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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 967 | 1q32.1 | LGR6 | leucine rich repeat containing G protein-coupled receptor 6 | 8 |
| Mouse | 7 | 967 | 1 E4 | Lgr6 | leucine-rich repeat-containing G protein-coupled receptor 6 | |
| Rat | 7 | 965 | 13q13 | Lgr6 | leucine-rich repeat-containing G protein-coupled receptor 6 | |
| Previous and Unofficial Names |
| VTS20631 | leucine-rich repeat-containing G protein-coupled receptor 6 | leucine-rich repeat containing G protein-coupled receptor 6 |
| Database Links |
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| Specialist databases | |
| GPCRdb | lgr6_human (Hs), lgr6_mouse (Mm) |
| Other databases | |
| Alphafold | Q9HBX8 (Hs), Q3UVD5 (Mm) |
| CATH/Gene3D | 3.80.10.10 |
| Ensembl Gene | ENSG00000133067 (Hs), ENSMUSG00000042793 (Mm), ENSRNOG00000005093 (Rn) |
| Entrez Gene | 59352 (Hs), 329252 (Mm), 498233 (Rn) |
| Human Protein Atlas | ENSG00000133067 (Hs) |
| KEGG Gene | hsa:59352 (Hs), mmu:329252 (Mm), rno:498233 (Rn) |
| OMIM | 606653 (Hs) |
| Pharos | Q9HBX8 (Hs) |
| RefSeq Nucleotide | NM_021636 (Hs), NM_001033409 (Mm) |
| RefSeq Protein | NP_067649 (Hs), NP_001028581 (Mm) |
| UniProtKB | Q9HBX8 (Hs), Q3UVD5 (Mm) |
| Wikipedia | LGR6 (Hs) |
| Natural/Endogenous Ligands |
| R-spondin-1 {Sp: Human} |
| R-spondin-2 {Sp: Human} |
| R-spondin-3 {Sp: Human} |
| R-spondin-4 {Sp: Human} |
| R-spondins |
| Comments: Proposed ligands, single publication |
Download all structure-activity data for this target as a CSV file 
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| The four R-spondins can bind to LGR4, LGR5, and LGR6, which specifically associate with Frizzled and LRPs—proteins that are activated by extracellular Wnt molecules- and then trigger canonical Wnt signalling to increase gene expression [5]. LGR6 is not coupled with heterotrimeric G proteins or to β-arrestin following R-spondin activation [6]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immuno Process Associations | ||
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| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Lgr6 is expressed in early hair progenitor cells and becomes restricted to a limited number of cells at the central isthmus [10]. Prenatally, Lgr-6 positive cells established hair follicles, sebaceous glands and an interfollicular epidermis. Postanally, Lgr-6 positive cells established sebaceous glands and an interfollicular epidermis, whereas their contribution to hair lineages slowly decreased with age [10]. In zebrafish, Lgr6 is expressed in the notochord, Kupffer's vesicle, the most anterior region of diencephalon, otic vesicles, and the anterior and posterior lateral line primodia by 24 h post-fertilisation (hpf). From 48 to 72 hpf, Lgr6 expression is restricted to the anterior and posterior neuromasts, otic vesicles, pharyngeal arches, pectoral fin buds, and cranial cartilages such as Meckel's cartilages, ceratohyals, and trabeculae [7]. | ||||||||
| Expression Datasets |
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| Functional Assay Comments |
| Stimulation of LGR6 with R-spondin 1-3 enhances Wnt/β-catenin signalling [6]. |
| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology Comments |
| LGR6 mutations have been detected in colon cancer, pancreatic cancer and ovarian cancer [6]. LGR6 is hypermethylated in up to 50% of colon cancer samples. LGR6 truncation mutant has been identified in ovarian cancer. These data imply that LGR6 may act as tumour suppressor for colon and ovarian cancer [6]. |
| Biologically Significant Variants
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| Biologically Significant Variant Comments | ||||||||||||||||||
| Variant numbering based on RefSeq Protein NP_067649 |
| General Comments |
| LGR6 is a member of type B leucine-rich repeat containing G protein-coupled receptor [7]. LGR6 was shown to mark a population of multipotent stem cells in mouse skin that can give rise to all lineages of skin; however LGR6-knockout mice are healthy and fertile [10]. |
1. Amoh Y, Aki R, Hamada Y, Niiyama S, Eshima K, Kawahara K, Sato Y, Tani Y, Hoffman RM, Katsuoka K. (2012) Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury. J Dermatol, 39 (1): 33-8. [PMID:22098554]
2. Barker N, Clevers H. (2010) Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology, 138 (5): 1681-96. [PMID:20417836]
3. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. (2011) R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci USA, 108 (28): 11452-7. [PMID:21693646]
4. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C et al.. (2003) The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res, 13 (10): 2265-70. [PMID:12975309]
5. de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M et al.. (2011) Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature, 476 (7360): 293-7. [PMID:21727895]
6. Gong X, Carmon KS, Lin Q, Thomas A, Yi J, Liu Q. (2012) LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PLoS ONE, 7 (5): e37137. [PMID:22615920]
7. Hirose K, Shimoda N, Kikuchi Y. (2011) Expression patterns of lgr4 and lgr6 during zebrafish development. Gene Expr Patterns, 11 (7): 378-83. [PMID:21570488]
8. Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ. (2000) The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Mol Endocrinol, 14 (8): 1257-71. [PMID:10935549]
9. Nath M, Offers M, Hummel M, Seissler J. (2011) Isolation and in vitro expansion of Lgr6-positive multipotent hair follicle stem cells. Cell Tissue Res, 344 (3): 435-44. [PMID:21484413]
10. Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, van de Wetering M, van den Born M, Begthel H, Vries RG, Stange DE, Toftgård R, Clevers H. (2010) Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science, 327 (5971): 1385-9. [PMID:20223988]
