Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [29], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [20]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.

Table 1: Class A orphan GPCRs with putative endogenous ligands

GPR1	GPR3	GPR4	GPR6	GPR12	GPR15	GPR17	GPR20
GPR22	GPR26	GPR31	GPR34	GPR35	GPR37	GPR39	GPR50
GPR63	GRP65	GPR68	GPR75	GPR84	GPR87	GPR88	GPR132
GPR149	GPR161	GPR183	LGR4	LGR5	LGR6	MAS1	MRGPRD
MRGPRX1	MRGPRX2	P2RY10	TAAR2

In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119).

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84. Luo J, Zhou W, Zhou X, Li D, Weng J, Yi Z, Cho SG, Li C, Yi T, Wu X, Li XY, de Crombrugghe B, Höök M, Liu M. (2009) Regulation of bone formation and remodeling by G-protein-coupled receptor 48. Development, 136 (16): 2747-56. [PMID:19605502]

85. Maekawa A, Balestrieri B, Austen KF, Kanaoka Y. (2009) GPR17 is a negative regulator of the cysteinyl leukotriene 1 receptor response to leukotriene D4. Proc. Natl. Acad. Sci. U.S.A., 106 (28): 11685-90. [PMID:19561298]

86. Mantey SA, Coy DH, Entsuah LK, Jensen RT. (2004) Development of Bombesin Analogues With Conformationally-Restricted Amino Acid Substitutions With Enhanced Selectivity for the Orphan Receptor, hBRS-3. J Pharmacol Exp Ther., 310: 1161-1170. [PMID:15102928]

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88. Marazziti D, Di Pietro C, Golini E, Mandillo S, Matteoni R, Tocchini-Valentini GP. (2009) Macroautophagy of the GPR37 orphan receptor and Parkinson disease-associated neurodegeneration. Autophagy, 5 (5): 741-2. [PMID:19398891]

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94. Meyer RC, Giddens MM, Schaefer SA, Hall RA. (2013) GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. Proc. Natl. Acad. Sci. U.S.A., 110 (23): 9529-34. [PMID:23690594]

95. Moody TW, Mantey SA, Moreno P, Nakamura T, Lacivita E, Leopoldo M, Jensen RT. (2015) ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth. Peptides, 64: 55-61. [PMID:25554218]

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97. Murakami M, Shiraishi A, Tabata K, Fujita N. (2008) Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun., 371 (4): 707-12. [PMID:18466763]

98. Müller A, Kleinau G, Piechowski CL, Müller TD, Finan B, Pratzka J, Grüters A, Krude H, Tschöp M, Biebermann H. (2013) G-protein coupled receptor 83 (GPR83) signaling determined by constitutive and zinc(II)-induced activity. PLoS ONE, 8 (1): e53347. [PMID:23335960]

99. Müller A, Leinweber B, Fischer J, Müller TD, Grüters A, Tschöp MH, Knäuper V, Biebermann H, Kleinau G. (2014) The extracellular N-terminal domain of G-protein coupled receptor 83 regulates signaling properties and is an intramolecular inverse agonist. BMC Res Notes, 7: 913. [PMID:25516095]

100. Nambu H, Fukushima M, Hikichi H, Inoue T, Nagano N, Tahara Y, Nambu T, Ito J, Ogawa Y, Ozaki S et al.. (2011) Characterization of metabolic phenotypes of mice lacking GPR61, an orphan G-protein coupled receptor. Life Sci., 89 (21-22): 765-72. [PMID:21971119]

101. Niedernberg A, Tunaru S, Blaukat A, Ardati A, Kostenis E. (2003) Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63. Cell Signal, 15: 435-446. [PMID:12618218]

102. Nikaido Y, Koyama Y, Yoshikawa Y, Furuya T, Takeda S. (2015) Mutation analysis and molecular modeling for the investigation of ligand-binding modes of GPR84. J. Biochem., 157 (5): 311-20. [PMID:25425658]

103. Ning Y, O'Neill K, Lan H, Pang L, Shan LX, Hawes BE, Hedrick JA. (2008) Endogenous and synthetic agonists of GPR119 differ in signalling pathways and their effects on insulin secretion in MIN6c4 insulinoma cells. Br. J. Pharmacol., 155 (7): 1056-65. [PMID:18724386]

104. No authors listed. (2005) Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. (Retraction). J. Biol. Chem., 280 (52): 43280. [PMID:16498716]

105. Oka S, Nakajima K, Yamashita A, Kishimoto S, Suqiura T. (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun, 362 (4): 928-934. [PMID:17765871]

106. Oka S, Ota R, Shima M, Yamashita A, Sugiura T. (2010) GPR35 is a novel lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun., 395 (2): 232-7. [PMID:20361937]

107. Oka S, Toshida T, Maruyama K, Nakajima K, Yamashita A, Sugiura T. (2009) 2-Arachidonoyl-sn-glycero-3-phosphoinositol: A Possible Natural Ligand for GPR55. J Biochem, 145 (1): 13-20. [PMID:18845565]

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110. Padmanabhan S, Myers AG, Prasad BM. (2009) Constitutively active GPR6 is located in the intracellular compartments. FEBS Lett., 583 (1): 107-12. [PMID:19059244]

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116. Rezgaoui M, Süsens U, Ignatov A, Gelderblom M, Glassmeier G, Franke I, Urny J, Imai Y, Takahashi R, Schaller HC. (2006) The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37. J Cell Sci, 119: 542-549. [PMID:16443751]

117. Robas N, Mead E, Fidock M. (2003) MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J Biol Chem, 278: 44400-44404. [PMID:12915402]

