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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 | 617 | Xq28 | GPR50 | G protein-coupled receptor 50 | 10 |
Mouse | 7 | 591 | X 36.98 cM | Gpr50 | G-protein-coupled receptor 50 | 10 |
Rat | 3 | 119 | 17p12 | Gpr50 | G protein-coupled receptor 50 |
Previous and Unofficial Names ![]() |
MTNRL | H9 | Mel1c | melatonin-related receptor |
Database Links ![]() |
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Specialist databases | |
GPCRdb | mtr1l_human (Hs), mtr1l_mouse (Mm) |
Other databases | |
Alphafold | Q13585 (Hs), O88495 (Mm), Q62953 (Rn) |
ChEMBL Target | CHEMBL3341577 (Hs) |
Ensembl Gene | ENSG00000102195 (Hs), ENSMUSG00000056380 (Mm), ENSRNOG00000011335 (Rn) |
Entrez Gene | 9248 (Hs), 14765 (Mm), 117097 (Rn) |
Human Protein Atlas | ENSG00000102195 (Hs) |
KEGG Gene | hsa:9248 (Hs), mmu:14765 (Mm), rno:117097 (Rn) |
OMIM | 309200 (Hs), 300207 (Hs) |
Pharos | Q13585 (Hs) |
RefSeq Nucleotide | NM_004224 (Hs), NM_010340 (Mm), NM_001191915 (Rn) |
RefSeq Protein | NP_004215 (Hs), NP_034470 (Mm), NP_001178844 (Rn) |
UniProtKB | Q13585 (Hs), O88495 (Mm), Q62953 (Rn) |
Wikipedia | GPR50 (Hs) |
Tissue Distribution ![]() |
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Tissue Distribution Comments | ||||||||
In situ hybridisation revealed restricted expression of GPR50 in the ependymal layer, extending from caudal hypothalamic sections through to the beginning of the retrochiasmatic nucleus. Photoperiodic regulation of GPR50 is observed in tanycytes of the ependymal layer [2]. Polyclonal antibodies are now available for detection of human GPR50, which map to different epitopes corresponding to the N-terminus, C-terminus and two additional regions within the intracellular tail. Antibodies are sufficiently sufficient to detect GPR50 in rat pituitary and human hippocampus [11]. |
Expression Datasets ![]() |
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Functional Assays ![]() |
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Physiological Functions Comments | |
Physiological function of GPR50 remains unclear, although studies implicate the receptor in energy homeostasis [12]. |
Physiological Consequences of Altering Gene Expression ![]() |
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Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology ![]() |
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Clinically-Relevant Mutations and Pathophysiology Comments | ||||||||||||||||||||||||||||
There is an association between the 502-505 deletion polymorphism and age of onset of bipolar disorder (p = 0.049), number of episodes (p = 0.044), hypomanic symptoms (p = 0.019), and initial thinking time (p = 0.027), in women; and in family history of depression in men [18]. No significant association was found between GPR50 human missense polymorphism I606V and adolescent idiopathic scoliosis [21]. GPR50(Δ502-505), or a variant in tight linkage disequilibrium with this polymorphism, may be a sex-specific risk factor for susceptibility to bipolar disorder, and other variants in the gene may be sex-specific risk factors in the development of schizophrenia [24]. This finding was not replicated in a second study in a Northern Swedish population [1]. Additionally no association was seen between haplotypes or SNPs of GPR50 and childhood-onset mood disorders [7]. Significant association between Autistic Spectrum Disorder and two in GPR50, Δ502-505 and T532A, has been