Details for: GPR15LG

Gene ID: 387695

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: GPR15LG

Ensembl ID: ENSG00000188373

Description: G protein-coupled receptor 15 ligand

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • colon epithelial cell CL0011108
    CSI 44.59
    rCSI 46.71%
    PRS 97.05
  • enterocyte CL0000584
    CSI 23.41
    rCSI 37.74%
    PRS 95.98
  • innate lymphoid cell CL0001065
    CSI 23.16
    rCSI 47.83%
    PRS 93.05
  • intestine goblet cell CL0019031
    CSI 22.7
    rCSI 20.15%
    PRS 96.91
  • IgA plasma cell CL0000987
    CSI 19.8
    rCSI 20.27%
    PRS 96.27
  • conventional dendritic cell CL0000990
    CSI 18.8
    rCSI 15.7%
    PRS 92.44
  • transit amplifying cell of colon CL0009011
    CSI 17.73
    rCSI 20.83%
    PRS 98.1
  • goblet cell CL0000160
    CSI 16.45
    rCSI 15.55%
    PRS 96.89
  • chondrocyte CL0000138
    CSI 14.95
    rCSI 23.77%
    PRS 95.95
  • intestinal epithelial cell CL0002563
    CSI 13.79
    rCSI 14.41%
    PRS 96.73
  • helper T cell CL0000912
    CSI 11.32
    rCSI 16.01%
    PRS 93.68
  • enterocyte of epithelium of large intestine CL0002071
    CSI 10.92
    rCSI 57.34%
    PRS 98.13
  • basal cell of epidermis CL0002187
    CSI 9.69
    rCSI 17.18%
    PRS 79.79
  • intestinal crypt stem cell of colon CL0009043
    CSI 9.24
    rCSI 69.41%
    PRS 98.89
  • colon goblet cell CL0009039
    CSI 8.91
    rCSI 21.19%
    PRS 97.92
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 7.84
    rCSI 9.5%
    PRS 85.25
  • melanocyte of skin CL1000458
    CSI 7.76
    rCSI 10.58%
    PRS 80.86
  • BEST4+ enteroycte CL4030026
    CSI 6.7
    rCSI 8.33%
    PRS 97.23
  • suprabasal keratinocyte CL4033013
    CSI 6.14
    rCSI 10.01%
    PRS 81.34
  • transit amplifying cell CL0009010
    CSI 5.75
    rCSI 8.79%
    PRS 98.51
  • type L enteroendocrine cell CL0002279
    CSI 3.77
    rCSI 7.08%
    PRS 97.57
  • cytotoxic T cell CL0000910
    CSI 3.45
    rCSI 19.76%
    PRS 95.06
  • enteroendocrine cell of colon CL0009042
    CSI 2.66
    rCSI 12.49%
    PRS 97.31
  • paneth cell of colon CL0009009
    CSI 2.53
    rCSI 24.87%
    PRS 98.25
  • colonocyte CL1000347
    CSI 2.09
    rCSI 2.99%
    PRS 97

