Details for: EPHB6

Gene ID: 2051

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: EPHB6

Ensembl ID: ENSG00000106123

Description: EPH receptor B6

Cell Significance Landscape

Associated with

Significant Cells

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

  • keratinocyte CL0000312
    CSI 14.12
    rCSI 11.84%
    PRS 86.91
  • common myeloid progenitor CL0000049
    CSI 8.38
    rCSI 6.78%
    PRS 87.05
  • myoepithelial cell CL0000185
    CSI 5.34
    rCSI 13.52%
    PRS 88.69
  • myofibroblast cell CL0000186
    CSI 5.19
    rCSI 7.19%
    PRS 81.35
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 4.83
    rCSI 17.38%
    PRS 66.7
  • sst GABAergic cortical interneuron CL4023017
    CSI 4.59
    rCSI 5.92%
    PRS 69.95
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 4.46
    rCSI 4.55%
    PRS 92.29
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.76
    rCSI 3.62%
    PRS 84.18
  • vascular associated smooth muscle cell CL0000359
    CSI 3.41
    rCSI 11.06%
    PRS 82.98
  • early lymphoid progenitor CL0000936
    CSI 3.39
    rCSI 2.98%
    PRS 89.11
  • CD4-positive helper T cell CL0000492
    CSI 3.12
    rCSI 2.36%
    PRS 94.55
  • inhibitory interneuron CL0000498
    CSI 3.04
    rCSI 7.01%
    PRS 73.96
  • cerebellar granule cell CL0001031
    CSI 2.93
    rCSI 4.3%
    PRS 78.44
  • Mueller cell CL0000636
    CSI 2.78
    rCSI 6.35%
    PRS 77.12
  • intrahepatic cholangiocyte CL0002538
    CSI 2.77
    rCSI 6.66%
    PRS 87.29
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.72
    rCSI 2.67%
    PRS 95.07
  • cerebral cortex neuron CL0010012
    CSI 2.43
    rCSI 9.91%
    PRS 76.94
  • vascular leptomeningeal cell CL4023051
    CSI 2.32
    rCSI 4.07%
    PRS 79.66
  • common lymphoid progenitor CL0000051
    CSI 2.22
    rCSI 2.96%
    PRS 95.81
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.18
    rCSI 3.51%
    PRS 70.12
  • basal cell of epidermis CL0002187
    CSI 2.15
    rCSI 3.81%
    PRS 54.36
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.1
    rCSI 3.53%
    PRS 68.71
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.98
    rCSI 4.81%
    PRS 66.59
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.95
    rCSI 2.42%
    PRS 66.68
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.84
    rCSI 4%
    PRS 72.96
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.84
    rCSI 10.81%
    PRS 69.24
  • direct pathway medium spiny neuron CL4023026
    CSI 1.82
    rCSI 43.67%
    PRS 66.62
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.82
    rCSI 43.86%
    PRS 67.09
  • hair follicular keratinocyte CL2000092
    CSI 1.75
    rCSI 30.42%
    PRS 91.28
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.73
    rCSI 5.41%
    PRS 70.24
  • respiratory basal cell CL0002633
    CSI 1.71
    rCSI 1.77%
    PRS 87.94
  • glutamatergic neuron CL0000679
    CSI 1.56
    rCSI 3.21%
    PRS 72.25
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.48
    rCSI 3.55%
    PRS 72.6
  • pancreatic ductal cell CL0002079
    CSI 1.47
    rCSI 2.86%
    PRS 87.61
  • serotonergic neuron CL0000850
    CSI 1.26
    rCSI 5.64%
    PRS 69.34
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.21
    rCSI 3.98%
    PRS 71.45
  • GABAergic neuron CL0000617
    CSI 1.21
    rCSI 4.05%
    PRS 69.62
  • luminal cell of prostate epithelium CL0002340
    CSI 1.13
    rCSI 6.09%
    PRS 90.91
  • dopaminergic neuron CL0000700
    CSI 1.05
    rCSI 5.94%
    PRS 72.01
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.03
    rCSI 3.9%
    PRS 69.08
  • GABAergic amacrine cell CL4030027
    CSI 0.95
    rCSI 3.24%
    PRS 71.24
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.94
    rCSI 2.73%
    PRS 84.03
  • central nervous system neuron CL2000029
    CSI 0.46
    rCSI 3.39%
    PRS 73.78
  • medium spiny neuron CL1001474
    CSI 0.17
    rCSI 1.48%
    PRS 74.23

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)

Loading network (please wait)...

