Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [26], 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 [17]. 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

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).

* Key recommended reading is highlighted with an asterisk

* Akbari P, Gilani A, Sosina O, Kosmicki JA, Khrimian L, Fang YY, Persaud T, Garcia V, Sun D, Li A et al.. (2021) Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity. Science, 373 (6550). DOI: 10.1126/science.abf8683 [PMID:34210852]

* McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, Dong X. (2015) Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature, 519 (7542): 237-41. [PMID:25517090]

* Wirthgen E, Hoeflich A, Rebl A, Günther J. (2017) Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions. Front Immunol, 8: 1957. [PMID:29379504]

Zhang LY, Jia MR, Sun T. (2018) The roles of special proresolving mediators in pain relief. Rev Neurosci, 29 (6): 645-660. [PMID:29420307]

1. Adams JW, Wang J, Davis JR, Liaw C, Gaidarov I, Gatlin J, Dalton ND, Gu Y, Ross J, Behan D, Chien K, Connolly D. (2008) Myocardial expression, signaling, and function of GPR22: a protective role for an orphan G protein-coupled receptor. Am J Physiol Heart Circ Physiol, 295 (2): H509-21. [PMID:18539757]

2. 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]

3. Benned-Jensen T, Rosenkilde MM. (2010) Distinct expression and ligand-binding profiles of two constitutively active GPR17 splice variants. Br J Pharmacol, 159 (5): 1092-105. [PMID:20148890]

4. Bi Y, Dzierba CD, Fink C, Garcia Y, Green M, Han J, Kwon S, Kumi G, Liang Z, Liu Y et al.. (2015) The discovery of potent agonists for GPR88, an orphan GPCR, for the potential treatment of CNS disorders. Bioorg Med Chem Lett, 25 (7): 1443-7. [PMID:25754495]

5. Bjursell M, Gerdin AK, Jönsson M, Surve VV, Svensson L, Huang XF, Törnell J, Bohlooly-Y M. (2006) G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice. Biochem Biophys Res Commun, 348 (2): 359-66. [PMID:16887097]

6. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S et al.. (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA, 98 (16): 8966-71. [PMID:11459929]

7. Brennan, Thomas et al.. (2007) Transgenic mice containing GPCR5-1 gene disruptions. Patent number: US2007/0074299. Assignee: Deltagen. Priority date: 28/08/1999. Publication date: 29/03/2007.

8. Brézillon S, Detheux M, Parmentier M, Hökfelt T, Hurd YL. (2001) Distribution of an orphan G-protein coupled receptor (JP05) mRNA in the human brain. Brain Res, 921 (1-2): 21-30. [PMID:11720708]

9. Bäck M, Powell WS, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE. (2014) Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7. Br J Pharmacol, 171 (15): 3551-74. [PMID:24588652]

10. 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]

11. Catalán V, Gómez-Ambrosi J, Rotellar F, Silva C, Gil MJ, Rodríguez A, Cienfuegos JA, Salvador J, Frühbeck G. (2007) The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus. Clin Endocrinol (Oxf), 66 (4): 598-601. [PMID:17371481]

12. Cavanaugh DJ, Lee H, Lo L, Shields SD, Zylka MJ, Basbaum AI, Anderson DJ. (2009) Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc Natl Acad Sci USA, 106 (22): 9075-80. [PMID:19451647]

13. Chen H, Ikeda SR. (2004) Modulation of ion channels and synaptic transmission by a human sensory neuron-specific G-protein-coupled receptor, SNSR4/mrgX1, heterologously expressed in cultured rat neurons. J Neurosci, 24 (21): 5044-53. [PMID:15163697]

14. Chen Q, Kogan JH, Gross AK, Zhou Y, Walton NM, Shin R, Heusner CL, Miyake S, Tajinda K, Tamura K et al.. (2012) SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory. Eur J Neurosci, 36 (5): 2597-608. [PMID:22697179]

15. Chiang N, Fredman G, Bäckhed F, Oh SF, Vickery T, Schmidt BA, Serhan CN. (2012) Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature, 484 (7395): 524-8. [PMID:22538616]

