.. _LGR5: LGR5 ^^^^ .. contents:: :local: General Information ******************* :Full gene name: leucine-rich repeat containing G protein-coupled receptor 5 :Entrez Gene ID: 8549 :Location: 12q22-q23 :Synonyms: GPR67, GRP49, HG38, FEX, GPR49 :Type: protein-coding User SNPs ********* SNPs given by the user that are near or inside this gene: +-----------+---------------+-----------+ | SNP | Distance (bp) | Direction | +===========+===============+===========+ | rs7961581 | 170711 | upstream | +-----------+---------------+-----------+ .. _LGR5 Gene summary: NCBI Summary ************ None available. .. _OMIM ID 606667 : http://omim.org/entry/606667 .. _LGR5 OMIM Text: OMIM **** :OMIM ID: `OMIM ID 606667 `_ .. _LGR5 Phenotype: NCBI Phenotypes *************** * Twelve type 2 \ ``diabetes``\ susceptibility loci identified through large-scale association analysis. * NHGRI GWA Catalog * Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 \ ``diabetes``\ . .. _LGR5 GO Term: Gene Ontology ************* * G-protein coupled receptor signaling pathway * protein-hormone receptor activity * G-protein coupled receptor activity * inner ear development * integral to plasma membrane .. _LGR5 Pathway: KEGG Pathways ************* * `Neuroactive ligand-receptor interaction `_ .. _LGR5 GeneRIF: GeneRIFs ******** * Lgr5 expression detected in 70% of BE cases and between 90 and 100% of advanced dysplastic lesions and EAC. Lgr5 has potential utility as biomarker for BE-associated dysplasia and EAC. [`PMID 19549212`_] * High level of LGR5 expression was associated with colorectal cancer. [`PMID 21125339`_] * Lgr5 is a potential marker of intestinal stem cells in humans [`PMID 19030762`_] * LGR5 is a Wnt target gene in a human colon cancer cell line [`PMID 17934449`_] * Meta-analysis and HuGE review of gene-disease association. (HuGE Navigator) [`PMID 19602701`_] * Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [`PMID 20879858`_] * Loss of LGR5 is associated with colorectal cancer. [`PMID 21829496`_] * Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator) [`PMID 18372903`_] * LGR5 expression can be related to cellular stemness and can be considered as a new phenotypic marker of residual human corneal limbal stem cells. [`PMID 22322201`_] * Lgr5 has been recently identified as a novel stem cell marker of the intestinal epithelium and the hair follicle[REVIEW] [`PMID 19197002`_] * Involvement and overexpression of LGR5, not only in early events but also in late events in colorectal tumorigenesis. [`PMID 20384634`_] * Results point to rare evidence of Lgr5 positive stem cell like cells in the metastatic cascade of colorectal cancer. [`PMID 21577318`_] * Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator) [`PMID 20889853`_] * Observational study of gene-disease association. (HuGE Navigator) [`PMID 20712903`_] * The study suggests a connection between CD133 and EGR1 and emphasises the importance of the EGR1/TCF4/CD133/LGR5 network in colorectal cancer. [`PMID 21436631`_] * LGR4 and LGR5 bind the R-spondins with high affinity and mediate the potentiation of Wnt/beta-catenin signaling by enhancing Wnt-induced LRP6 phosphorylation. [`PMID 21693646`_] * An attenuated mRNA level of the newly identified transcript variant GPR49Delta5 is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. [`PMID 21978106`_] * Observational study and meta-analysis of gene-disease association. (HuGE Navigator) [`PMID 20927120`_] * The results suggest that up-regulation of Lgr5 expression, especially in female patients, may play an important role in colorectal carcinogenesis, probably through the WNT/beta-catenin pathway, but not involve the progression of the colorectal carcinomas. [`PMID 20195621`_] * Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) [`PMID 20571754`_] * gene [coding region] mutations excluded as being involved in the pathogenesis of autosomal-dominant ankyloglossia [`PMID 20042737`_] * GPR49 may have a role in human colon and ovarian primary tum [`PMID 16575208`_] * The stem cell marker LgR5 is expressed in esophageal adenocarcinomas, irrespective of association with Barrett's esophagus, and appears to have negative impact on survival. [`PMID 21345220`_] * High LGR5 is associated with