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 [EPHB6](/details-gene/2051) (Ephrin type-B receptor 6) is a protein-coding gene located on chromosome 7q34 that encodes a member of the Eph receptor family of receptor tyrosine kinases. Uniquely, [EPHB6](/details-gene/2051) is considered a kinase-defective receptor, suggesting it functions primarily as a modulator or scaffold protein in signaling complexes. **Overall**, its expression is most significant in [keratinocytes](/details-cell/CL0000312), hematopoietic progenitors like the [common myeloid progenitor](/details-cell/CL0000049), and various neuronal subtypes. Its involvement in fundamental processes such as [axon guidance](/details-term/GO0007411) and the [Ephrin receptor signaling pathway](/details-term/GO0048013) highlights its diverse roles in tissue development, cell-cell communication, and cellular migration across epithelial, immune, and nervous systems. ## Cellular Roles and Expression Landscape The expression profile of [EPHB6](/details-gene/2051) suggests a broad but distinct functional significance across multiple tissues. **Overall**, its most prominent role appears to be in epithelial tissues, where it is a top marker for [keratinocytes](/details-cell/CL0000312) (CSI: 14.12). Its significance is also high in other epithelial and structural cells, including [myoepithelial cells](/details-cell/CL0000185), [myofibroblast cells](/details-cell/CL0000186), and [fallopian tube secretory epithelial cells](/details-cell/CL4030006). This pattern is consistent with the established role of Eph/ephrin signaling in mediating cell adhesion and repulsion, which is critical for maintaining tissue architecture and boundaries. [EPHB6](/details-gene/2051) is also a significant marker in the hematopoietic and immune systems. High significance is observed in progenitor populations, such as the [common myeloid progenitor](/details-cell/CL0000049) and [early lymphoid progenitor](/details-cell/CL0000936), as well as in developing T cells like the [double-positive, alpha-beta thymocyte](/details-cell/CL0000809) and mature [CD4-positive helper T cells](/details-cell/CL0000492). This expression profile is supported by research indicating its role in modulating T-cell receptor signaling ([Link](https://doi.org/10.1074/jbc.m208179200)). Furthermore, consistent with its functional annotations, [EPHB6](/details-gene/2051) is significantly expressed in the nervous system. It serves as a marker for diverse neuronal populations, including [L5 extratelencephalic projecting glutamatergic cortical neurons](/details-cell/CL4023041), [sst GABAergic cortical interneurons](/details-cell/CL4023017), and [cerebellar granule cells](/details-cell/CL0001031). This expression pattern underscores its canonical role in nervous system development and axon guidance. ## Pathways and Molecular Function Functionally, [EPHB6](/details-gene/2051) is deeply integrated into cell-cell signaling networks. Its primary annotations point to involvement in the [Ephrin receptor signaling pathway](/details-term/GO0048013) and [axon guidance](/details-term/GO0007411), processes governed by the interaction between Eph receptors and their ephrin ligands on adjacent cells. These interactions are detailed in Reactome pathways such as [Eph-ephrin signaling](/details-pathway/R-HSA-2682334) and [Eph-ephrin mediated repulsion of cells](/details-pathway/R-HSA-3928665). As a member of the transmembrane receptor family, [EPHB6](/details-gene/2051) is localized to the [plasma membrane](/details-term/GO0005886), where it exerts its function. A critical feature of [EPHB6](/details-gene/2051) is its lack of intrinsic kinase activity. Instead of directly phosphorylating substrates, it is thought to function by forming heterodimers with other kinase-active EphB receptors, such as EphB1, leading to its transphosphorylation and the subsequent modulation of downstream signaling pathways ([Link](https://doi.org/10.1074/jbc.m108011200)). This scaffolding or modulatory role allows it to influence a wide range of cellular behaviors, including cell adhesion and migration, in a biphasic manner ([Link](https://doi.org/10.1074/jbc.m500010200)). ## Research Directions The diverse expression pattern and unique signaling mechanism of [EPHB6](/details-gene/2051) present several avenues for future research, particularly regarding its role in tissue homeostasis and disease. **Proposed Testable Hypotheses:** 1. Given its exceptionally high significance in [keratinocytes](/details-cell/CL0000312), [EPHB6](/details-gene/2051) likely functions as a key regulator of epidermal stratification and barrier integrity by modulating intercellular adhesion and differentiation programs. 2. Based on its expression in thymocytes and T-cells and its documented inhibition of JNK signaling ([Link](https://doi.org/10.1074/jbc.m208179200)), [EPHB6](/details-gene/2051) may act as a rheostat for T-cell activation, setting the signaling threshold required for a productive immune response and preventing autoimmunity. 3. The context-dependent role of [EPHB6](/details-gene/2051) in cancer ([Link](https://doi.org/10.1038/onc.2009.18), [Link](https://pubmed.ncbi.nlm.nih.gov/18425388/)) suggests that its expression level could serve as a biomarker to predict tumor invasiveness, with loss of function promoting metastasis in some contexts (e.g., breast cancer) while its expression provides neoantigens in others (e.g., glioma). **Key Experimental Approach:** To test the hypothesis that [EPHB6](/details-gene/2051) is critical for epidermal barrier function, a conditional knockout mouse model could be generated using a Krt14-Cre driver to specifically delete *Ephb6* in basal keratinocytes. The resulting mice would be analyzed for skin abnormalities using histology to assess epidermal thickness and cellular organization. Barrier function could be quantitatively measured via transepidermal water loss (TEWL) assays. Furthermore, immunofluorescence staining for key adhesion molecules (e.g., E-cadherin, desmogleins) and differentiation markers (e.g., loricrin, filaggrin) in the knockout skin would reveal the specific molecular pathways disrupted by the loss of [EPHB6](/details-gene/2051). **Therapeutic Potential:** The therapeutic potential of targeting [EPHB6](/details-gene/2051) is highly context-dependent. In cancers where its expression is associated with a less aggressive phenotype, such as breast cancer ([Link](https://doi.org/10.1038/onc.2009.18)), strategies aimed at **activation** or restoration of its signaling function could be beneficial. This might involve developing small molecules that stabilize its interaction with other Eph receptors. Conversely, in malignancies like glioma, where [EPHB6](/details-gene/2051)-derived peptides are recognized by cytotoxic T-lymphocytes ([Link](https://doi.org/10.1111/j.1349-7006.2008.00866.x)), it represents a promising target for **inhibition** or elimination via immunotherapy, such as cancer vaccines or engineered T-cell therapies.