16. Ciana P, Fumagalli M, Trincavelli ML, Verderio C, Rosa P, Lecca D, Ferrario S, Parravicini C, Capra V, Gelosa P, Guerrini U, Belcredito S, Cimino M, Sironi L, Tremoli E, Rovati GE, Martini C, Abbracchio MP. (2006) The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J, 25 (19): 4615-27. [PMID:16990797]

17. Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR et al.. (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev, 65 (3): 967-86. [PMID:23686350]

18. 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]

19. Dinter J, Mühlhaus J, Wienchol CL, Yi CX, Nürnberg D, Morin S, Grüters A, Köhrle J, Schöneberg T, Tschöp M et al.. (2015) Inverse agonistic action of 3-iodothyronamine at the human trace amine-associated receptor 5. PLoS ONE, 10 (2): e0117774. [PMID:25706283]

20. Divorty N, Mackenzie AE, Nicklin SA, Milligan G. (2015) G protein-coupled receptor 35: an emerging target in inflammatory and cardiovascular disease. Front Pharmacol, 6: 41. [PMID:25805994]

21. Edinger AL, Mankowski JL, Doranz BJ, Margulies BJ, Lee B, Rucker J, Sharron M, Hoffman TL, Berson JF, Zink MC, Hirsch VM, Clements JE, Doms RW. (1997) CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc Natl Acad Sci USA, 94 (26): 14742-7. [PMID:9405683]

22. Edson MA, Lin YN, Matzuk MM. (2010) Deletion of the novel oocyte-enriched gene, Gpr149, leads to increased fertility in mice. Endocrinology, 151 (1): 358-68. [PMID:19887567]

23. Eggerickx D, Denef JF, Labbe O, Hayashi Y, Refetoff S, Vassart G, Parmentier M, Libert F. (1995) Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase. Biochem J, 309 ( Pt 3): 837-43. [PMID:7639700]

24. Engel KM, Schröck K, Teupser D, Holdt LM, Tönjes A, Kern M, Dietrich K, Kovacs P, Krügel U, Scheidt HA et al.. (2011) Reduced food intake and body weight in mice deficient for the G protein-coupled receptor GPR82. PLoS ONE, 6 (12): e29400. [PMID:22216272]

25. Evangelou E, Valdes AM, Kerkhof HJ, Styrkarsdottir U, Zhu Y, Meulenbelt I, Lories RJ, Karassa FB, Tylzanowski P, Bos SD et al.. (2011) Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Ann Rheum Dis, 70 (2): 349-55. [PMID:21068099]

26. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57 (2): 279-88. [PMID:15914470]

27. Gembardt F, Grajewski S, Vahl M, Schultheiss HP, Walther T. (2008) Angiotensin metabolites can stimulate receptors of the Mas-related genes family. Mol Cell Biochem, 319 (1-2): 115-23. [PMID:18636314]

28. Gironacci MM, Adamo HP, Corradi G, Santos RA, Ortiz P, Carretero OA. (2011) Angiotensin (1-7) induces MAS receptor internalization. Hypertension, 58 (2): 176-81. [PMID:21670420]

29. Gomes I, Aryal DK, Wardman JH, Gupta A, Gagnidze K, Rodriguiz RM, Kumar S, Wetsel WC, Pintar JE, Fricker LD et al.. (2013) GPR171 is a hypothalamic G protein-coupled receptor for BigLEN, a neuropeptide involved in feeding. Proc Natl Acad Sci USA, 110 (40): 16211-6. [PMID:24043826]

30. Gomes I, Bobeck EN, Margolis EB, Gupta A, Sierra S, Fakira AK, Fujita W, Müller TD, Müller A, Tschöp MH et al.. (2016) Identification of GPR83 as the receptor for the neuroendocrine peptide PEN. Sci Signal, 9 (425): ra43. [PMID:27117253]

31. Guo Y, Zhang W, Giroux C, Cai Y, Ekambaram P, Dilly AK, Hsu A, Zhou S, Maddipati KR, Liu J et al.. (2011) Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid. J Biol Chem, 286 (39): 33832-40. [PMID:21712392]

32. Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, Guerini D, Baumgarten BU, Roggo S, Wen B et al.. (2011) Oxysterols direct immune cell migration via EBI2. Nature, 475 (7357): 524-7. [PMID:21796212]