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 [GPR15LG](/details-gene/387695), also known as C10orf99, is a secreted protein that functions as the specific ligand for the G protein-coupled receptor GPR15. It plays a crucial role at the interface of epithelial biology and mucosal immunity, acting as a chemokine that modulates lymphocyte recruitment to epithelial tissues. **Overall**, expression data reveals its highest significance in the epithelial lining of the colon, particularly in [colon epithelial cells](/details-cell/CL0011108), as well as in various resident immune cell populations. Functionally, [GPR15LG](/details-gene/387695) is implicated in T cell homeostasis, antimicrobial defense, and the regulation of epithelial cell proliferation, with emerging roles in inflammatory conditions such as psoriasis and colon cancer ([Link](https://doi.org/10.3389/fimmu.2017.01111), [Link](https://doi.org/10.1038/srep06812)). ## Cellular Roles and Expression Landscape The expression profile of [GPR15LG](/details-gene/387695) highlights its specialized function in maintaining homeostasis and coordinating immune responses at mucosal and cutaneous barriers. The gene's highest significance is observed in the gastrointestinal tract, with profound expression in [colon epithelial cells](/details-cell/CL0011108) (CSI: 44.59), [enterocytes](/details-cell/CL0000584) (CSI: 23.41), and [intestine goblet cells](/details-cell/CL0019031) (CSI: 22.70). Its expression extends to progenitor populations, including [transit amplifying cells of the colon](/details-cell/CL0009011) and [intestinal crypt stem cells of the colon](/details-cell/CL0009043), suggesting a fundamental role in the continuous renewal and function of the colonic epithelium. In parallel, [GPR15LG](/details-gene/387695) is a significant marker for several immune cell types that are often tissue-resident or trafficked to epithelial sites. These include [innate lymphoid cells](/details-cell/CL0001065) (CSI: 23.16), [IgA plasma cells](/details-cell/CL0000987) (CSI: 19.80), [conventional dendritic cells](/details-cell/CL0000990) (CSI: 18.80), and [helper T cells](/details-cell/CL0000912) (CSI: 11.32). This dual expression pattern in both epithelial and immune cells underscores its role as a key communicator that orchestrates lymphocyte trafficking to the gut and other barrier tissues. Notably, its expression in [basal cells of the epidermis](/details-cell/CL0002187) is consistent with its described role in skin inflammatory diseases ([Link](https://doi.org/10.1038/s41598-018-26996-z)). ## Pathways and Molecular Function The molecular functions of [GPR15LG](/details-gene/387695) are tightly linked to its role as a secreted signaling molecule. As an extracellular protein, it primarily exerts its effects through `Receptor ligand activity` ([GO:0048018](https://www.ebi.ac.uk/QuickGO/term/GO:0048018)) and `G protein-coupled receptor binding` ([GO:0001664](https://www.ebi.ac.uk/QuickGO/term/GO:0001664)), specifically engaging the GPR15 receptor. This interaction triggers downstream signaling pathways that are central to immune cell migration. Consistent with its high expression in immune cells and its identification as a chemokine ([Link](https://doi.org/10.3389/fimmu.2017.01111)), [GPR15LG](/details-gene/387695) is annotated with functions such as `Lymphocyte chemotaxis` ([GO:0048247](https://www.ebi.ac.uk/QuickGO/term/GO:0048247)) and `Regulation of t cell migration` ([GO:2000404](https://www.ebi.ac.uk/QuickGO/term/GO:2000404)). Beyond its chemotactic properties, research has demonstrated that it also possesses antimicrobial capabilities, reflected in its association with `Defense response to fungus` ([GO:0050832](https://www.ebi.ac.uk/QuickGO/term/GO:0050832)) and `Defense response to gram-positive bacterium` ([GO:0050830](https://www.ebi.ac.uk/QuickGO/term/GO:0050830)) ([Link](https://doi.org/10.1016/j.bbrc.2014.12.115)). Furthermore, its involvement in `Regulation of keratinocyte proliferation` ([GO:0010837](https://www.ebi.ac.uk/QuickGO/term/GO:0010837)) and `Negative regulation of cell division` ([GO:0051782](https://www.ebi.ac.uk/QuickGO/term/GO:0051782)) aligns with its documented roles in skin pathologies and its potential as a tumor suppressor in colon cancer ([Link](https://doi.org/10.1038/srep06812)). ## Research Directions The dichotomous role of [GPR15LG](/details-gene/387695) in both promoting inflammatory responses and suppressing tumor growth presents intriguing avenues for future research. Its function appears highly context-dependent, acting as a homeostatic regulator in healthy tissue but potentially contributing to pathology when dysregulated. Based on the available data, several testable hypotheses can be proposed: 1. Given its high expression in the colonic epithelium and its reported ability to inhibit colon cancer cell growth ([Link](https://doi.org/10.1038/srep06812)), it can be hypothesized that epigenetic silencing or mutational inactivation of [GPR15LG](/details-gene/387695) in intestinal epithelial cells is a key event in early colorectal carcinogenesis. This loss would disrupt local T cell surveillance mediated by the GPR15/GPR15LG axis and remove a critical brake on epithelial proliferation. 2. Considering its role in promoting keratinocyte proliferation in psoriasis ([Link](https://doi.org/10.1038/s41598-018-26996-z)) and its recently identified function as an epithelial-derived pruritogen (itch-inducer) ([Link](https://doi.org/10.1126/sciadv.abm7342)), it is hypothesized that [GPR15LG](/details-gene/387695) is a central mediator of the itch-scratch cycle in chronic inflammatory skin diseases. In this model, epidermal [GPR15LG](/details-gene/387695) would not only recruit pathogenic GPR15+ T cells but also directly activate sensory neurons to perpetuate inflammation and pruritus. A key experiment to test the first hypothesis would involve the use of a colon-specific conditional knockout mouse model (e.g., *Gpr15lg*flox/flox; Villin-CreERT2). Following tamoxifen-induced deletion of [GPR15LG](/details-gene/387695) in the intestinal epithelium, mice could be subjected to a colitis-associated cancer model (e.g., AOM/DSS). Tumor burden, progression, and the composition of the tumor immune microenvironment (specifically the infiltration of GPR15-expressing T cells) could then be assessed using histology, flow cytometry, and single-cell RNA sequencing. Therapeutically, [GPR15LG](/details-gene/387695) presents a dual-natured target. For inflammatory skin conditions like psoriasis or atopic dermatitis, **inhibition** of [GPR15LG](/details-gene/387695) is a promising strategy. As a secreted protein, it is an excellent candidate for neutralization by a monoclonal antibody, which could simultaneously block T cell infiltration and alleviate itch. Conversely, in the context of colorectal cancer, therapeutic **activation** or supplementation may be beneficial. A recombinant [GPR15LG](/details-gene/387695) protein or a small molecule designed to enhance its production could potentially restore anti-tumor immunity and suppress malignant cell growth.