Genular Protein ID: 538486877

Symbol: EPHB6_HUMAN

Name: Ephrin type-B receptor 6

UniProtKB Accession Codes:

O15197 A4D2I7 A8CDT5 D3DXD3 Q2TB23 Q2TB24

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CDD 3 CPTAC 1 CTD 1 ChEBI 1 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EMBL 13 GO 10 Gene3D 6 GeneCards 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 InParanoid 1 IntAct 1 InterPro 16 KEGG 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PIRSF 1 PRINTS 2 PRO 1 PROSITE 6 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 6 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 4 RefSeq 2 SIGNOR 1 SMART 4 SMR 1 STRING 1 SUPFAM 5 SignaLink 1 TreeFam 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9207182

Title: Expression of a kinase-defective Eph-like receptor in the normal human brain.

PubMed ID: 9207182

DOI: 10.1006/bbrc.1997.6812

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

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: 18425388

Title: Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24+ malignant glioma patients.

PubMed ID: 18425388

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 11713248

Title: The kinase-null EphB6 receptor undergoes transphosphorylation in a complex with EphB1.

PubMed ID: 11713248

DOI: 10.1074/jbc.m108011200

PubMed ID: 12517763

Title: The EphB6 receptor inhibits JNK activation in T lymphocytes and modulates T cell receptor-mediated responses.

PubMed ID: 12517763

DOI: 10.1074/jbc.m208179200

PubMed ID: 15955811

Title: Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration.

PubMed ID: 15955811

DOI: 10.1074/jbc.m500010200

PubMed ID: 18754880

Title: Erythropoietin-producing hepatocyte B6 variant-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in human leukocyte antigen-A2+ glioma patients.

PubMed ID: 18754880

DOI: 10.1111/j.1349-7006.2008.00866.x

PubMed ID: 19234485

Title: EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells.

