitation-inhibition. 2. **Hypothesis 2:** In non-neuronal contexts such as the kidney, [EPHA7](/details-gene/2045) signaling is critical for maintaining the epithelial integrity and cellular organization of the nephron. Its disruption could contribute to renal developmental abnormalities, consistent with its role in '[nephric duct morphogenesis](/details-term/GO:0072178)'. 3. **Hypothesis 3:** The aberrant expression or secretion of truncated [EPHA7](/details-gene/2045) in cancer cells disrupts normal cell-cell adhesion and Eph-ephrin signaling, promoting metastasis or activating pro-survival pathways like the ERK cascade. **Experimental Proposal for Hypothesis 1:** To test the role of [EPHA7](/details-gene/2045) in cortical interneuron circuit formation, a conditional knockout mouse model could be generated. By crossing an *Epha7*-floxed mouse with a Cre-driver line specific to interneuron progenitors (e.g., *Nkx2-1*-Cre), one could selectively delete the gene in this cell lineage. The resulting phenotype could be analyzed using a combination of techniques: immunohistochemistry to assess interneuron positioning and lamination, slice electrophysiology to measure synaptic connectivity and function, and sparse-labeling anatomical tracing to visualize detailed axonal arborization patterns. **Therapeutic Potential:** As a receptor tyrosine kinase, [EPHA7](/details-gene/2045) is a member of a highly druggable protein class. Its documented deregulation in leukemia and lung cancer makes it a potential therapeutic target. An **inhibitory** strategy would be most appropriate, aimed at blocking its aberrant pro-growth or anti-apoptotic signaling. This could be achieved through small molecule tyrosine kinase inhibitors or monoclonal antibodies that block ligand binding or receptor dimerization. The existence of a secreted form in lung cancer also raises the possibility of using therapeutic antibodies to neutralize it in the tumor microenvironment or developing it as a circulating biomarker for disease monitoring.

Genular Protein ID: 735645282

Symbol: EPHA7_HUMAN

Name: Ephrin type-A receptor 7

UniProtKB Accession Codes:

Q15375 A0AUX7 B2R8W1 B7ZLJ9 B7ZLK0 Q59G40 Q5VTU0 Q8N368 Q9H124

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 5 CPTAC 3 CTD 1 ChEBI 7 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 2 EMBL 12 Ensembl 3 EvolutionaryTrace 1 GO 30 Gene3D 6 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 20 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PIR 1 PIRSF 1 PRINTS 2 PRO 1 PROSITE 9 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 6 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 Pumba 1 RNAct 1 Reactome 3 RefSeq 4 Rhea 3 SIGNOR 1 SMART 5 SMR 1 STRING 1 SUPFAM 5 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7898931

Title: cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases.

PubMed ID: 7898931

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9267020

Title: Unified nomenclature for Eph family receptors and their ligands, the ephrins.

PubMed ID: 9267020

DOI: 10.1016/s0092-8674(00)80500-0

PubMed ID: 17726105

Title: ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias.

PubMed ID: 17726105

DOI: 10.1073/pnas.0703211104

PubMed ID: 20126984

Title: Secreted form of EphA7 in lung cancer.

PubMed ID: 20126984

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 998
  • Mass: 112097
  • Checksum: 479B9CA0D2BB06EB
  • Sequence:
    • MVFQTRYPSW IILCYIWLLR FAHTGEAQAA KEVLLLDSKA QQTELEWISS PPNGWEEISG 
LDENYTPIRT YQVCQVMEPN QNNWLRTNWI SKGNAQRIFV ELKFTLRDCN SLPGVLGTCK 
ETFNLYYYET DYDTGRNIRE NLYVKIDTIA ADESFTQGDL GERKMKLNTE VREIGPLSKK 
GFYLAFQDVG ACIALVSVKV YYKKCWSIIE NLAIFPDTVT GSEFSSLVEV RGTCVSSAEE 
EAENAPRMHC SAEGEWLVPI GKCICKAGYQ QKGDTCEPCG RGFYKSSSQD LQCSRCPTHS 
FSDKEGSSRC ECEDGYYRAP SDPPYVACTR PPSAPQNLIF NINQTTVSLE WSPPADNGGR 
NDVTYRILCK RCSWEQGECV PCGSNIGYMP QQTGLEDNYV TVMDLLAHAN YTFEVEAVNG 
VSDLSRSQRL FAAVSITTGQ AAPSQVSGVM KERVLQRSVE LSWQEPEHPN GVITEYEIKY 
YEKDQRERTY STVKTKSTSA SINNLKPGTV YVFQIRAFTA AGYGNYSPRL DVATLEEATG 
KMFEATAVSS EQNPVIIIAV VAVAGTIILV FMVFGFIIGR RHCGYSKADQ EGDEELYFHF 
KFPGTKTYID PETYEDPNRA VHQFAKELDA SCIKIERVIG AGEFGEVCSG RLKLPGKRDV 
AVAIKTLKVG YTEKQRRDFL CEASIMGQFD HPNVVHLEGV VTRGKPVMIV IEFMENGALD 
AFLRKHDGQF TVIQLVGMLR GIAAGMRYLA DMGYVHRDLA ARNILVNSNL VCKVSDFGLS 
RVIEDDPEAV YTTTGGKIPV RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM 
SNQDVIKAIE EGYRLPAPMD CPAGLHQLML DCWQKERAER PKFEQIVGIL DKMIRNPNSL 
KTPLGTCSRP ISPLLDQNTP DFTTFCSVGE WLQAIKMERY KDNFTAAGYN SLESVARMTI 
EDVMSLGITL VGHQKKIMSS IQTMRAQMLH LHGTGIQV