Genular Protein ID: 2854752941

Symbol: GP15L_HUMAN

Name: Secreted protein C10orf99

UniProtKB Accession Codes:

Q6UWK7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 GO 15 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 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 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 15164054

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

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 25351403

Title: CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest.

PubMed ID: 25351403

DOI: 10.1038/srep06812

PubMed ID: 25585381

Title: AP-57/C10orf99 is a new type of mutifunctional antimicrobial peptide.

PubMed ID: 25585381

DOI: 10.1016/j.bbrc.2014.12.115

PubMed ID: 28936214

Title: A mucosal and cutaneous chemokine ligand for the lymphocyte chemoattractant receptor GPR15.

PubMed ID: 28936214

DOI: 10.3389/fimmu.2017.01111

PubMed ID: 28900043

Title: A natural ligand for the orphan receptor GPR15 modulates lymphocyte recruitment to epithelia.

PubMed ID: 28900043

DOI: 10.1126/scisignal.aal0180

PubMed ID: 29872130

Title: C10orf99 contributes to the development of psoriasis by promoting the proliferation of keratinocytes.

PubMed ID: 29872130

DOI: 10.1038/s41598-018-26996-z

PubMed ID: 35704588

Title: GPR15L is an epithelial inflammation-derived pruritogen.

PubMed ID: 35704588

DOI: 10.1126/sciadv.abm7342

Sequence Information:

  • Length: 81
  • Mass: 9173
  • Checksum: 276E720364160B8A
  • Sequence:
    • MRLLVLSSLL CILLLCFSIF STEGKRRPAK AWSGRRTRLC CHRVPSPNST NLKGHHVRLC 
KPCKLEPEPR LWVVPGALPQ V