Details for: GPRIN2

Gene ID: 9721

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: GPRIN2

Ensembl ID: ENSG00000204175

Description: G protein regulated inducer of neurite outgrowth 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 4.05
    rCSI 3.82%
    PRS 98.53
  • intestine goblet cell CL0019031
    CSI 3.23
    rCSI 2.87%
    PRS 98.41
  • small intestine goblet cell CL1000495
    CSI 1.94
    rCSI 4.25%
    PRS 99.05

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • 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 [GPRIN2](/details-gene/9721), or G protein regulated inducer of neurite outgrowth 2, is a protein-coding gene located on chromosome 10q11.22. Despite its name, which originates from early studies on its role in [neuron projection development](/details-ontology/GO:0031175) ([Link](https://pubmed.ncbi.nlm.nih.gov/10480904/)), expression data indicates its most significant role is as a highly specific marker for [goblet cells](/details-cell/CL0000160) within the intestine. Functionally, it is annotated as a [plasma membrane](/details-ontology/GO:0005886) protein involved in [protein binding](/details-ontology/GO:0005515), suggesting it participates in cell signaling complexes at the cell surface, potentially translating extracellular signals into changes in cell morphology or secretory function. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [GPRIN2](/details-gene/9721) is dominated by its high significance in the secretory epithelial lineage of the gastrointestinal tract. It is a top marker for [goblet cell](/details-cell/CL0000160) (CSI: 4.05), [intestine goblet cell](/details-cell/CL0019031) (CSI: 3.23), and [small intestine goblet cell](/details-cell/CL1000495) (CSI: 1.94). This strong and specific expression signature suggests a crucial function in the maintenance, maturation, or secretory activity of these mucus-producing cells. The gene was originally identified from brain cDNA libraries, leading to its characterization in the context of neuronal development ([Link](https://pubmed.ncbi.nlm.nih.gov/9628581/), [Link](https://pubmed.ncbi.nlm.nih.gov/10480904/)). However, its profound enrichment in intestinal [goblet cells](/details-cell/CL0000160) suggests that its function may be broader than initially described, possibly involving a general role in regulating polarized cell morphology and exocytosis that is adapted for different purposes in distinct cell types—neurite outgrowth in neurons and mucus secretion in goblet cells. ## Pathways and Molecular Function The established functional annotations for [GPRIN2](/details-gene/9721) provide a framework for its potential mechanism of action. * **Biological Process:** Its involvement in [neuron projection development](/details-ontology/GO:0031175) suggests a role in cytoskeletal organization and cell morphogenesis. In the context of [goblet cells](/details-cell/CL0000160), this function could be repurposed to control the complex process of mucin granule trafficking and exocytosis at the apical membrane. * **Molecular Function:** The annotation for [protein binding](/details-ontology/GO:0005515) is consistent with its identity as a G-protein regulated molecule, implying it serves as an effector or scaffold protein within a larger signaling complex. * **Cellular Component:** Its localization to the [plasma membrane](/details-ontology/GO:0005886) positions it to respond to extracellular or luminal signals, transducing them via G-protein pathways to regulate intracellular processes critical for goblet cell function. ## Research Directions The striking discrepancy between the gene's name and its primary expression pattern in [goblet cells](/details-cell/CL0000160) opens several avenues for future investigation. ### Testable Hypotheses 1. [GPRIN2](/details-gene/9721) is a critical mediator of G-protein coupled receptor (GPCR) signaling in intestinal [goblet cells](/details-cell/CL0000160), regulating the final stages of mucin granule exocytosis and contributing to the formation of the protective mucus barrier. 2. The function of [GPRIN2](/details-gene/9721) in "neurite outgrowth" is a specific instance of a more fundamental role in promoting polarized membrane extension and secretion, a process essential for both axon guidance in neurons and apical mucus release in [goblet cells](/details-cell/CL0000160). ### Key Experiments To test the hypothesis that [GPRIN2](/details-gene/9721) regulates goblet cell secretion, one could utilize CRISPR-Cas9 to knock out the gene in human intestinal organoids. The impact on goblet cell function could be assessed by stimulating these organoids with GPCR agonists (e.g., carbachol) and measuring subsequent mucin-2 (MUC2) secretion via ELISA. Immunofluorescence staining for MUC2 and electron microscopy could further determine if the loss of [GPRIN2](/details-gene/9721) affects goblet cell differentiation, morphology, or the docking and fusion of mucin granules at the apical membrane. ### Therapeutic Potential Given its highly specific expression in intestinal [goblet cells](/details-cell/CL0000160), [GPRIN2](/details-gene/9721) presents an intriguing therapeutic target for diseases involving dysfunctional mucosal barriers or aberrant mucus production, such as inflammatory bowel disease (IBD) or mucinous adenocarcinomas. For conditions characterized by a depleted mucus layer, such as ulcerative colitis, a therapeutic strategy might involve activating the [GPRIN2](/details-gene/9721) pathway to enhance mucosal protection. Conversely, in mucus-overproducing cancers, targeted inhibition could be beneficial. Its localization at the plasma membrane makes it a potentially tractable target for orally-delivered, gut-restricted small molecules or biologics.

Genular Protein ID: 270950708

Symbol: GRIN2_HUMAN

Name: G protein-regulated inducer of neurite outgrowth 2

UniProtKB Accession Codes:

O60269 Q5SVF0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 GO 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 3 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9628581

Title: Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9628581

DOI: 10.1093/dnares/5.1.31

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 10480904

Title: A candidate target for G protein action in brain.

PubMed ID: 10480904

DOI: 10.1074/jbc.274.38.26931

Sequence Information:

  • Length: 458
  • Mass: 47450
  • Checksum: D6395C187FAD142D
  • Sequence:
    • MSSSRPEPGP WAPLSPRLQP LSQSSSSLLG EGREQRPELR KTASSTVWQA QLGEASTRPQ 
APEEEGNPPE SMKPARASGP KARPSAGGHW WSSTVGNVST MGGSDLCRLR APSAAAMQRS 
HSDLVRSTQM RGHSGARKAS LSCSALGSSP VHRAQLQPGG TSGQGGQAPA GLERDLAPED 
ETSNSAWMLG ASQLSVPPLD LGDTTAHSSS AQAEPKAAEQ LATTTCHALP PAALLCGMRE 
VRAGGCCHAL PATGILAFPK LVASVSESGL QAQHGVKIHC RLSGGLPGHS HCCAHLWGPA 
GLVPEPGSRT KDVWTMTSAN DLAPAEASPL SAQDAGVQAA PVAACKAVAT SPSLEAPAAL 
HVFPEVTLGS SLEEVPSPVR DVRWDAEGMT WEVYGAAVDL EVLGVAIQKH LEMQFEQLQR 
APASEDSLSV EGRRGPLRAV MQSLRRPSCC GCSGAAPE