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120. Russell JL, Goetsch SC, Aguilar HR, Coe H, Luo X, Liu N, van Rooij E, Frantz DE, Schneider JW. (2012) Regulated expression of pH sensing G Protein-coupled receptor-68 identified through chemical biology defines a new drug target for ischemic heart disease. ACS Chem. Biol., 7 (6): 1077-83. [PMID:22462679]

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128. Sikand P, Dong X, LaMotte RH. (2011) BAM8-22 peptide produces itch and nociceptive sensations in humans independent of histamine release. J. Neurosci., 31 (20): 7563-7. [PMID:21593341]

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130. Song H, Luo J, Luo W, Weng J, Wang Z, Li B, Li D, Liu M. (2008) Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs definitive erythropoiesis at midgestation through down-regulation of the ATF4 signaling pathway. J. Biol. Chem., 283 (52): 36687-97. [PMID:18955481]

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133. Suzuki M, Takaishi S, Nagasaki M, Onozawa Y, Iino I, Maeda H, Komai T, Oda T. (2013) Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor. J. Biol. Chem., 288 (15): 10684-91. [PMID:23449982]

134. Tabata K, Baba K, Shiraishi A, Ito M, Fujita N. (2007) The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun., 363 (3): 861-6. [PMID:17905198]

135. Takeda S, Okada T, Okamura M, Haga T, Isoyama-Tanaka J, Kuwahara H, Minamino N. (2004) The receptor-Galpha fusion protein as a tool for ligand screening: a model study using a nociceptin receptor-Galphai2 fusion protein. J. Biochem., 135 (5): 597-604. [PMID:15173198]

136. Taniguchi Y, Tonai-Kachi H, Shinjo K. (2006) Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35. FEBS Lett., 580 (21): 5003-8. [PMID:16934253]

137. Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, Horré K, Vanbrabant M, Coun F, Baekelandt V, Delacourte A, Fischer DF, Pollet D, De Strooper B, Merchiers P. (2009) The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science, 323: 946-951. [PMID:19213921]

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139. Toda N, Hao X, Ogawa Y, Oda K, Yu M, Fu Z, Chen Y, Kim Y, Lizarzaburu M, Lively S et al.. (2013) Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes. ACS Med Chem Lett, 4 (8): 790-4. [PMID:24900747]

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147. Weng J, Luo J, Cheng X, Jin C, Zhou X, Qu J, Tu L, Ai D, Li D, Wang J, Martin JF, Amendt BA, Liu M. (2008) Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2. Proc. Natl. Acad. Sci. U.S.A., 105 (16): 6081-6. [PMID:18424556]

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152. Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M. (2007) Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. Biochem Biophys Res Commun, 354: 154-159. [PMID:17214962]

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Stephen P.H. Alexander Associate Professor in Molecular Pharmacology Life Sciences E Floor University of Nottingham Medical School Nottingham NG7 2UH England Jim Battey (BB3) National Institute on Deafness and Other Communication Disorders Building 31 Room 3C02 NIH Bethesda MD 20892 USA Helen E. Benson (Past curator) Centre for Discovery Brain Sciences Edinburgh Medical School: Biomedical Sciences Room 338 Hugh Robson Building George Square Edinburgh EH8 9XD UK Richard V. Benya (BB3) University of Illinois Section of Digestive Diseases and Nutrition 840 South Wood Street (M/C 716) Chicago Illinois 60612 USA Tom I. Bonner Special Volunteer Office of Science Director NIMH Bethesda MD USA Anthony P. Davenport Experimental Medicine and Immunoptherapeutics University of Cambridge Level 6, Addenbrooke's Centre for Clinical Investigation (ACCI) Box 110, Addenbrooke's Hospital Cambridge, CB2 0QQ UK Anthony Harmar (1951-2014) formerly of the University of Edinburgh, Edinburgh, Scotland Robert T. Jensen (BB3) National Institute of Diabetes & Kidney Diseases National Institutes of Health Building 10 Room 9C-103 NIH Bethesda MD 20892 USA Sadashiva Karnik (MAS1) Department of Molecular Cardiology Lerner Research Institute The Cleveland Clinic Foundation 9500 Euclid Ave. Cleveland, OH 44195 USA Evi Kostenis (GPR17) Section Molecular, Cellular and Pharmacobiology Institute for Pharmaceutical Biology University of Bonn Nussallee 6 53115 Bonn Germany Wen Chiy Liew (Past curator) Amy E. Monaghan (Past curator) Chido Mpamhanga (Past curator) Richard Neubig Michigan State University 1355 Bogue St B440 Life Sciences Building East Lansing MI 48824 Adam J. Pawson (Senior curator) Centre for Discovery Brain Sciences Edinburgh Medical School: Biomedical Sciences Room 338 Hugh Robson Building George Square Edinburgh EH8 9XD Jean-Philippe Pin Institut de Génomique Fonctionnelle UMR 5203 CNRS – U 1191 INSERM – Univ. Montpellier 141 rue de la cardonille 34094 Montpellier Cedex 05 - France Joanna L. Sharman (Past senior developer) Centre for Discovery Brain Sciences Edinburgh Medical School: Biomedical Sciences Room 338 Hugh Robson Building George Square Edinburgh EH8 9XD UK Michael Spedding Spedding Research Solutions SARL 6 Rue Ampere Le Vesinet 78110 France Eliot Spindel (BB3) Oregon National Primate Research Center Division of Neuroscience 3181 SW Sam Jackson Park Road Portland OR 97239 USA Laura Storjohann (GPR39) Salt Lake City UT 84124 Kalyan Tirupula (MAS1) Department of Molecular Cardiology Lerner Research Institute The Cleveland Clinic Foundation 9500 Euclid Ave. Cleveland, OH 44195 USA