shown, but this does not stand up to post-hoc testing. A second study found no variants linked to ASD [6], [14]. Carriers of two copies of the mutant allele at C-16X2GPR50T, Ins501Del, and A1582G had significantly higher fasting circulating triglyceride levels, replicated in two sets of 500 and 585 subjects. C-16X2GPR50T carriers were also shown to have significantly lower circulating HDL-cholesterol levels than wild-type subjects [5]. Seasonal Affective Disorder has been associated with a GPR50 SNP (intronic rs2072621) in females [4]. |
Biologically Significant Variants ![]() |
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General Comments |
GPR50 (melatonin-related receptor) is structurally related to the melatonin receptors, MT1 and MT2, but does not bind melatonin, and its endogenous ligand has not been identified. GPR50 heterodimerises constitutively and specifically with MT1 to abolish high-affinity agonist binding and G protein coupling. Although GPR50 also heterodimerizes with MT2, this had no effect on function in intact cells [16]. |
1. Alaerts M, Venken T, Lenaerts AS, De Zutter S, Norrback KF, Adolfsson R, Del-Favero J. (2006) Lack of association of an insertion/deletion polymorphism in the G protein-coupled receptor 50 with bipolar disorder in a Northern Swedish population. Psychiatr Genet, 16 (6): 235-6. [PMID:17106423]
2. Barrett P, Ivanova E, Graham ES, Ross AW, Wilson D, Plé H, Mercer JG, Ebling FJ, Schuhler S, Dupré SM, Loudon A, Morgan PJ. (2006) Photoperiodic regulation of cellular retinol binding protein, CRBP1 [corrected] and nestin in tanycytes of the third ventricle ependymal layer of the Siberian hamster. J Endocrinol, 191 (3): 687-98. [PMID:17170225]
3. Batailler M, Mullier A, Sidibe A, Delagrange P, Prévot V, Jockers R, Migaud M. (2012) Neuroanatomical distribution of the orphan GPR50 receptor in adult sheep and rodent brains. J Neuroendocrinol, 24 (5): 798-808. [PMID:22512326]
4. Bechtold DA, Sidibe A, Saer BR, Li J, Hand LE, Ivanova EA, Darras VM, Dam J, Jockers R, Luckman SM et al.. (2012) A role for the melatonin-related receptor GPR50 in leptin signaling, adaptive thermogenesis, and torpor. Curr Biol, 22 (1): 70-7. [PMID:22197240]
5. Bhattacharyya S, Luan J, Challis B, Keogh J, Montague C, Brennand J, Morten J, Lowenbeim S, Jenkins S, Farooqi IS, Wareham NJ, O'Rahilly S. (2006) Sequence variants in the melatonin-related receptor gene (GPR50) associate with circulating triglyceride and HDL levels. J Lipid Res, 47 (4): 761-6. [PMID:16436372]
6. Chaste P, Clement N, Mercati O, Guillaume JL, Delorme R, Botros HG, Pagan C, Périvier S, Scheid I, Nygren G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg C, Serrano E, Lemière N, Launay JM, Mouren-Simeoni MC, Leboyer M, Gillberg C, Jockers R, Bourgeron T. (2010) Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population. PLoS ONE, 5 (7): e11495. [PMID:20657642]
7. Feng Y, Wigg K, King N, Vetró A, Kiss E, Kapornai K, Mayer L, Gádoros J, Kennedy JL, Kovacs M, Barr CL, International Consortium for Childhood-Onset Mood Disorders. (2007) GPR50 is not associated with childhood-onset mood disorders in a large sample of Hungarian families. Psychiatr Genet, 17 (6): 347-50. [PMID:18075476]
8. Gerwins P, Nordstedt C, Fredholm BB. (1990) Characterization of adenosine A1 receptors in intact DDT1 MF-2 smooth muscle cells. Mol Pharmacol, 38 (5): 660-6. [PMID:2172773]
9. Grünewald E, Kinnell HL, Porteous DJ, Thomson PA. (2009) GPR50 interacts with neuronal NOGO-A and affects neurite outgrowth. Mol Cell Neurosci, 42 (4): 363-71. [PMID:19699797]