PubMed ID: 19234485

DOI: 10.1038/onc.2009.18

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: 1021
  • Mass: 110700
  • Checksum: BF1D4D9BE34358A5
  • Sequence:
    • MATEGAAQLG NRVAGMVCSL WVLLLVSSVL ALEEVLLDTT GETSEIGWLT YPPGGWDEVS 
VLDDQRRLTR TFEACHVAGA PPGTGQDNWL QTHFVERRGA QRAHIRLHFS VRACSSLGVS 
GGTCRETFTL YYRQAEEPDS PDSVSSWHLK RWTKVDTIAA DESFPSSSSS SSSSSSAAWA 
VGPHGAGQRA GLQLNVKERS FGPLTQRGFY VAFQDTGACL ALVAVRLFSY TCPAVLRSFA 
SFPETQASGA GGASLVAAVG TCVAHAEPEE DGVGGQAGGS PPRLHCNGEG KWMVAVGGCR 
CQPGYQPARG DKACQACPRG LYKSSAGNAP CSPCPARSHA PNPAAPVCPC LEGFYRASSD 
PPEAPCTGPP SAPQELWFEV QGSALMLHWR LPRELGGRGD LLFNVVCKEC EGRQEPASGG 
GGTCHRCRDE VHFDPRQRGL TESRVLVGGL RAHVPYILEV QAVNGVSELS PDPPQAAAIN 
VSTSHEVPSA VPVVHQVSRA SNSITVSWPQ PDQTNGNILD YQLRYYDQAE DESHSFTLTS 
ETNTATVTQL SPGHIYGFQV RARTAAGHGP YGGKVYFQTL PQGELSSQLP ERLSLVIGSI 
LGALAFLLLA AITVLAVVFQ RKRRGTGYTE QLQQYSSPGL GVKYYIDPST YEDPCQAIRE 
LAREVDPAYI KIEEVIGTGS FGEVRQGRLQ PRGRREQTVA IQALWAGGAE SLQMTFLGRA 
AVLGQFQHPN ILRLEGVVTK SRPLMVLTEF MELGPLDSFL RQREGQFSSL QLVAMQRGVA 
AAMQYLSSFA FVHRSLSAHS VLVNSHLVCK VARLGHSPQG PSCLLRWAAP EVIAHGKHTT 
SSDVWSFGIL MWEVMSYGER PYWDMSEQEV LNAIEQEFRL PPPPGCPPGL HLLMLDTWQK 
DRARRPHFDQ LVAAFDKMIR KPDTLQAGGD PGERPSQALL TPVALDFPCL DSPQAWLSAI 
GLECYQDNFS KFGLCTFSDV AQLSLEDLPA LGITLAGHQK KLLHHIQLLQ QHLRQQGSVE 
V

Genular Protein ID: 681707333

Symbol: F8WCM8_HUMAN

Name: N/A

UniProtKB Accession Codes:

F8WCM8

Database IDs:

ARBA 8 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 3 CTD 1 ChEBI 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 4 GO 7 Gene3D 6 GeneTree 1 HGNC 1 InterPro 16 KEGG 1 MANE-Select 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PIRSF 1 PIRSR 2 PRINTS 2 PROSITE 10 PeptideAtlas 1 Pfam 6 Proteomes 2 ProteomicsDB 2 RefSeq 4 SAM 3 SMART 4 SUPFAM 5 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 1022
  • Mass: 110771
  • Checksum: 5038EA11DEE6FFCE
  • Sequence:
    • MATEGAAQLG NRVAGMVCSL WVLLLVSSVL ALEEVLLDTT GETSEIGWLT YPPGGWDEVS 
VLDDQRRLTR TFEACHVAGA PPGTGQDNWL QTHFVERRGA QRAHIRLHFS VRACSSLGVS 
GGTCRETFTL YYRQAEEPDS PDSVSSWHLK RWTKVDTIAA DESFPSSSSS SSSSSSSAAW 
AVGPHGAGQR AGLQLNVKER SFGPLTQRGF YVAFQDTGAC LALVAVRLFS YTCPAVLRSF 
ASFPETQASG AGGASLVAAV GTCVAHAEPE EDGVGGQAGG SPPRLHCNGE GKWMVAVGGC 
RCQPGYQPAR GDKACQACPR GLYKASAGNA PCSPCPARSH APNPAAPVCP CLEGFYRASS 
DPPEAPCTGP PSAPQELWFE VQGSALMLHW RLPRELGGRG DLLFNVVCKE CEGRQEPASG 
GGGTCHRCRD EVHFDPRQRG LTESRVLVGG LRAHVPYILE VQAVNGVSEL SPDPPQAAAI 
NVSTSHEVPS AVPVVHQVSR ASNSITVSWP QPDQTNGNIL DYQLRYYDQA EDESHSFTLT 
SETNTATVTQ LSPGHIYGFQ VRARTAAGHG PYGGKVYFQT LPQGELSSQL PERLSLVIGS 
ILGALAFLLL AAITVLAVVF QRKRRGTGYT EQLQQYSSPG LGVKYYIDPS TYEDPCQAIR 
ELAREVDPAY IKIEEVIGTG SFGEVRQGRL QPRGRREQTV AIQALWAGGA ESLQMTFLGR 
AAVLGQFQHP NILRLEGVVT KSRPLMVLTE FMELGPLDSF LRQREGQFSS LQLVAMQRGV 
AAAMQYLSSF AFVHRSLSAH SVLVNSHLVC KVARLGHSPQ GPSCLLRWAA PEVIAHGKHT 
TSSDVWSFGI LMWEVMSYGE RPYWDMSEQE VLNAIEQEFR LPPPPGCPPG LHLLMLDTWQ 
KDRARRPHFD QLVAAFDKMI RKPDTLQAGG DPGERPSQAL LTPVALDFPC LDSPQAWLSA 
IGLECYQDNF SKFGLCTFSD VAQLSLEDLP ALGITLAGHQ KKLLHHIQLL QQHLRQQGSV 
EV