Details for: RGS21

Gene ID: 431704

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: RGS21

Ensembl ID: ENSG00000253148

Description: regulator of G protein signaling 21

Selected Context(s):  Overall

Cell Significance Landscape

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Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 8.57
    rCSI 17.39%
    PRS 99.76

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.
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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 Regulator of G-protein signaling 21 ([RGS21](/details-gene/431704)) is a protein-coding gene located on chromosome 1q31.2. As a member of the RGS protein family, its primary function is to negatively regulate G protein-coupled receptor (GPCR) signaling pathways by acting as a GTPase-activating protein (GAP) for G alpha subunits. Functionally, it is implicated in diverse processes ranging from the sensory perception of taste to the broader modulation of G alpha (i) and G alpha (q) signaling events. **Overall**, expression data indicates that [RGS21](/details-gene/431704) is a highly significant marker for [ependymal cells](/details-cell/CL0000065), suggesting a specialized role within the central nervous system. ## Cellular Roles and Expression Landscape The expression profile of [RGS21](/details-gene/431704) points towards a highly specialized function. **Overall**, the gene shows its most significant expression in [ependymal cells](/details-cell/CL0000065) (CSI: 8.57), the epithelial-like cells that line the ventricles of the brain and the central canal of the spinal cord. This specific expression pattern was also noted in early characterization studies of the gene ([Link](https://pubmed.ncbi.nlm.nih.gov/16302027)). The high significance in this cell type suggests that [RGS21](/details-gene/431704) is not a broadly expressed signaling regulator but rather serves a distinct purpose within the unique environment of the cerebrospinal fluid (CSF) interface. ## Pathways and Molecular Function The functional annotations for [RGS21](/details-gene/431704) are consistent with its identity as an RGS protein. It is a key participant in the [G protein-coupled receptor signaling pathway](/details-go/GO:0007186) and acts to negatively regulate signal transduction ([GO:0009968](/details-go/GO:0009968)). Its molecular function as a GTPase activator is central to this role ([GO:0003924](/details-go/GO:0003924)). At the pathway level, [RGS21](/details-gene/431704) is involved in multiple Reactome pathways related to GPCR signaling, including [Gpcr downstream signalling](/details-reactome/R-HSA-388396), specifically modulating [G alpha (i) signalling events](/details-reactome/R-HSA-418594) and [G alpha (q) signalling events](/details-reactome/R-HSA-416476). Interestingly, it is also annotated for sensory perception, including bitter ([GO:0050913](/details-go/GO:0050913)), sweet ([GO:0050916](/details-go/GO:0050916)), and umami taste ([GO:0050917](/details-go/GO:0050917)), highlighting its role in highly specialized GPCR systems. Its localization to the [plasma membrane](/details-go/GO:0005886) is critical for its function in intercepting and deactivating G protein subunits at the site of signal reception. ## Research Directions The specific and high-level expression of [RGS21](/details-gene/431704) in [ependymal cells](/details-cell/CL0000065) provides a strong foundation for targeted research into its role in central nervous system homeostasis and pathology. **Proposed Hypotheses:** 1. [RGS21](/details-gene/431704) functions as a key regulator of ependymal ciliary beat frequency by modulating GPCR pathways that respond to signaling molecules (e.g., purines, monoamines) present in the cerebrospinal fluid. 2. Given its role in chemosensation (taste), [RGS21](/details-gene/431704) may be part of a sensory apparatus in [ependymal cells](/details-cell/CL0000065) that detects changes in CSF composition, such as pH, glucose, or inflammatory mediators, thereby influencing brain homeostasis. 3. Dysregulation of [RGS21](/details-gene/431704) activity in [ependymal cells](/details-cell/CL0000065) could contribute to the pathogenesis of hydrocephalus or neuroinflammatory conditions by altering CSF dynamics or the glial response to injury. **Experimental Approach:** To test the hypothesis that [RGS21](/details-gene/431704) modulates ependymal chemosensory functions (Hypothesis 2), one could employ an *in vitro* model using primary ependymal cell cultures or iPSC-derived ependymal-like cells. Using CRISPR-Cas9 to knock out [RGS21](/details-gene/431704) in these cells, researchers could then perform calcium imaging or FRET-based biosensor assays to measure downstream G alpha (q) or G alpha (i) signaling in response to a panel of CSF-relevant ligands (e.g., ATP, serotonin, lactate). A blunted or exaggerated signaling response in the knockout cells compared to wild-type controls would provide direct evidence of its modulatory role. **Therapeutic Potential:** The highly restricted expression of [RGS21](/details-gene/431704) in [ependymal cells](/details-cell/CL0000065) makes it an attractive therapeutic target. If its dysregulation is linked to neurological disorders involving CSF imbalance or neuroinflammation, developing specific modulators could offer a focused therapeutic strategy with a reduced risk of off-target effects in other brain cells like neurons or astrocytes. Depending on the disease mechanism, either small-molecule inhibitors or allosteric activators of [RGS21](/details-gene/431704) could be pursued to restore normal GPCR signaling tone at the brain-CSF interface.

Genular Protein ID: 3099048245

Symbol: RGS21_HUMAN

Name: Regulator of G-protein signaling 21

UniProtKB Accession Codes:

Q2M5E4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 2 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 16302027

Title: Isolation and expression pattern of RGS21 gene, a novel RGS member.

PubMed ID: 16302027

Sequence Information:

  • Length: 152
  • Mass: 17671
  • Checksum: D9EF097E89CA9731
  • Sequence:
    • MPVKCCFYRS PTAETMTWSE NMDTLLANQA GLDAFRIFLK SEFSEENVEF WLACEDFKKT 
KNADKIASKA KMIYSEFIEA DAPKEINIDF GTRDLISKNI AEPTLKCFDE AQKLIYCLMA 
KDSFPRFLKS EIYKKLVNSQ QVPNHKKWLP FL