10. Gubitz AK, Reppert SM. (1999) Assignment of the melatonin-related receptor to human chromosome X (GPR50) and mouse chromosome X (Gpr50). Genomics, 55 (2): 248-51. [PMID:9933574]
11. Hamouda HO, Chen P, Levoye A, Sözer-Topçular N, Daulat AM, Guillaume JL, Ravid R, Savaskan E, Ferry G, Boutin JA, Delagrange P, Jockers R, Maurice P. (2007) Detection of the human GPR50 orphan seven transmembrane protein by polyclonal antibodies mapping different epitopes. J Pineal Res, 43 (1): 10-5. [PMID:17614830]
12. Ivanova EA, Bechtold DA, Dupré SM, Brennand J, Barrett P, Luckman SM, Loudon AS. (2008) Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse. Am J Physiol Endocrinol Metab, 294 (1): E176-82. [PMID:17957037]
13. Jockers R, Maurice P, Boutin JA, Delagrange P. (2008) Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?. Br J Pharmacol, 154 (6): 1182-95. [PMID:18493248]
14. Jonsson L, Ljunggren E, Bremer A, Pedersen C, Landén M, Thuresson K, Giacobini M, Melke J. (2010) Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC Med Genomics, 3: 10. [PMID:20377855]
15. Lee S, Bookout AL, Lee CE, Gautron L, Harper MJ, Elias CF, Lowell BB, Elmquist JK. (2012) Laser-capture microdissection and transcriptional profiling of the dorsomedial nucleus of the hypothalamus. J Comp Neurol, 520 (16): 3617-32. [PMID:22473294]
16. Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P, Jockers R. (2006) The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. EMBO J, 25 (13): 3012-23. [PMID:16778767]
17. Li J, Hand LE, Meng QJ, Loudon AS, Bechtold DA. (2011) GPR50 interacts with TIP60 to modulate glucocorticoid receptor signalling. PLoS ONE, 6 (8): e23725. [PMID:21858214]
18. Macintyre DJ, McGhee KA, Maclean AW, Afzal M, Briffa K, Henry B, Thomson PA, Muir WJ, Blackwood DH. (2010) Association of GPR50, an X-linked orphan G protein-coupled receptor, and affective disorder in an independent sample of the Scottish population. Neurosci Lett, 475 (3): 169-73. [PMID:20371266]
19. McCormick MB, Coulombe PA, Fuchs E. (1991) Sorting out IF networks: consequences of domain swapping on IF recognition and assembly. J Cell Biol, 113 (5): 1111-24. [PMID:1710225]
20. Reppert SM, Weaver DR, Godson C. (1996) Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol Sci, 17 (3): 100-2. [PMID:8936344]
21. Shyy W, Wang K, Gurnett CA, Dobbs MB, Miller NH, Wise C, Sheffield VC, Morcuende JA. (2010) Evaluation of GPR50, hMel-1B, and ROR-alpha melatonin-related receptors and the etiology of adolescent idiopathic scoliosis. J Pediatr Orthop, 30 (6): 539-43. [PMID:20733416]
22. Sidibe A, Mullier A, Chen P, Baroncini M, Boutin JA, Delagrange P, Prevot V, Jockers R. (2010) Expression of the orphan GPR50 protein in rodent and human dorsomedial hypothalamus, tanycytes and median eminence. J Pineal Res, 48 (3): 263-9. [PMID:20210849]
23. Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J. (2003) Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol, 196 (1): 144-53. [PMID:12767050]
24. Thomson PA, Wray NR, Thomson AM, Dunbar DR, Grassie MA, Condie A, Walker MT, Smith DJ, Pulford DJ, Muir W, Blackwood DH, Porteous DJ. (2005) Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor. Mol Psychiatry, 10 (5): 470-8. [PMID:15452587]
25. Zhang JC, Xie YF, Liu SJ, Dai LB, Li JP. (2010) [The expression of melatonin receptor in human hypertrophic scar]. Zhonghua Zheng Xing Wai Ke Za Zhi, 26 (3): 203-7. [PMID:20737950]