Details for: RGMA

Gene ID: 56963

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: RGMA

Ensembl ID: ENSG00000182175

Description: repulsive guidance molecule BMP co-receptor a

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • macroglial cell CL0000126
    CSI 7.47
    rCSI 19.2%
    PRS 89.73
  • Bergmann glial cell CL0000644
    CSI 6.29
    rCSI 8.61%
    PRS 86.86
  • mature astrocyte CL0002627
    CSI 3.88
    rCSI 16.5%
    PRS 87.31
  • glioblast CL0000030
    CSI 3.72
    rCSI 5.94%
    PRS 86.64
  • enteric smooth muscle cell CL0002504
    CSI 3.67
    rCSI 5.23%
    PRS 92.92
  • interneuron CL0000099
    CSI 3.51
    rCSI 7.05%
    PRS 88.13
  • radial glial cell CL0000681
    CSI 3.44
    rCSI 4.78%
    PRS 91.52
  • fibroblast of breast CL4006000
    CSI 3.44
    rCSI 14.45%
    PRS 94.57
  • mesodermal cell CL0000222
    CSI 3.09
    rCSI 3.7%
    PRS 92.08
  • neural crest cell CL0011012
    CSI 3.01
    rCSI 2.38%
    PRS 87.42
  • skeletal muscle satellite cell CL0000594
    CSI 2.92
    rCSI 8.52%
    PRS 96.79
  • myofibroblast cell CL0000186
    CSI 2.84
    rCSI 3.93%
    PRS 90.33
  • vascular associated smooth muscle cell CL0000359
    CSI 2.69
    rCSI 8.74%
    PRS 91.51
  • vascular leptomeningeal cell CL4023051
    CSI 2.47
    rCSI 4.33%
    PRS 90.42
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.43
    rCSI 3.11%
    PRS 89.85
  • ependymal cell CL0000065
    CSI 2.42
    rCSI 4.91%
    PRS 77.79
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.33
    rCSI 7.29%
    PRS 83.61
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.3
    rCSI 2.66%
    PRS 86.45
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.06
    rCSI 4.63%
    PRS 82.77
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.05
    rCSI 3.62%
    PRS 81.89
  • alveolar adventitial fibroblast CL4028006
    CSI 1.93
    rCSI 3.05%
    PRS 93.98
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.9
    rCSI 5.62%
    PRS 92.68
  • peripheral nervous system neuron CL2000032
    CSI 1.75
    rCSI 2.39%
    PRS 87.43
  • neural cell CL0002319
    CSI 1.75
    rCSI 6.62%
    PRS 80.79
  • mesenchymal cell CL0008019
    CSI 1.75
    rCSI 4.45%
    PRS 88.87
  • fibroblast of cardiac tissue CL0002548
    CSI 1.62
    rCSI 7.74%
    PRS 93.89
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.21
    rCSI 2.94%
    PRS 80.42
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.17
    rCSI 3.83%
    PRS 83.39
  • forebrain radial glial cell CL0013000
    CSI 1.15
    rCSI 3.7%
    PRS 92.77
  • pancreatic ductal cell CL0002079
    CSI 1.07
    rCSI 2.08%
    PRS 94.06
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.02
    rCSI 3.67%
    PRS 80.68
  • midbrain dopaminergic neuron CL2000097
    CSI 1.02
    rCSI 6.51%
    PRS 87.65
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.93
    rCSI 2.68%
    PRS 92.29
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.53
    rCSI 3.12%
    PRS 82.89
  • mesenchymal stem cell CL0000134
    CSI 0.23
    rCSI 2.5%
    PRS 94.24

