Details for: ROBO3

Gene ID: 64221

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: ROBO3

Ensembl ID: ENSG00000154134

Description: roundabout guidance receptor 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • blood vessel endothelial cell CL0000071
    CSI 7.56
    rCSI 15.69%
    PRS 98.58
  • interneuron CL0000099
    CSI 6.63
    rCSI 13.32%
    PRS 97.71
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 5.75
    rCSI 7.38%
    PRS 98.08
  • Mueller cell CL0000636
    CSI 5.52
    rCSI 12.61%
    PRS 97.28
  • neural progenitor cell CL0011020
    CSI 4.92
    rCSI 21.66%
    PRS 94.57
  • midbrain dopaminergic neuron CL2000097
    CSI 4.65
    rCSI 29.77%
    PRS 96.21
  • Bergmann glial cell CL0000644
    CSI 4.26
    rCSI 5.83%
    PRS 96.75
  • hematopoietic stem cell CL0000037
    CSI 3.89
    rCSI 2.58%
    PRS 99.27
  • adventitial cell CL0002503
    CSI 2.94
    rCSI 7.02%
    PRS 99.43
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.76
    rCSI 10.43%
    PRS 95.85
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.7
    rCSI 2.44%
    PRS 99.02
  • glioblast CL0000030
    CSI 2.63
    rCSI 4.19%
    PRS 96.99
  • glial cell CL0000125
    CSI 2.34
    rCSI 8.93%
    PRS 96.73
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.31
    rCSI 5.17%
    PRS 96.4
  • cardiac neuron CL0010022
    CSI 1.52
    rCSI 4.87%
    PRS 98.59

