Details for: EFNA2

Gene ID: 1943

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: EFNA2

Ensembl ID: ENSG00000099617

Description: ephrin A2

Cell Significance Landscape

Associated with

Significant Cells

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

  • neural crest cell CL0011012
    CSI 3.58
    rCSI 2.83%
    PRS 89.32
  • intestinal epithelial cell CL0002563
    CSI 3.57
    rCSI 3.73%
    PRS 92.26
  • goblet cell CL0000160
    CSI 2.96
    rCSI 2.8%
    PRS 92.16
  • stem cell CL0000034
    CSI 2.8
    rCSI 2.7%
    PRS 91.49
  • glioblast CL0000030
    CSI 2.74
    rCSI 4.38%
    PRS 88.21
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.74
    rCSI 3.51%
    PRS 91.03
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.51
    rCSI 2.9%
    PRS 87.94
  • enterocyte CL0000584
    CSI 2.25
    rCSI 3.64%
    PRS 91.34
  • radial glial cell CL0000681
    CSI 2.15
    rCSI 2.99%
    PRS 92.74
  • peripheral nervous system neuron CL2000032
    CSI 2.03
    rCSI 2.76%
    PRS 89.2
  • BEST4+ enteroycte CL4030026
    CSI 1.71
    rCSI 2.13%
    PRS 93.48

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [EFNA2](/details-gene/1943) (ephrin A2) is a protein-coding gene located on chromosome 19p13.3 that encodes Ephrin-A2, a member of the ephrin ligand family. These proteins are ligands for the Eph family of receptor tyrosine kinases and are critical for cell-cell signaling processes. Functionally, [EFNA2](/details-gene/1943) is primarily associated with nervous system development, particularly in [axon guidance](/details-go/GO:0007411) and the regulation of cell repulsion. Expression data highlights its significant role in neural lineage cells such as the [neural crest cell](/details-cell/CL0011012) and [glioblast](/details-cell/CL0000030), as well as in the gastrointestinal tract, with high significance in [intestinal epithelial cell](/details-cell/CL0002563) populations. This dual expression pattern suggests its involvement in both neural development and epithelial tissue organization. ## Cellular Roles and Expression Landscape The expression profile of [EFNA2](/details-gene/1943) points to highly specific roles in developmental and epithelial contexts. **Overall**, the gene shows the highest significance in two distinct cellular compartments: the developing nervous system and the intestinal epithelium. In the nervous system, [EFNA2](/details-gene/1943) is a prominent marker for various progenitor and mature neural cells. It is most significant in the [neural crest cell](/details-cell/CL0011012) (CSI: 3.58), a multipotent cell population critical for vertebrate development. Its high significance is also noted in [glioblast](/details-cell/CL0000030) (CSI: 2.74), [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 2.74), [radial glial cell](/details-cell/CL0000681) (CSI: 2.15), and [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 2.03). This pattern strongly suggests a fundamental role in neurogenesis, glial cell biology, and the establishment of neural circuits. Concurrently, [EFNA2](/details-gene/1943) displays high significance in the intestinal lining. It is a key marker for the general [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 3.57) population and is also prominent in specialized cells such as the [goblet cell](/details-cell/CL0000160) (CSI: 2.96) and [enterocyte](/details-cell/CL0000584) (CSI: 2.25). This indicates a potential function in maintaining epithelial barrier integrity, cell sorting, or regulating cell migration along the crypt-villus axis. The gene's high significance in [stem cell](/details-cell/CL0000034) (CSI: 2.80) further supports its involvement in processes of differentiation and tissue renewal in both neural and epithelial contexts. ## Pathways and Molecular Function Functionally, [EFNA2](/details-gene/1943) acts as a ligand that binds to Eph receptors, initiating downstream signaling cascades. Its molecular function is primarily defined by [Ephrin receptor binding](/details-go/GO:0046875). As a cell-surface protein anchored to the [plasma membrane](/details-go/GO:0005886), it facilitates direct [cell-cell signaling](/details-go/GO:0007267). The gene's biological roles are well-documented in the context of developmental biology, as highlighted by its association with Reactome pathways like [Developmental biology](/details-reactome/R-HSA-1266738) and [Nervous system development](/details-reactome/R-HSA-9675108). Its high expression in neural cells is consistent with its deep involvement in [Axon guidance](/details-reactome/R-HSA-422475), a process governed by repulsive cues that steer growing axons to their correct targets. This is further specified by pathways such as [Eph-ephrin mediated repulsion of cells](/details-reactome/R-HSA-3928665) and [Epha-mediated growth cone collapse](/details-reactome/R-HSA-3928663). While its role in the intestine is less defined by these pathways, its function in cell-cell signaling is likely repurposed to manage the complex cellular organization of the gut epithelium. Initial characterization and mapping of the gene have been previously described ([Link](https://doi.org/10.1006/geno.1997.5088), [Link](https://doi.org/10.1006/bbrc.1998.9618)). ## Research Directions The specific and high-level expression of [EFNA2](/details-gene/1943) in distinct cell populations, particularly in both development and cancer-related cell types like [glioblast](/details-cell/CL0000030), opens several avenues for future research. Based on the available data, the following hypotheses can be proposed: 1. In the intestinal epithelium, [EFNA2](/details-gene/1943) mediates cell sorting and positioning along the crypt-villus axis. Its function in cell repulsion may prevent the intermingling of different epithelial cell types (e.g., [goblet cell](/details-cell/CL0000160), [enterocyte](/details-cell/CL0000584)) and guide their orderly migration from the stem cell niche at the crypt base. 2. In glioblastoma, the high expression of [EFNA2](/details-gene/1943) on [glioblast](/details-cell/CL0000030) cells may contribute to tumor progression by promoting cell-cell repulsion between tumor cells, thereby facilitating their dispersal and invasion into surrounding brain tissue. To test the second hypothesis, a key experiment would be to use CRISPR-Cas9 to knock out [EFNA2](/details-gene/1943) in a human glioblastoma cell line. The invasive potential of these knockout cells could then be compared to wild-type control cells using a 3D organoid or spheroid invasion assay, where tumor spheroids are embedded in an extracellular matrix. A reduction in the distance and number of cells invading the matrix from the [EFNA2](/details-gene/1943)-knockout spheroids would support its role as a driver of glioblastoma invasion. Given its localization on the cell surface and its potential role in promoting glioblastoma invasion, [EFNA2](/details-gene/1943) may represent a viable therapeutic target. A strategy involving inhibition would be most appropriate. This could be pursued through the development of monoclonal antibodies that block the interaction of Ephrin-A2 with its Eph receptors or through soluble Eph receptor decoys that sequester Ephrin-A2, thereby neutralizing its pro-invasive signaling.

