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    LGR5 leucine rich repeat containing G protein-coupled receptor 5 [ Homo sapiens (human) ]

    Gene ID: 8549, updated on 27-Nov-2024

    Summary

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    Official Symbol
    LGR5provided by HGNC
    Official Full Name
    leucine rich repeat containing G protein-coupled receptor 5provided by HGNC
    Primary source
    HGNC:HGNC:4504
    See related
    Ensembl:ENSG00000139292 MIM:606667; AllianceGenome:HGNC:4504
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FEX; HG38; GPR49; GPR67; GRP49
    Summary
    The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
    Expression
    Biased expression in placenta (RPKM 11.9), small intestine (RPKM 3.2) and 8 other tissues See more
    Orthologs
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    Genomic context

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    See LGR5 in Genome Data Viewer
    Location:
    12q21.1
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (71439129..71586310)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (71416272..71563815)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (71833578..71980090)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369831 Neighboring gene uncharacterized LOC105369832 Neighboring gene NANOG hESC enhancer GRCh37_chr12:71675819-71676351 Neighboring gene MPRA-validated peak1815 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:71751260-71751760 Neighboring gene Sharpr-MPRA regulatory region 3574 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4657 Neighboring gene uncharacterized LOC124902962 Neighboring gene MPRA-validated peak1816 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr12:71914915-71915416 Neighboring gene uncharacterized LOC105369833 Neighboring gene MPRA-validated peak1818 silencer Neighboring gene uncharacterized LOC124902963 Neighboring gene uncharacterized LOC124902964 Neighboring gene MPRA-validated peak1819 silencer Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr12:71985323-71985838 Neighboring gene MPRA-validated peak1820 silencer Neighboring gene small nucleolar RNA SNORA17 Neighboring gene zinc finger C3H1-type containing

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Logarithmic expansion of LGR5(+) cells in human colorectal cancer. Martin ML, et al. Cell Signal, 2018 Jan. PMID 28958617, Free PMC Article
    2. Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer. Xi HQ, et al. Br J Cancer, 2014 Apr 15. PMID 24594994, Free PMC Article
    3. Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche. Cervelló I, et al. Fertil Steril, 2017 Feb. PMID 27887719
    4. Intestinal stem cell marker LGR5 expression during gastric carcinogenesis. Zheng ZX, et al. World J Gastroenterol, 2013 Dec 14. PMID 24379591, Free PMC Article
    5. Inhibiting clathrin-mediated endocytosis of the leucine-rich G protein-coupled receptor-5 diminishes cell fitness. Snyder JC, et al. J Biol Chem, 2017 Apr 28. PMID 28275053, Free PMC Article

    See all (217) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genome-Wide Association Study Identifies 4 Novel Risk Loci for Small Intestinal Neuroendocrine Tumors Including a Missense Mutation in LGR5.
      Title: Genome-Wide Association Study Identifies 4 Novel Risk Loci for Small Intestinal Neuroendocrine Tumors Including a Missense Mutation in LGR5.
    2. Detecting rare thalassemia in children with anemia using third-generation sequencing.
      Title: Detecting rare thalassemia in children with anemia using third-generation sequencing.
    3. The Expression of Stem Cell Marker LGR5 and Its Coexpression with Beta-Catenin in Sporadic Colorectal Carcinoma and Adenoma: A Comparative Immunohistochemical Study.
      Title: The Expression of Stem Cell Marker LGR5 and Its Coexpression with Β-Catenin in Sporadic Colorectal Carcinoma and Adenoma: A Comparative Immunohistochemical Study.
    4. Evaluation of LGR5 Cancer Stem Cell Marker Expression in Breast Cancer and Its Relationship with Hormonal Profile and Clinical Pathological Features.
      Title: Evaluation of LGR5 Cancer Stem Cell Marker Expression in Breast Cancer and Its Relationship with Hormonal Profile and Clinical Pathological Features.
    5. TCF7L1 Regulates LGR5 Expression in Colorectal Cancer Cells.
      Title: TCF7L1 Regulates LGR5 Expression in Colorectal Cancer Cells.
    6. Elevated Expression of LGR5 and WNT Signaling Factors in Neuroblastoma Cells With Acquired Drug Resistance.
      Title: Elevated Expression of LGR5 and WNT Signaling Factors in Neuroblastoma Cells With Acquired Drug Resistance.
    7. LGR5 promotes invasion and migration by regulating YAP activity in hypopharyngeal squamous cell carcinoma cells under inflammatory condition.
      Title: LGR5 promotes invasion and migration by regulating YAP activity in hypopharyngeal squamous cell carcinoma cells under inflammatory condition.
    8. LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.
      Title: LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.
    9. Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis.
      Title: Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis.
    10. Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer.
      Title: Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (187)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
    EBI GWAS Catalog
    Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC117008