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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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 [RGMA](/details-gene/56963) (Repulsive Guidance Molecule BMP Co-receptor A) is a protein-coding gene located on chromosome 15q26.1. It functions as a GPI-anchored cell surface protein that acts as a co-receptor for Bone Morphogenetic Proteins (BMPs) and is a critical component of repulsive axon guidance signaling. Its expression is most significant in the central nervous system, particularly within glial lineages such as [macroglial cells](/details-cell/CL0000126) and [astrocytes](/details-cell/CL0002627), as well as in neurons like [interneurons](/details-cell/CL0000099). Functionally, [RGMA](/details-gene/56963) is deeply involved in pathways regulating nervous system development, including '[Axon guidance](/details-pathway/R-HSA-422475)' and the '[Bmp signaling pathway](/details-go/GO:0030509)', where it plays a key role in neuron projection development and the negative regulation of axon regeneration. ## Cellular Roles and Expression Landscape The expression profile of [RGMA](/details-gene/56963) highlights its profound importance within the central nervous system. **Overall**, it shows the highest significance in various glial cell populations, including [macroglial cell](/details-cell/CL0000126) (CSI: 7.47), [Bergmann glial cell](/details-cell/CL0000644) (CSI: 6.29), and [mature astrocyte](/details-cell/CL0002627) (CSI: 3.88). Its high CSI score in progenitor cells like [radial glial cell](/details-cell/CL0000681) and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) is consistent with a role in neural development. Furthermore, its expression in mature neuronal populations, such as [interneurons](/details-cell/CL0000099), underscores its function in maintaining the architecture of the developed nervous system. Beyond its primary role in the CNS, [RGMA](/details-gene/56963) is also significantly expressed in several non-neuronal cell types. These include mesenchymal and muscle-related cells like [enteric smooth muscle cell](/details-cell/CL0002504), [vascular associated smooth muscle cell](/details-cell/CL0000359), [myofibroblast cell](/details-cell/CL0000186), and [skeletal muscle satellite cell](/details-cell/CL0000594). This broader expression pattern suggests that [RGMA](/details-gene/56963) may participate in developmental and homeostatic processes in various tissues, potentially related to cell guidance, differentiation, and tissue structure. The gene's significant expression in [glioblast](/details-cell/CL0000030) (CSI: 3.72) also points towards a potential role in the pathology of brain tumors. ## Pathways and Molecular Function The functional annotations for [RGMA](/details-gene/56963) are tightly aligned with its role as a guidance molecule and BMP co-receptor. It is a key participant in the Reactome pathway '[Axon guidance](/details-pathway/R-HSA-422475)' and is central to GO biological processes such as '[Neuron projection development](/details-go/GO:0031175)' and '[Negative regulation of axon regeneration](/details-go/GO:0048681)'. This inhibitory role in regeneration is a critical aspect of its function in the mature CNS. Research has shown that [RGMA](/details-gene/56963) can mediate growth cone collapse through pathways involving the inactivation of Ras ([Link](https://doi.org/10.1523/jneurosci.0927-09.2009)). As a BMP co-receptor, [RGMA](/details-gene/56963) is integral to the '[Bmp signaling pathway](/details-go/GO:0030509)', a fundamental pathway in '[Developmental biology](/details-pathway/R-HSA-1266738)'. Its molecular function is defined by its '[Coreceptor activity](/details-go/GO:0015026)' and its ability to engage in '[Protein binding](/details-go/GO:0005515)' with partners like Unc5B to mediate its repulsive effects ([Link](https://doi.org/10.1083/jcb.200807029)). Located on the '[Cell surface](/details-go/GO:0009986)' and '[Plasma membrane](/details-go/GO:0005886)', it is ideally positioned to interpret extracellular cues and translate them into intracellular signals that direct cellular behavior. The gene was first identified and characterized in large-scale cDNA sequencing projects ([Link](https://doi.org/10.1101/gr.gr1547r), [Link](https://doi.org/10.1038/ng1285)). ## Research Directions The established functions of [RGMA](/details-gene/56963) in axon guidance and regeneration, combined with its expression pattern, present several compelling avenues for future research, particularly in neuropathology and oncology. **Proposed Hypotheses:** 1. Given its high expression in [glioblast](/details-cell/CL0000030) and its function in cell guidance, it is hypothesized that [RGMA](/details-gene/56963) signaling is co-opted by glioblastoma cells to promote their migration and invasion into surrounding brain tissue, thereby contributing to the diffuse and aggressive nature of the disease. 2. Based on its annotated role in '[Negative regulation of axon regeneration](/details-go/GO:0048681)' and its high expression in astrocytes, it is hypothesized that [RGMA](/details-gene/56963) is upregulated in reactive astrocytes that form the glial scar following central nervous system injury, creating a non-permissive environment that actively inhibits neuronal repair and functional recovery. **Experimental Approach:** To test the hypothesis regarding glioblastoma, a CRISPR-Cas9 knockout of [RGMA](/details-gene/56963) could be performed in established human glioblastoma cell lines. The effect of the knockout on tumor cell behavior would be assessed using in vitro 3D spheroid invasion assays into a matrix like Matrigel. Furthermore, an orthotopic xenograft mouse model could be employed, where control and [RGMA](/details-gene/56963)-knockout glioblastoma cells are implanted into the brains of immunodeficient mice. Tumor growth, invasion boundaries, and animal survival would be monitored to determine the in vivo contribution of [RGMA](/details-gene/56963) to malignancy. **Therapeutic Potential:** As a cell surface protein, [RGMA](/details-gene/56963) presents a highly accessible target for therapeutic intervention. Its potential roles in both glioblastoma progression and the inhibition of neural repair suggest that strategies centered on **inhibition** would be most beneficial. In the context of glioblastoma, a monoclonal antibody or small molecule inhibitor targeting the [RGMA](/details-gene/56963) receptor complex could potentially reduce tumor cell invasion. In the context of spinal cord injury or stroke, local administration of an [RGMA](/details-gene/56963)-blocking agent could disrupt the inhibitory signals from the glial scar, potentially promoting axon regeneration and improving functional outcomes.

