Details for: LGR6

Gene ID: 59352

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: LGR6

Ensembl ID: ENSG00000133067

Description: leucine rich repeat containing G protein-coupled receptor 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • Bergmann glial cell CL0000644
    CSI 12.15
    rCSI 16.63%
    PRS 98.94
  • myoepithelial cell CL0000185
    CSI 7.28
    rCSI 18.41%
    PRS 99.85
  • cardiac muscle cell CL0000746
    CSI 6.86
    rCSI 9.84%
    PRS 98.62
  • hepatic stellate cell CL0000632
    CSI 6.13
    rCSI 22.96%
    PRS 99.48
  • ependymal cell CL0000065
    CSI 4.53
    rCSI 9.19%
    PRS 96.95
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.87
    rCSI 3.73%
    PRS 99.48
  • renal interstitial pericyte CL1001318
    CSI 3.74
    rCSI 10.31%
    PRS 99.71
  • respiratory basal cell CL0002633
    CSI 3.4
    rCSI 3.53%
    PRS 99.79
  • basal cell of epidermis CL0002187
    CSI 3.25
    rCSI 5.76%
    PRS 92.24
  • tracheobronchial smooth muscle cell CL0019019
    CSI 3.04
    rCSI 5.35%
    PRS 99.82
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.99
    rCSI 2.41%
    PRS 94.22
  • melanocyte of skin CL1000458
    CSI 1.58
    rCSI 2.16%
    PRS 93.75
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.64
    rCSI 3.75%
    PRS 98.39

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [LGR6](/details-gene/59352) (Leucine-rich repeat-containing G-protein coupled receptor 6) is a protein-coding gene located on chromosome 1q32.1. It encodes a transmembrane receptor that is a key component of the Wnt signaling pathway. Functionally, [LGR6](/details-gene/59352) acts as a high-affinity receptor for R-spondins, which are secreted proteins that potentiate Wnt signaling ([Link](https://doi.org/10.1038/nature10337), [Link](https://doi.org/10.1371/journal.pone.0037137)). This role implicates the gene in fundamental biological processes including cell proliferation, migration, and differentiation. **Overall**, expression data highlights [LGR6](/details-gene/59352) as a significant marker in diverse specialized cell types, most notably in [Bergmann glial cells](/details-cell/CL0000644), [myoepithelial cells](/details-cell/CL0000185), and [cardiac muscle cells](/details-cell/CL0000746), suggesting its importance in tissue development, homeostasis, and regeneration across multiple organ systems. ## Cellular Roles and Expression Landscape The expression profile of [LGR6](/details-gene/59352) indicates a highly specific but broad functional role in various tissues. Its most significant expression is observed in [Bergmann glial cells](/details-cell/CL0000644) (CSI: 12.15) of the cerebellum, implying a specialized function in neural support or development. A second major functional cluster includes contractile and structural cells, with high significance in [myoepithelial cells](/details-cell/CL0000185) (CSI: 7.28), [cardiac muscle cells](/details-cell/CL0000746) (CSI: 6.86), and [tracheobronchial smooth muscle cells](/details-cell/CL0019019) (CSI: 3.04). Furthermore, [LGR6](/details-gene/59352) is consistently expressed in several populations of epithelial and progenitor cells, including [fallopian tube secretory epithelial cells](/details-cell/CL4030006), [respiratory basal cells](/details-cell/CL0002633), and [basal cells of the epidermis](/details-cell/CL0002187). This pattern, coupled with its role in the Wnt pathway, strongly suggests a role in maintaining stem cell niches and orchestrating epithelial tissue repair and turnover. Its notable expression in [hepatic stellate cells](/details-cell/CL0000632) (CSI: 6.13) and [renal interstitial pericytes](/details-cell/CL1001318) (CSI: 3.74) also points toward a function in organ fibrosis and tissue remodeling. While its significance is lower in immune and neuronal lineages, detectable expression in subsets like [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) and [corticothalamic-projecting glutamatergic cortical neurons](/details-cell/CL4023013) suggests more nuanced roles in these contexts that are not fully understood. ## Pathways and Molecular Function The functional annotations for [LGR6](/details-gene/59352) converge on its role as a key regulator of the Wnt signaling pathway. As a [G protein-coupled receptor activity](/details-go/GO:0004930) located on the [plasma membrane](/details-go/GO:0005886), its primary function is to mediate extracellular signals. Specifically, it binds R-spondin proteins, which in turn enhances Wnt signaling by preventing the degradation of Wnt co-receptors ([Link](https://doi.org/10.1038/nature10337)). This is reflected in its association with Reactome pathways such as [Signaling by wnt](/details-pathway/R-HSA-195721) and [Tcf dependent signaling in response to wnt](/details-pathway/R-HSA-201681). The downstream effects of [LGR6](/details-gene/59352) activation are broad, encompassing critical biological processes such as [positive regulation of canonical wnt signaling pathway](/details-go/GO:0090263), [cell population proliferation](/details-go/GO:0008283), and [positive regulation of cell migration](/details-go/GO:0030335). Its involvement in [axon guidance](/details-go/GO:0007411) and [bone regeneration](/details-go/GO:1990523) is consistent with the established roles of Wnt signaling in nervous system development and skeletal homeostasis. ## Research Directions The specific expression patterns of [LGR6](/details-gene/59352) across diverse progenitor and specialized cell types, combined with its function as a Wnt signaling modulator, suggest several avenues for future investigation. ### Proposed Hypotheses: 1. Given its exceptionally high significance in [Bergmann glial cells](/details-cell/CL0000644), [LGR6](/details-gene/59352) may be essential for the migration, maturation, or synaptic support functions of these cells during cerebellar development and adult homeostasis. Dysregulation of [LGR6](/details-gene/59352) in this context could contribute to cerebellar ataxia or other neurodevelopmental disorders. 2. The consistent high expression of [LGR6](/details-gene/59352) in basal and myoepithelial cells across multiple tissues (e.g., skin, respiratory tract) suggests it acts as a master regulator of epithelial stem/progenitor cell fate. Loss of [LGR6](/details-gene/59352) function could impair tissue regeneration and wound healing, while its overactivation may contribute to hyperproliferative disorders. ### Experimental Approach: To test the second hypothesis regarding its role in epithelial stem cells, a robust experimental approach would involve organoid models. Specifically, one could generate epidermal or tracheobronchial organoids from primary human cells and use CRISPR-Cas9 to knock out [LGR6](/details-gene/59352). The functional consequences could be assessed by challenging the organoids with injury (e.g., mechanical or chemical) and measuring their regenerative capacity. Readouts would include quantifying organoid formation efficiency, size, and cellular composition through immunofluorescence staining for progenitor (e.g., KRT5/KRT14) and differentiated cell markers. Single-cell RNA sequencing could provide a high-resolution view of how [LGR6](/details-gene/59352) deletion alters cell fate trajectories during regeneration. ### Therapeutic Potential: [LGR6](/details-gene/59352) presents an intriguing therapeutic target. Some studies suggest it may function as a tumor suppressor, particularly in cancers where Wnt signaling is dysregulated ([Link](https://doi.org/10.1371/journal.pone.0037137)). If this holds true, therapeutic strategies would focus on **activation** of the LGR6 pathway. As a cell surface receptor, it is highly amenable to biologic drugs. This could involve the development of activating monoclonal antibodies or engineered R-spondin mimetics to restore or enhance its signaling in specific cancer types. Conversely, in fibrotic diseases where cell types like [hepatic stellate cells](/details-cell/CL0000632) are pathologically activated, **inhibition** of [LGR6](/details-gene/59352) could be a viable anti-fibrotic strategy.