Genular Protein ID: 1855656246

Symbol: EFNA2_HUMAN

Name: Ephrin-A2

UniProtKB Accession Codes:

O43921 O76020

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 EvolutionaryTrace 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9465306

Title: Characterization of the genes for mouse LERK-3/Ephrin-A3 (Epl3), mouse LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6): conservation of intron/exon structure.

PubMed ID: 9465306

DOI: 10.1006/geno.1997.5088

PubMed ID: 9826538

Title: Cloning, chromosomal mapping, and tissue expression of the gene encoding the human Eph-family kinase ligand ephrin-A2.

PubMed ID: 9826538

DOI: 10.1006/bbrc.1998.9618

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 19836338

Title: Structural plasticity of EPH receptor A4 facilitates cross-class ephrin signaling.

PubMed ID: 19836338

DOI: 10.1016/j.str.2009.07.018

Sequence Information:

  • Length: 213
  • Mass: 23878
  • Checksum: 33C9FB1A8168B2D0
  • Sequence:
    • MAPAQRPLLP LLLLLLPLPP PPFARAEDAA RANSDRYAVY WNRSNPRFHA GAGDDGGGYT 
VEVSINDYLD IYCPHYGAPL PPAERMEHYV LYMVNGEGHA SCDHRQRGFK RWECNRPAAP 
GGPLKFSEKF QLFTPFSLGF EFRPGHEYYY ISATPPNAVD RPCLRLKVYV RPTNETLYEA 
PEPIFTSNNS CSSPGGCRLF LSTIPVLWTL LGS