Genular Protein ID: 3076006130

Symbol: RGMA_HUMAN

Name: RGM domain family member A

UniProtKB Accession Codes:

Q96B86 B2RTW1 B7Z5S8 F5GXQ7 F5GZU6 G3V518 Q0JV97 Q8NC80 Q9H0E6 Q9NPM3

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 5 EvolutionaryTrace 1 ExpressionAtlas 1 GO 16 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 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 6 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 19273616

Title: Unc5B associates with LARG to mediate the action of repulsive guidance molecule.

PubMed ID: 19273616

DOI: 10.1083/jcb.200807029

PubMed ID: 19458235

Title: Inactivation of Ras by p120GAP via focal adhesion kinase dephosphorylation mediates RGMa-induced growth cone collapse.

PubMed ID: 19458235

DOI: 10.1523/jneurosci.0927-09.2009

Sequence Information:

  • Length: 450
  • Mass: 49361
  • Checksum: E3244FA591182DCF
  • Sequence:
    • MQPPRERLVV TGRAGWMGMG RGAGRSALGF WPTLAFLLCS FPAATSPCKI LKCNSEFWSA 
TSGSHAPASD DTPEFCAALR SYALCTRRTA RTCRGDLAYH SAVHGIEDLM SQHNCSKDGP 
TSQPRLRTLP PAGDSQERSD SPEICHYEKS FHKHSATPNY THCGLFGDPH LRTFTDRFQT 
CKVQGAWPLI DNNYLNVQVT NTPVLPGSAA TATSKLTIIF KNFQECVDQK VYQAEMDELP 
AAFVDGSKNG GDKHGANSLK ITEKVSGQHV EIQAKYIGTT IVVRQVGRYL TFAVRMPEEV 
VNAVEDWDSQ GLYLCLRGCP LNQQIDFQAF HTNAEGTGAR RLAAASPAPT APETFPYETA 
VAKCKEKLPV EDLYYQACVF DLLTTGDVNF TLAAYYALED VKMLHSNKDK LHLYERTRDL 
PGRAAAGLPL APRPLLGALV PLLALLPVFC

Genular Protein ID: 1088122061

Symbol: A0A0A0MTQ4_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0A0MTQ4

Database IDs:

ARBA 10 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 HGNC 1 InterPro 3 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 4 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

Sequence Information:

  • Length: 458
  • Mass: 50049
  • Checksum: E01D353DC359C163
  • Sequence:
    • MGGLGPRRAG TSRERLVVTG RAGWMGMGRG AGRSALGFWP TLAFLLCSFP AATSPCKILK 
CNSEFWSATS GSHAPASDDT PEFCAALRSY ALCTRRTART CRGDLAYHSA VHGIEDLMSQ 
HNCSKDGPTS QPRLRTLPPA GDSQERSDSP EICHYEKSFH KHSATPNYTH CGLFGDPHLR 
TFTDRFQTCK VQGAWPLIDN NYLNVQVTNT PVLPGSAATA TSKLTIIFKN FQECVDQKVY 
QAEMDELPAA FVDGSKNGGD KHGANSLKIT EKVSGQHVEI QAKYIGTTIV VRQVGRYLTF 
AVRMPEEVVN AVEDWDSQGL YLCLRGCPLN QQIDFQAFHT NAEGTGARRL AAASPAPTAP 
ETFPYETAVA KCKEKLPVED LYYQACVFDL LTTGDVNFTL AAYYALEDVK MLHSNKDKLH 
LYERTRDLPG RAAAGLPLAP RPLLGALVPL LALLPVFC