33. Hansen W, Westendorf AM, Toepfer T, Mauel S, Geffers R, Gruber AD, Buer J. (2010) Inflammation in vivo is modulated by GPR83 isoform-4 but not GPR83 isoform-1 expression in regulatory T cells. Genes Immun, 11 (4): 357-61. [PMID:20200545]

34. Hase M, Yokomizo T, Shimizu T, Nakamura M. (2008) Characterization of an orphan G protein-coupled receptor, GPR20, that constitutively activates Gi proteins. J Biol Chem, 283 (19): 12747-55. [PMID:18347022]

35. Hay DL, Walker CS, Poyner DR. (2011) Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges. Endocr Relat Cancer, 18 (1): C1-14. [PMID:21051558]

36. Holst B, Egerod KL, Schild E, Vickers SP, Cheetham S, Gerlach LO, Storjohann L, Stidsen CE, Jones R, Beck-Sickinger AG, Schwartz TW. (2007) GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology, 148: 13-20. [PMID:16959833]

37. Huang XP, Karpiak J, Kroeze WK, Zhu H, Chen X, Moy SS, Saddoris KA, Nikolova VD, Farrell MS, Wang S et al.. (2015) Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. Nature, 527 (7579): 477-83. [PMID:26550826]

38. Ignatov A, Hermans-Borgmeyer I, Schaller HC. (2004) Cloning and characterization of a novel G-protein-coupled receptor with homology to galanin receptors. Neuropharmacology, 46 (8): 1114-20. [PMID:15111018]

39. Ignatov A, Lintzel J, Hermans-Borgmeyer I, Kreienkamp HJ, Joost P, Thomsen S, Methner A, Schaller HC. (2003) Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development. J Neurosci, 23 (3): 907-14. [PMID:12574419]

40. Ignatov A, Lintzel J, Kreienkamp HJ, Schaller HC. (2003) Sphingosine-1-phosphate is a high-affinity ligand for the G protein-coupled receptor GPR6 from mouse and induces intracellular Ca2+ release by activating the sphingosine-kinase pathway. Biochem Biophys Res Commun, 311 (2): 329-36. [PMID:14592418]

41. Ignatov A, Robert J, Gregory-Evans C, Schaller HC. (2006) RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75. Br J Pharmacol, 149 (5): 490-7. [PMID:17001303]

42. Ikubo M, Inoue A, Nakamura S, Jung S, Sayama M, Otani Y, Uwamizu A, Suzuki K, Kishi T, Shuto A et al.. (2015) Structure-Activity Relationships of Lysophosphatidylserine Analogs as Agonists of G-Protein-Coupled Receptors GPR34, P2Y10, and GPR174. J Med Chem, 58 (10): 4204-19. [PMID:25970039]

43. Inoue A, Ishiguro J, Kitamura H, Arima N, Okutani M, Shuto A, Higashiyama S, Ohwada T, Arai H, Makide K et al.. (2012) TGFα shedding assay: an accurate and versatile method for detecting GPCR activation. Nat Methods, 9 (10): 1021-9. [PMID:22983457]

44. Isberg V, Andersen KB, Bisig C, Dietz GP, Bräuner-Osborne H, Gloriam DE. (2014) Computer-aided discovery of aromatic l-α-amino acids as agonists of the orphan G protein-coupled receptor GPR139. J Chem Inf Model, 54 (6): 1553-7. [PMID:24826842]

45. Jensen T, Elster L, Nielsen SM, Poda SB, Loechel F, Volbracht C, Klewe IV, David L, Watson SP. (2014) The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function. Bioorg Med Chem Lett, 24 (22): 5195-8. [PMID:25442311]

46. Jin C, Yin F, Lin M, Li H, Wang Z, Weng J, Liu M, Da Dong X, Qu J, Tu L. (2008) GPR48 regulates epithelial cell proliferation and migration by activating EGFR during eyelid development. Invest Ophthalmol Vis Sci, 49 (10): 4245-53. [PMID:18487371]

47. Jones PG, Nawoschik SP, Sreekumar K, Uveges AJ, Tseng E, Zhang L, Johnson J, He L, Paulsen JE, Bates B, Pausch MH. (2007) Tissue distribution and functional analyses of the constitutively active orphan G protein coupled receptors, GPR26 and GPR78. Biochim Biophys Acta, 1770 (6): 890-901. [PMID:17363172]

