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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83. 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]

84. 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]

85. 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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87. 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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89. Marazziti D, Mandillo S, Di Pietro C, Golini E, Matteoni R, Tocchini-Valentini GP. (2007) GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. Proc. Natl. Acad. Sci. U.S.A., 104 (23): 9846-51. [PMID:17519329]

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93. 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]

94. 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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96. 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]

97. 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]

98. 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]

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100. 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]

101. 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]

102. 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]

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104. 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]

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106. 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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109. 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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119. 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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129. 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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132. 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]

133. 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]

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135. 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]

136. 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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146. 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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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 Immunotherapeutics University of Cambridge Level 6, Addenbrooke's Centre for Clinical Investigation (ACCI) Box 110, Addenbrooke's Hospital Cambridge, CB2 0QQ UK Satoru Eguchi Cardiovascular Research Center Temple University School of Medicine 3500 N Broad Street Philadelphia PA 19140 USA Anthony Harmar (1951-2014) formerly of the University of Edinburgh, Edinburgh, Scotland Nick Holliday Room CS6 The Medical School, Floor C Queen's Medical Centre Nottingham NG7 2UH UK 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 Leigh Stoddart Division of Biochemistry and Molecular Biology Institute of Biomedical and Life Sciences University of Glasgow Glasgow G12 8QQ UK Laura Storjohann (GPR39) Salt Lake City UT 84124 Walter (Wally) Thomas School of Biomedical Sciences The University of Queensland BNE, QUEENSLAND 4072 Australia Kalyan Tirupula (MAS1) Department of Molecular Cardiology Lerner Research Institute The Cleveland Clinic Foundation 9500 Euclid Ave. Cleveland, OH 44195 USA Patrick Vanderheyden Department of Molecular and Biochemical Pharmacology Vrije Universiteit Brussel Pleinlaan 2 1050, Brussels Belgium