colorectal tumorigenesis. [`PMID 21273608`_] * Gpr49 may be critically involved in the development of hepatocellular carcinoma with beta-catenin mutations [`PMID 12601349`_] * GPR49 is expressed downstream of Hedgehog signaling and promotes cell proliferation and tumor formation in cases of basal cell carcinoma. [`PMID 18688030`_] * LGR5, a stem cell marker, showed an increase in F3-Ngn1, although transient overexpression of Ngn1 did not induce upregulation of LGR5, suggesting that LGR5 is not a direct transcriptional target of Ngn1. [`PMID 19813087`_] .. _PMID 19549212: http://www.ncbi.nlm.nih.gov/pubmed/19549212 .. _PMID 21125339: http://www.ncbi.nlm.nih.gov/pubmed/21125339 .. _PMID 19030762: http://www.ncbi.nlm.nih.gov/pubmed/19030762 .. _PMID 17934449: http://www.ncbi.nlm.nih.gov/pubmed/17934449 .. _PMID 19602701: http://www.ncbi.nlm.nih.gov/pubmed/19602701 .. _PMID 20879858: http://www.ncbi.nlm.nih.gov/pubmed/20879858 .. _PMID 21829496: http://www.ncbi.nlm.nih.gov/pubmed/21829496 .. _PMID 18372903: http://www.ncbi.nlm.nih.gov/pubmed/18372903 .. _PMID 22322201: http://www.ncbi.nlm.nih.gov/pubmed/22322201 .. _PMID 19197002: http://www.ncbi.nlm.nih.gov/pubmed/19197002 .. _PMID 20384634: http://www.ncbi.nlm.nih.gov/pubmed/20384634 .. _PMID 21577318: http://www.ncbi.nlm.nih.gov/pubmed/21577318 .. _PMID 20889853: http://www.ncbi.nlm.nih.gov/pubmed/20889853 .. _PMID 20712903: http://www.ncbi.nlm.nih.gov/pubmed/20712903 .. _PMID 21436631: http://www.ncbi.nlm.nih.gov/pubmed/21436631 .. _PMID 21693646: http://www.ncbi.nlm.nih.gov/pubmed/21693646 .. _PMID 21978106: http://www.ncbi.nlm.nih.gov/pubmed/21978106 .. _PMID 20927120: http://www.ncbi.nlm.nih.gov/pubmed/20927120 .. _PMID 20195621: http://www.ncbi.nlm.nih.gov/pubmed/20195621 .. _PMID 20571754: http://www.ncbi.nlm.nih.gov/pubmed/20571754 .. _PMID 20042737: http://www.ncbi.nlm.nih.gov/pubmed/20042737 .. _PMID 16575208: http://www.ncbi.nlm.nih.gov/pubmed/16575208 .. _PMID 21345220: http://www.ncbi.nlm.nih.gov/pubmed/21345220 .. _PMID 21273608: http://www.ncbi.nlm.nih.gov/pubmed/21273608 .. _PMID 12601349: http://www.ncbi.nlm.nih.gov/pubmed/12601349 .. _PMID 18688030: http://www.ncbi.nlm.nih.gov/pubmed/18688030 .. _PMID 19813087: http://www.ncbi.nlm.nih.gov/pubmed/19813087 .. _LGR5 Pubmed: PubMed Articles *************** *Recent articles:* * Brzeszczynska J et al. "Molecular profile of organ culture-stored corneal epithelium: LGR5 is a potential new phenotypic marker of residual human corneal limbal epithelial stem cells." Int J Mol Med. 2012 May;29(5):871-6. `PMID 22322201`_ * Rot S et al. "A novel splice variant of the stem cell marker LGR5/GPR49 is correlated with the risk of tumor-related death in soft-tissue sarcoma patients." BMC Cancer. 2011 Oct 6;11:429. `PMID 21978106`_ * Walker F et al. "LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines." PLoS One. 2011;6(7):e22733. `PMID 21829496`_ * Carmon KS et al. "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling." Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11452-7. `PMID 21693646`_ * Ernst A et al. "A gene signature distinguishing CD133hi from CD133- colorectal cancer cells: essential role for EGR1 and downstream factors." Pathology. 2011 Apr;43(3):220-7. `PMID 21436631`_ * Kleist B et al. "Expression of the adult intestinal stem cell marker Lgr5 in the metastatic cascade of colorectal cancer." Int J Clin Exp Pathol. 2011 Apr;4(4):327-35. `PMID 21577318`_ * Takahashi H et al. "Significance of Lgr5(+ve) cancer stem cells in the colon and rectum." Ann Surg Oncol. 2011 Apr;18(4):1166-74. `PMID 21125339`_ * von Rahden BH et al. "LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's esophagus?." J Exp Clin Cancer Res. 2011 Feb 23;30:23. `PMID 21345220`_ * Takeda K et al. "Expression of LGR5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis." Anticancer Res. 2011 Jan;31(1):263-70. `PMID 21273608`_ * Zhou DZ et al. "Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese." J Hum Genet. 