LGR5

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

NCBI Summary

None available.

OMIM

OMIM ID:`OMIM ID 606667 `_

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.

Gene Ontology

• G-protein coupled receptor signaling pathway
• protein-hormone receptor activity
• G-protein coupled receptor activity
• inner ear development
• integral to plasma membrane

KEGG Pathways

• Neuroactive ligand-receptor interaction

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]

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

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