48. Kabarowski JH, Zhu K, Le LQ, Witte ON, Xu Y. (2001) Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A. Science, 293 (5530): 702-5. [PMID:11474113]

49. Kamohara M, Matsuo A, Takasaki J, Kohda M, Matsumoto M, Matsumoto S, Soga T, Hiyama H, Kobori M, Katou M. (2005) Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides. Biochem Biophys Res Commun, 330 (4): 1146-52. [PMID:15823563]

50. Kapas S, Catt KJ, Clark AJ. (1995) Cloning and expression of cDNA encoding a rat adrenomedullin receptor. J Biol Chem, 270 (43): 25344-7. [PMID:7592696]

51. Kelly LM, Pereira JP, Yi T, Xu Y, Cyster JG. (2011) EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues. J Immunol, 187 (6): 3026-32. [PMID:21844396]

52. Kennedy SP, Sun D, Oleynek JJ, Hoth CF, Kong J, Hill RJ. (1998) Expression of the rat adrenomedullin receptor or a putative human adrenomedullin receptor does not correlate with adrenomedullin binding or functional response. Biochem Biophys Res Commun, 244 (3): 832-7. [PMID:9535752]

53. Kerkhof HJ, Lories RJ, Meulenbelt I, Jonsdottir I, Valdes AM, Arp P, Ingvarsson T, Jhamai M, Jonsson H, Stolk L, Thorleifsson G, Zhai G, Zhang F, Zhu Y, van der Breggen R, Carr A, Doherty M, Doherty S, Felson DT, Gonzalez A, Halldorsson BV, Hart DJ, Hauksson VB, Hofman A, Ioannidis JP, Kloppenburg M, Lane NE, Loughlin J, Luyten FP, Nevitt MC, Parimi N, Pols HA, Rivadeneira F, Slagboom EP, Styrkársdóttir U, Tsezou A, van de Putte T, Zmuda J, Spector TD, Stefansson K, Uitterlinden AG, van Meurs JB. (2010) A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22. Arthritis Rheum, 62 (2): 499-510. [PMID:20112360]

54. Kim SV, Xiang WV, Kwak C, Yang Y, Lin XW, Ota M, Sarpel U, Rifkin DB, Xu R, Littman DR. (2013) GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science, 340 (6139): 1456-9. [PMID:23661644]

55. Kitamura H, Makide K, Shuto A, Ikubo M, Inoue A, Suzuki K, Sato Y, Nakamura S, Otani Y, Ohwada T et al.. (2012) GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position. J Biochem, 151 (5): 511-8. [PMID:22343749]

56. Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. (2008) Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics, 35 (3): 296-304. [PMID:18796533]

57. Kottyan LC, Collier AR, Cao KH, Niese KA, Hedgebeth M, Radu CG, Witte ON, Khurana Hershey GK, Rothenberg ME, Zimmermann N. (2009) Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner. Blood, 114 (13): 2774-82. [PMID:19641187]

58. Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN. (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA, 107 (4): 1660-5. [PMID:20080636]

59. Ku GM, Pappalardo Z, Luo CC, German MS, McManus MT. (2012) An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production. PLoS Genet, 8 (1): e1002449. [PMID:22253604]

60. Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski WA. (2008) Micromolar concentration of kynurenic acid in rat small intestine. Amino Acids, 35 (2): 503-5. [PMID:18235993]

61. Lansu K, Karpiak J, Liu J, Huang XP, McCorvy JD, Kroeze WK, Che T, Nagase H, Carroll FI, Jin J et al.. (2017) In silico design of novel probes for the atypical opioid receptor MRGPRX2. Nat Chem Biol, 13 (5): 529-536. [PMID:28288109]

62. Lautner RQ, Villela DC, Fraga-Silva RA, Silva N, Verano-Braga T, Costa-Fraga F, Jankowski J, Jankowski V, Sousa F, Alzamora A et al.. (2013) Discovery and characterization of alamandine: a novel component of the Renin-Angiotensin system. Circ Res, 112 (8): 1104-11. [PMID:23446738]

63. Ledent C, Demeestere I, Blum D, Petermans J, Hämäläinen T, Smits G, Vassart G. (2005) Premature ovarian aging in mice deficient for Gpr3. Proc Natl Acad Sci USA, 102 (25): 8922-6. [PMID:15956199]