2010 Dec;55(12):810-5. `PMID 20927120`_ .. _PMID 21436631: http://www.ncbi.nlm.nih.gov/pubmed/21436631 .. _PMID 21693646: http://www.ncbi.nlm.nih.gov/pubmed/21693646 .. _PMID 20927120: http://www.ncbi.nlm.nih.gov/pubmed/20927120 .. _PMID 21577318: http://www.ncbi.nlm.nih.gov/pubmed/21577318 .. _PMID 21978106: http://www.ncbi.nlm.nih.gov/pubmed/21978106 .. _PMID 21345220: http://www.ncbi.nlm.nih.gov/pubmed/21345220 .. _PMID 22322201: http://www.ncbi.nlm.nih.gov/pubmed/22322201 .. _PMID 21273608: http://www.ncbi.nlm.nih.gov/pubmed/21273608 .. _PMID 21125339: http://www.ncbi.nlm.nih.gov/pubmed/21125339 .. _PMID 21829496: http://www.ncbi.nlm.nih.gov/pubmed/21829496 *Top Pubmed articles linked to gene LGR5 matching any search term:* * Hotta K et al. "Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography." J Hum Genet. 2012 May;57(5):305-10. `PMID 22377712`_ * Carpino G et al. "Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages." J Anat. 2012 Feb;220(2):186-99. `PMID 22136171`_ * Cheng I et al. "Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies." Gut. 2011 Dec;60(12):1703-11. `PMID 21602532`_ * Sei Y et al. "A stem cell marker-expressing subset of enteroendocrine cells resides at the crypt base in the small intestine." Am J Physiol Gastrointest Liver Physiol. 2011 Feb;300(2):G345-56. `PMID 21088235`_ * de Miguel-Yanes JM et al. "Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms." Diabetes Care. 2011 Jan;34(1):121-5. `PMID 20889853`_ * Zhou DZ et al. "Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese." J Hum Genet. 2010 Dec;55(12):810-5. `PMID 20927120`_ * Stange DE et al. "Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain." Gut. 2010 Sep;59(9):1236-44. `PMID 20479215`_ * Morgan AR et al. "Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study." BMC Med Genet. 2010 Aug 16;11:125. `PMID 20712903`_ * Voight BF et al. "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis." Nat Genet. 2010 Jul;42(7):579-89. `PMID 20581827`_ * Zhao J et al. "Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI." Diabetes. 2010 Mar;59(3):751-5. `PMID 19933996`_ * Schleinitz D et al. "Lack of significant effects of the type 2 diabetes susceptibility loci JAZF1, CDC123/CAMK1D, NOTCH2, ADAMTS9, THADA, and TSPAN8/LGR5 on diabetes and quantitative metabolic traits." Horm Metab Res. 2010 Jan;42(1):14-22. `PMID 19670153`_ * Simonis-Bik AM et al. "Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function." Diabetes. 2010 Jan;59(1):293-301. `PMID 19833888`_ * Lango Allen H et al. "Polygenic risk variants for type 2 diabetes susceptibility modify age at diagnosis in monogenic HNF1A diabetes." Diabetes. 2010 Jan;59(1):266-71. `PMID 19794065`_ * Hu C et al. "PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population." PLoS One. 2009 Oct 28;4(10):e7643. `PMID 19862325`_ * Meigs JB et al. "Genotype score in addition to common risk factors for prediction of type 2 diabetes." N Engl J Med. 2008 Nov 20;359(21):2208-19. `PMID 19020323`_ * Zeggini E et al. "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes." Nat Genet. 2008 May;40(5):638-45. `PMID 18372903`_ * None et al. "Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls." Nature. 2007 Jun 7;447(7145):661-78. `PMID 17554300`_ * Hsu SY et al. "Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region." Mol Endocrinol. 1998 Dec;12(12):1830-45. `PMID 9849958`_ .. _PMID 20889853: http://www.ncbi.nlm.nih.gov/pubmed/20889853 .. _PMID 20712903: http://www.ncbi.nlm.nih.gov/pubmed/20712903 .. _PMID 20581827: http://www.ncbi.nlm.nih.gov/pubmed/20581827 .. _PMID 20927120: http://www.ncbi.nlm.nih.gov/pubmed/20927120 .. _PMID 22377712: http://www.ncbi.nlm.nih.gov/pubmed/22377712 .. _PMID 19862325: http://www.ncbi.nlm.nih.gov/pubmed/19862325 .. _PMID 18372903: http://www.ncbi.nlm.nih.gov/pubmed/18372903 .. _PMID 17554300: http://www.ncbi.nlm.nih.gov/pubmed/17554300 .. _PMID 9849958: http://www.ncbi.nlm.nih.gov/pubmed/9849958 .. _PMID 19670153: http://www.ncbi.nlm.nih.gov/pubmed/19670153 .. _PMID 19833888: http://www.ncbi.nlm.nih.gov/pubmed/19833888 .. _PMID 19794065: http://www.ncbi.nlm.nih.gov/pubmed/19794065 .. _PMID 19020323: http://www.ncbi.nlm.nih.gov/pubmed/19020323 .. _PMID 21602532: http://www.ncbi.nlm.nih.gov/pubmed/21602532 .. _PMID 21088235: http://www.ncbi.nlm.nih.gov/pubmed/21088235 .. _PMID 22136171: http://www.ncbi.nlm.nih.gov/pubmed/22136171 .. _PMID 19933996: http://www.ncbi.nlm.nih.gov/pubmed/19933996 .. _PMID 20479215: http://www.ncbi.nlm.nih.gov/pubmed/20479215