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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  • 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 [ROBO3](/details-gene/64221) (Roundabout Guidance Receptor 3) is a protein-coding gene located on chromosome 11q24.2. It encodes a member of the ROBO family of transmembrane receptors, which are critical for developmental processes, particularly axon guidance. Functional annotations strongly link [ROBO3](/details-gene/64221) to the regulation of neuronal migration and pathway finding, cell-cell adhesion, and chemotaxis. **Overall**, expression data highlights its significant role not only in diverse neuronal and glial cell populations of the central nervous system but also in the vascular endothelium and hematopoietic progenitor cells, suggesting a broader function in cellular guidance and organization across multiple tissues. ## Cellular Roles and Expression Landscape The expression profile of [ROBO3](/details-gene/64221) underscores its primary function in the development and maintenance of the nervous and vascular systems. **Overall**, it shows the highest significance in [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 7.56), indicating a key role in the vasculature. This is complemented by strong significance in a wide array of neural cell types, establishing it as a crucial component of the central nervous system. Functionally, these cell types can be grouped: * **Neuronal and Progenitor Cells:** [ROBO3](/details-gene/64221) is highly significant in various neuronal populations, including [interneuron](/details-cell/CL0000099) (CSI: 6.63), [midbrain dopaminergic neuron](/details-cell/CL2000097) (CSI: 4.65), and [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) (CSI: 2.76). Its high scores in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 5.75) and [neural progenitor cell](/details-cell/CL0011020) (CSI: 4.92) are consistent with a fundamental role during neurogenesis. * **Glial and Support Cells:** The gene is also a significant marker in several glial cell types that support neuronal function, such as [Mueller cell](/details-cell/CL0000636) (CSI: 5.52), [Bergmann glial cell](/details-cell/CL0000644) (CSI: 4.26), and [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 2.31). Its expression in [glioblast](/details-cell/CL0000030) (CSI: 2.63) may suggest a role in brain tumorigenesis. * **Hematopoietic System:** Interestingly, [ROBO3](/details-gene/64221) shows notable significance in [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 3.89) and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.70), suggesting a potential function in hematopoietic development or cell trafficking. This expression pattern suggests that [ROBO3](/details-gene/64221) is a key guidance receptor mediating cellular positioning and interaction, primarily in neurovascular contexts. ## Pathways and Molecular Function The functions of [ROBO3](/details-gene/64221) are predominantly related to cell guidance and nervous system development, as detailed by its functional annotations. Its involvement in the Gene Ontology biological process of '[Axon guidance](/details-go/GO:0007411)' ([GO:0007411](https://www.ebi.ac.uk/QuickGO/term/GO:0007411)) is a central theme, further specified by its role in '[Axon midline choice point recognition](/details-go/GO:0016199)' ([GO:0016199](https://www.ebi.ac.uk/QuickGO/term/GO:0016199)). This is strongly supported by its association with Reactome pathways such as '[Axon guidance](/details-reactome/R-HSA-422475)' ([R-HSA-422475](https://reactome.org/content/detail/R-HSA-422475)) and '[Regulation of commissural axon pathfinding by slit and robo](/details-reactome/R-HSA-428542)' ([R-HSA-428542](https://reactome.org/content/detail/R-HSA-428542)). Indeed, mutations in [ROBO3](/details-gene/64221) have been shown to disrupt axon pathway crossing in the human hindbrain ([Link](https://doi.org/10.1126/science.1096437)). At the molecular level, [ROBO3](/details-gene/64221) functions in '[Homophilic cell adhesion via plasma membrane adhesion molecules](/details-go/GO:0007156)' ([GO:0007156](https://www.ebi.ac.uk/QuickGO/term/GO:0007156)) and '[Chemotaxis](/details-go/GO:0006935)' ([GO:0006935](https://www.ebi.ac.uk/QuickGO/term/GO:0006935)), processes that are critical for organizing complex tissues. Its localization to the '[Plasma membrane](/details-go/GO:0005886)' ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) and '[Axon](/details-go/GO:0030424)' ([GO:0030424](https://www.ebi.ac.uk/QuickGO/term/GO:0030424)) is consistent with its function as a transmembrane receptor that senses extracellular cues, as demonstrated by its binding to NELL2 ([Link](https://doi.org/10.1038/s41467-020-15211-1)). ## Research Directions The established role of [ROBO3](/details-gene/64221) in axon guidance, combined with its high expression in non-neuronal cells, opens several avenues for future research. The parallel between neural pathfinding and other biological processes like angiogenesis and immune cell trafficking suggests conserved functions for ROBO signaling. **Testable Hypotheses:** 1. Given its high significance in [blood vessel endothelial cell](/details-cell/CL0000071), [ROBO3](/details-gene/64221) may play a critical role in vascular guidance and angiogenesis by responding to Slit or other ligands, mirroring its function in axon pathfinding. 2. The notable expression of [ROBO3](/details-gene/64221) in [hematopoietic stem cell](/details-cell/CL0000037) suggests it may mediate the migration and homing of these progenitors to specific niches within the bone marrow, potentially contributing to the regulation of hematopoiesis. 3. In the context of cancer, [ROBO3](/details-gene/64221) expression in [glioblast](/details-cell/CL0000030) may promote tumor cell invasion and neo-angiogenesis, making it a contributor to glioma pathology. **Proposed Experiment:** To test the hypothesis that [ROBO3](/details-gene/64221) is involved in angiogenesis, one could perform a functional study using human umbilical vein endothelial cells (HUVECs). [ROBO3](/details-gene/64221) expression would first be silenced using CRISPR-Cas9 or siRNA. The functional consequences would then be assessed using an in-vitro tube formation assay, where control and [ROBO3](/details-gene/64221)-deficient HUVECs are plated on a basement membrane matrix and their ability to form capillary-like networks is quantified. A significant reduction in network formation in the knockdown cells would support a pro-angiogenic role for [ROBO3](/details-gene/64221). **Therapeutic Potential:** As a cell surface receptor, [ROBO3](/details-gene/64221) is an accessible drug target. Its expression in [glioblast](/details-cell/CL0000030) and its potential role in promoting angiogenesis suggest it could be a target for cancer therapy. An **inhibitory** strategy using monoclonal antibodies or small molecule antagonists could disrupt tumor vascularization and cell migration, potentially slowing tumor growth and invasion. Such a therapeutic would leverage the foundational role of [ROBO3](/details-gene/64221) in mediating cellular guidance.