64. Lembo PM, Grazzini E, Groblewski T, O'Donnell D, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M et al.. (2002) Proenkephalin A gene products activate a new family of sensory neuron--specific GPCRs. Nat Neurosci, 5 (3): 201-9. [PMID:11850634]

65. Leung T, Humbert JE, Stauffer AM, Giger KE, Chen H, Tsai HJ, Wang C, Mirshahi T, Robishaw JD. (2008) The orphan G protein-coupled receptor 161 is required for left-right patterning. Dev Biol, 323 (1): 31-40. [PMID:18755178]

66. 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]

67. Liebscher I, Müller U, Teupser D, Engemaier E, Engel KM, Ritscher L, Thor D, Sangkuhl K, Ricken A, Wurm A et al.. (2011) Altered immune response in mice deficient for the G protein-coupled receptor GPR34. J Biol Chem, 286 (3): 2101-10. [PMID:21097509]

68. Lindfors L, Sundström L, Fröderberg Roth L, Meuller J, Andersson S, Kihlberg J. (2020) Is GPR146 really the receptor for proinsulin C-peptide?. Bioorg Med Chem Lett, 30 (13): 127208. [PMID:32354568]

69. Liu C, Yang XV, Wu J, Kuei C, Mani NS, Zhang L, Yu J, Sutton SW, Qin N, Banie H et al.. (2011) Oxysterols direct B-cell migration through EBI2. Nature, 475 (7357): 519-23. [PMID:21796211]

70. Liu Q, Tang Z, Surdenikova L, Kim S, Patel KN, Kim A, Ru F, Guan Y, Weng HJ, Geng Y, Undem BJ, Kollarik M, Chen ZF, Anderson DJ, Dong X. (2009) Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell, 139 (7): 1353-65. [PMID:20004959]

71. Lobo MK, Cui Y, Ostlund SB, Balleine BW, Yang XW. (2007) Genetic control of instrumental conditioning by striatopallidal neuron-specific S1P receptor Gpr6. Nat Neurosci, 10 (11): 1395-7. [PMID:17934457]

72. Logue SF, Grauer SM, Paulsen J, Graf R, Taylor N, Sung MA, Zhang L, Hughes Z, Pulito VL, Liu F, Rosenzweig-Lipson S, Brandon NJ, Marquis KL, Bates B, Pausch M. (2009) The orphan GPCR, GPR88, modulates function of the striatal dopamine system: a possible therapeutic target for psychiatric disorders?. Mol Cell Neurosci, 42 (4): 438-47. [PMID:19796684]

73. 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]

74. 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 USA, 106 (28): 11685-90. [PMID:19561298]

75. 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]

76. Marazziti D, Di Pietro C, Mandillo S, Golini E, Matteoni R, Tocchini-Valentini GP. (2011) Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine. FASEB J, 25 (6): 2071-81. [PMID:21372109]

77. 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 USA, 104 (23): 9846-51. [PMID:17519329]

78. Marsango S, Barki N, Jenkins L, Tobin AB, Milligan G. (2020) Therapeutic validation of an orphan G protein-coupled receptor: The case of GPR84. Br J Pharmacol, [Epub ahead of print]. [PMID:32869860]

79. Matteson PG, Desai J, Korstanje R, Lazar G, Borsuk TE, Rollins J, Kadambi S, Joseph J, Rahman T, Wink J, Benayed R, Paigen B, Millonig JH. (2008) The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development. Proc Natl Acad Sci USA, 105 (6): 2088-93. [PMID:18250320]

80. 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 USA, 110 (23): 9529-34. [PMID:23690594]

81. 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]

82. 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]

83. 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]

84. 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]

85. 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 (4): 435-46. [PMID:12618218]

86. 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]

87. 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]

88. 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]

89. Osborn O, Oh da Y, McNelis J, Sanchez-Alavez M, Talukdar S, Lu M, Li P, Thiede L, Morinaga H, Kim JJ et al.. (2012) G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. J Clin Invest, 122 (7): 2444-53. [PMID:22653059]

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

91. Pereira JP, Kelly LM, Xu Y, Cyster JG. (2009) EBI2 mediates B cell segregation between the outer and centre follicle. Nature, 460 (7259): 1122-6. [PMID:19597478]