Genular Protein ID: 1849295926

Symbol: LGR6_HUMAN

Name: Leucine-rich repeat-containing G-protein coupled receptor 6

UniProtKB Accession Codes:

Q9HBX8 Q5T509 Q5T512 Q6UY15 Q86VU0 Q96K69 Q9BYD7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 3 ExpressionAtlas 1 GO 16 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 3 SMART 4 SMR 1 STRING 1 SUPFAM 3 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10935549

Title: The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7.

PubMed ID: 10935549

DOI: 10.1210/mend.14.8.0510

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: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 12044878

Title: Identification of G protein-coupled receptor genes from the human genome sequence.

PubMed ID: 12044878

DOI: 10.1016/s0014-5793(02)02775-8

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 21727895

Title: Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.

PubMed ID: 21727895

DOI: 10.1038/nature10337

PubMed ID: 22615920

Title: LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor.

PubMed ID: 22615920

DOI: 10.1371/journal.pone.0037137

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 967
  • Mass: 104298
  • Checksum: 22E332E85DF8DCE0
  • Sequence:
    • MPSPPGLRAL WLCAALCASR RAGGAPQPGP GPTACPAPCH CQEDGIMLSA DCSELGLSAV 
PGDLDPLTAY LDLSMNNLTE LQPGLFHHLR FLEELRLSGN HLSHIPGQAF SGLYSLKILM 
LQNNQLGGIP AEALWELPSL QSLRLDANLI SLVPERSFEG LSSLRHLWLD DNALTEIPVR 
ALNNLPALQA MTLALNRISH IPDYAFQNLT SLVVLHLHNN RIQHLGTHSF EGLHNLETLD 
LNYNKLQEFP VAIRTLGRLQ ELGFHNNNIK AIPEKAFMGN PLLQTIHFYD NPIQFVGRSA 
FQYLPKLHTL SLNGAMDIQE FPDLKGTTSL EILTLTRAGI RLLPSGMCQQ LPRLRVLELS 
HNQIEELPSL HRCQKLEEIG LQHNRIWEIG ADTFSQLSSL QALDLSWNAI RSIHPEAFST 
LHSLVKLDLT DNQLTTLPLA GLGGLMHLKL KGNLALSQAF SKDSFPKLRI LEVPYAYQCC 
PYGMCASFFK ASGQWEAEDL HLDDEESSKR PLGLLARQAE NHYDQDLDEL QLEMEDSKPH 
PSVQCSPTPG PFKPCEYLFE SWGIRLAVWA IVLLSVLCNG LVLLTVFAGG PVPLPPVKFV 
VGAIAGANTL TGISCGLLAS VDALTFGQFS EYGARWETGL GCRATGFLAV LGSEASVLLL 
TLAAVQCSVS VSCVRAYGKS PSLGSVRAGV LGCLALAGLA AALPLASVGE YGASPLCLPY 
APPEGQPAAL GFTVALVMMN SFCFLVVAGA YIKLYCDLPR GDFEAVWDCA MVRHVAWLIF 
ADGLLYCPVA FLSFASMLGL FPVTPEAVKS VLLVVLPLPA CLNPLLYLLF NPHFRDDLRR 
LRPRAGDSGP LAYAAAGELE KSSCDSTQAL VAFSDVDLIL EASEAGRPPG LETYGFPSVT 
LISCQQPGAP RLEGSHCVEP EGNHFGNPQP SMDGELLLRA EGSTPAGGGL SGGGGFQPSG 
LAFASHV