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    NOT enables G protein-coupled receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-hormone receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables transmembrane signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in epithelial cell proliferation involved in renal tubule morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hair follicle development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inner ear development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in oocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of canonical Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in trans-Golgi network membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    leucine-rich repeat-containing G-protein coupled receptor 5
    Names
    G-protein coupled receptor 49
    G-protein coupled receptor 67
    G-protein coupled receptor HG38
    orphan G protein-coupled receptor HG38

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001277226.2 → NP_001264155.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001264155.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC078860, BC096325, CA412916, DR003044
      Consensus CDS
      CCDS61194.1
      UniProtKB/Swiss-Prot
      O75473
      Related
      ENSP00000441035.2, ENST00000540815.2
      Conserved Domains (7) summary
      smart00013
      Location:33 → 70
      LRRNT; Leucine rich repeat N-terminal domain
      PLN00113
      Location:71 → 360
      PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional
      sd00031
      Location:306 → 329
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:68 → 91
      LRR_RI; leucine-rich repeat [structural motif]
      pfam13855
      Location:351 → 430
      LRR_8; Leucine rich repeat
      cd14964
      Location:536 → 560
      7tm_GPCRs; TM helix 1 [structural motif]
      cl28897
      Location:534 → 807
      7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

    2. NM_001277227.2 → NP_001264156.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001264156.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC078860, CA412916, DR003044, FN820440
      Consensus CDS
      CCDS61195.1
      UniProtKB/Swiss-Prot
      O75473
      Related
      ENSP00000443033.1, ENST00000536515.5
      Conserved Domains (6) summary
      smart00013
      Location:33 → 70
      LRRNT; Leucine rich repeat N-terminal domain
      PLN00113
      Location:71 → 312
      PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional
      sd00031
      Location:47 → 67
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:68 → 91
      LRR_RI; leucine-rich repeat [structural motif]
      cd15363
      Location:486 → 759
      7tmA_LGR5; leucine-rich repeats-containing G protein-coupled receptor 5, member of the class A family of seven-transmembrane G protein-coupled receptors
      pfam13855
      Location:303 → 382
      LRR_8; Leucine rich repeat

    3. NM_003667.4 → NP_003658.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform 1 precursor

      See identical proteins and their annotated locations for NP_003658.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC078860, AF062006, CA412916, DR003044
      Consensus CDS
      CCDS9000.1
      UniProtKB/Swiss-Prot
      D8MCT0, O75473, Q4VAM0, Q4VAM2, Q9UP75
      UniProtKB/TrEMBL
      A0A0A8K8C7
      Related
      ENSP00000266674.4, ENST00000266674.10
      Conserved Domains (5) summary
      smart00013
      Location:33 → 70
      LRRNT; Leucine rich repeat N-terminal domain
      PLN00113
      Location:71 → 426
      PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional
      sd00031
      Location:307 → 353
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:68 → 91
      LRR_RI; leucine-rich repeat [structural motif]
      cd15363
      Location:558 → 831
      7tmA_LGR5; leucine-rich repeats-containing G protein-coupled receptor 5, member of the class A family of seven-transmembrane G protein-coupled receptors

    RNA

    1. NR_110596.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has an alternate 3' structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC078860, AK075399, AK294985, BQ774570, DA811892, DR003044, H88004
      Related
      ENST00000550851.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      71439129..71586310
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047429800.1 → XP_047285756.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform X1

    2. XM_047429801.1 → XP_047285757.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      71416272..71563815
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054373692.1 → XP_054229667.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform X1

    2. XM_054373693.1 → XP_054229668.1  leucine-rich repeat-containing G-protein coupled receptor 5 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75473.1 GenPept UniProtKB/Swiss-Prot:O75473

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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