92. Petersen PS, Jin C, Madsen AN, Rasmussen M, Kuhre R, Egerod KL, Nielsen LB, Schwartz TW, Holst B. (2011) Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism. FASEB J, 25 (11): 3803-14. [PMID:21784784]

93. Pringle KG, Tadros MA, Callister RJ, Lumbers ER. (2011) The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: roles in trophoblast invasion and angiogenesis?. Placenta, 32 (12): 956-62. [PMID:22018415]

94. Ramachandran V, Arumugam T, Langley R, Hwang RF, Vivas-Mejia P, Sood AK, Lopez-Berestein G, Logsdon CD. (2009) The ADMR receptor mediates the effects of adrenomedullin on pancreatic cancer cells and on cells of the tumor microenvironment. PLoS ONE, 4 (10): e7502. [PMID:19847298]

95. Rao A, Herr DR. (2017) G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells. Biochim Biophys Acta, 1864 (7): 1318-1327. [PMID:28476646]

96. 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 (Pt 3): 542-9. [PMID:16443751]

97. Robas N, Mead E, Fidock M. (2003) MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J Biol Chem, 278 (45): 44400-4. [PMID:12915402]

98. Ruffner H, Sprunger J, Charlat O, Leighton-Davies J, Grosshans B, Salathe A, Zietzling S, Beck V, Therier M, Isken A et al.. (2012) R-Spondin potentiates Wnt/β-catenin signaling through orphan receptors LGR4 and LGR5. PLoS ONE, 7 (7): e40976. [PMID:22815884]

99. Ruiz-Medina J, Ledent C, Valverde O. (2011) GPR3 orphan receptor is involved in neuropathic pain after peripheral nerve injury and regulates morphine-induced antinociception. Neuropharmacology, 61 (1-2): 43-50. [PMID:21352831]

100. 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]

101. Römpler H, Schulz A, Pitra C, Coop G, Przeworski M, Pääbo S, Schöneberg T. (2005) The rise and fall of the chemoattractant receptor GPR33. J Biol Chem, 280 (35): 31068-75. [PMID:15987686]

102. Setoh M, Ishii N, Kono M, Miyanohana Y, Shiraishi E, Harasawa T, Ota H, Odani T, Kanzaki N, Aoyama K et al.. (2014) Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52. J Med Chem, 57 (12): 5226-37. [PMID:24884590]

103. Seuwen K, Ludwig MG, Wolf RM. (2006) Receptors for protons or lipid messengers or both?. J Recept Signal Transduct Res, 26 (5-6): 599-610. [PMID:17118800]

104. Shinohara T, Harada M, Ogi K, Maruyama M, Fujii R, Tanaka H, Fukusumi S, Komatsu H, Hosoya M, Noguchi Y et al.. (2004) Identification of a G protein-coupled receptor specifically responsive to beta-alanine. J Biol Chem, 279 (22): 23559-64. [PMID:15037633]

105. 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]

106. Solinski HJ, Gudermann T, Breit A. (2014) Pharmacology and signaling of MAS-related G protein-coupled receptors. Pharmacol Rev, 66 (3): 570-97. [PMID:24867890]

107. 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]

108. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]

109. Sugo T, Tachimoto H, Chikatsu T, Murakami Y, Kikukawa Y, Sato S, Kikuchi K, Nagi T, Harada M, Ogi K, Ebisawa M, Mori M. (2006) Identification of a lysophosphatidylserine receptor on mast cells. Biochem Biophys Res Commun, 341 (4): 1078-87. [PMID:16460680]

110. 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]

111. 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]

112. 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]

113. 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]

114. 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]

115. Tobo A, Tobo M, Nakakura T, Ebara M, Tomura H, Mogi C, Im DS, Murata N, Kuwabara A, Ito S et al.. (2015) Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses. PLoS ONE, 10 (6): e0129334. [PMID:26070068]

116. 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]

117. Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, Schernthaner-Reiter MH, Szarek E, Leal LF, Caberg JH et al.. (2014) Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med, 371 (25): 2363-74. [PMID:25470569]

118. Uhlenbrock K, Gassenhuber H, Kostenis E. (2002) Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors. Cell Signal, 14: 941-953. [PMID:12220620]