Genular Protein ID: 2778131097

Symbol: ROBO3_HUMAN

Name: Roundabout homolog 3

UniProtKB Accession Codes:

Q96MS0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 ExpressionAtlas 1 GO 10 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 8 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15105459

Title: Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.

PubMed ID: 15105459

DOI: 10.1126/science.1096437

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 32198364

Title: NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance.

PubMed ID: 32198364

DOI: 10.1038/s41467-020-15211-1

Sequence Information:

  • Length: 1386
  • Mass: 148209
  • Checksum: 955A7300A2BDA27F
  • Sequence:
    • MLRYLLKTLL QMNLFADSLA GDISNSSELL LGFNSSLAAL NHTLLPPGDP SLNGSRVGPE 
DAMPRIVEQP PDLLVSRGEP ATLPCRAEGR PRPNIEWYKN GARVATVRED PRAHRLLLPS 
GALFFPRIVH GRRARPDEGV YTCVARNYLG AAASRNASLE VAVLRDDFRQ SPGNVVVAVG 
EPAVLECVPP RGHPEPSVSW RKDGARLKEE EGRITIRGGK LMMSHTLKSD AGMYVCVASN 
MAGERESAAA EVMVLERPSF LRRPVNQVVL ADAPVTFLCE VKGDPPPRLR WRKEDGELPT 
GRYEIRSDHS LWIGHVSAED EGTYTCVAEN SVGRAEASGS LSVHVPPQLV TQPQDQMAAP 
GESVAFQCET KGNPPPAIFW QKEGSQVLLF PSQSLQPTGR FSVSPRGQLN ITAVQRGDAG 
YYVCQAVSVA GSILAKALLE IKGASLDGLP PVILQGPANQ TLVLGSSVWL PCRVTGNPQP 
SVRWKKDGQW LQGDDLQFKT MANGTLYIAN VQEMDMGFYS CVAKSSTGEA TWSGWLKMRE 
DWGVSPDPPT EPSSPPGAPS QPVVTEITKN SITLTWKPNP QTGAAVTSYV IEAFSPAAGN 
TWRTVADGVQ LETHTVSGLQ PNTIYLFLVR AVGAWGLSEP SPVSEPVRTQ DSSPSRPVED 
PWRGQQGLAE VAVRLQEPIV LGPRTLQVSW TVDGPVQLVQ GFRVSWRVAG PEGGSWTMLD 
LQSPSQQSTV LRGLPPGTQI QIKVQAQGQE GLGAESLSVT RSIPEEAPSG PPQGVAVALG 
GDGNSSITVS WEPPLPSQQN GVITEYQIWC LGNESRFHLN RSAAGWARSA MLRGLVPGLL 
YRTLVAAATS AGVGVPSAPV LVQLPSPPDL EPGLEVGAGL AVRLARVLRE PAFLAGSGAA 
CGALLLGLCA ALYWRRKQRK ELSHYTASFA YTPAVSFPHS EGLSGASSRP PMGLGPAPYS 
WLADSWPHPS RSPSAQEPRG SCCPSNPDPD DRYYNEAGIS LYLAQTARGT AAPGEGPVYS 
TIDPAGEELQ TFHGGFPQHP SGDLGPWSQY APPEWSQGDS GAKGGKVKLL GKPVQMPSLN 
WPEALPPPPP SCELSCLEGP EEELEGSSEP EEWCPPMPER SHLTEPSSSG GCLVTPSRRE 
TPSPTPSYGQ QSTATLTPSP PDPPQPPTDM PHLHQMPRRV PLGPSSPLSV SQPMLGIREA 
RPAGLGAGPA ASPHLSPSPA PSTASSAPGR TWQGNGEMTP PLQGPRARFR KKPKALPYRR 
ENSPGDLPPP PLPPPEEEAS WALELRAAGS MSSLERERSG ERKAVQAVPL AAQRVLHPDE 
EAWLPYSRPS FLSRGQGTST CSTAGSNSSR GSSSSRGSRG PGRSRSRSQS RSQSQRPGQK 
RREEPR