119. Valdes AM, Spector TD. (2010) The genetic epidemiology of osteoarthritis. Curr Opin Rheumatol, 22 (2): 139-43. [PMID:20090528]

120. Vanti WB, Muglia P, Nguyen T, Cheng R, Kennedy JL, George SR, O'Dowd BF. (2003) Discovery of a null mutation in a human trace amine receptor gene. Genomics, 82: 531-536. [PMID:14559210]

121. Wallrabenstein I, Kuklan J, Weber L, Zborala S, Werner M, Altmüller J, Becker C, Schmidt A, Hatt H, Hummel T et al.. (2013) Human trace amine-associated receptor TAAR5 can be activated by trimethylamine. PLoS ONE, 8 (2): e54950. [PMID:23393561]

122. Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L. (2006) Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem, 281 (31): 22021-8. [PMID:16754668]

123. Wang J, Wu X, Simonavicius N, Tian H, Ling L. (2006) Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J Biol Chem, 281 (45): 34457-64. [PMID:16966319]

124. 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 USA, 105 (16): 6081-6. [PMID:18424556]

125. Witte ON, Kabarowski JH, Xu Y, Le LQ, Zhu K. (2005) Retraction. Science, 307 (5707): 206. [PMID:15653487]

126. Xu Y, Zhu K, Hong G, Wu W, Baudhuin LM, Xiao Y, Damron DS. (2000) Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat Cell Biol, 2 (5): 261-7. [PMID:10806476]

127. Yang LV, Radu CG, Roy M, Lee S, McLaughlin J, Teitell MA, Iruela-Arispe ML, Witte ON. (2007) Vascular abnormalities in mice deficient for the G protein-coupled receptor GPR4 that functions as a pH sensor. Mol Cell Biol, 27 (4): 1334-47. [PMID:17145776]

128. 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 (1): 154-9. [PMID:17214962]

129. Ye C, Zhang Z, Wang Z, Hua Q, Zhang R, Xie X. (2014) Identification of a novel small-molecule agonist for human G protein-coupled receptor 3. J Pharmacol Exp Ther, 349 (3): 437-43. [PMID:24633425]

130. Yin H, Chu A, Li W, Wang B, Shelton F, Otero F, Nguyen DG, Caldwell JS, Chen YA. (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J Biol Chem, 284: 12328-12338. [PMID:19286662]

131. Yosten GL, Kolar GR, Redlinger LJ, Samson WK. (2013) Evidence for an interaction between proinsulin C-peptide and GPR146. J Endocrinol, 218 (2): B1-8. [PMID:23759446]

132. Yu M, Lizarzaburu M, Motani A, Fu Z, Du X, Liu JJ, Jiao X, Lai S, Fan P, Fu A et al.. (2013) Aminopyrazole-Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies. ACS Med Chem Lett, 4 (9): 829-34. [PMID:24900757]

133. Zhang LL, Wang JJ, Liu Y, Lu XB, Kuang Y, Wan YH, Chen Y, Yan HM, Fei J, Wang ZG. (2011) GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala. Neuroscience, 196: 203-14. [PMID:21924326]

134. Zhao P, Sharir H, Kapur A, Cowan A, Geller EB, Adler MW, Seltzman HH, Reggio PH, Heynen-Genel S, Sauer M, Chung TD, Bai Y, Chen W, Caron MG, Barak LS, Abood ME. (2010) Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of extracellular signal-regulated kinase and β-arrestin2 with antinociceptive activity. Mol Pharmacol, 78 (4): 560-8. [PMID:20826425]

135. Zhu K, Baudhuin LM, Hong G, Williams FS, Cristina KL, Kabarowski JH, Witte ON, Xu Y. (2001) Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J Biol Chem, 276 (44): 41325-35. [PMID:11535583]

136. (2006) Retraction. Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat Cell Biol, 8 (3): 299. [PMID:16508674]

Stephen P.H. Alexander Associate Professor in Molecular Pharmacology Life Sciences E Floor University of Nottingham Medical School Nottingham NG7 2UH UK 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 Khuraijam Dhanachandra Singh Department of Molecular Cardiology Lerner Research Institute The Cleveland Clinic Foundation 9500 Euclid Ave. Cleveland, OH 44195 USA 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 (Past Senior Database 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 G. 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