Class A Orphans with no pharmacology | G protein-coupled receptors

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G protein-coupled receptors
Class A Orphans
Class A Orphans with no pharmacology

Class A Orphans with no pharmacology C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Class A Orphan GPCRs identified by NC-IUPHAR[8].

Receptors

Targets of relevance to immunopharmacology are highlighted in blue

GPR20 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	91
Nomenclature	GPR20
Previous and unofficial names	Gpcr5-1 \| P2Y4 \| G protein-coupled receptor 5-1
Genes	GPR20 (Hs), Gpr20 (Mm), Gpr20 (Rn)
Ensembl ID	ENSG00000204882 (Hs), ENSMUSG00000045281 (Mm), ENSRNOG00000007795 (Rn)
UniProtKB AC	Q99678 (Hs), Q8BYC4 (Mm), O35797 (Rn)
Principal transduction	G_i/G_o family
Comment	Reported to inhibit adenylyl cyclase constitutively through G_i/o [9]. GPR20 deficient mice exhibit hyperactivity characterised by increased total distance travelled in an open field test [3].

GPR21 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	92
Nomenclature	GPR21
Genes	GPR21 (Hs), Gpr21 (Mm), Gpr21 (Rn)
Ensembl ID	ENSG00000188394 (Hs), ENSMUSG00000053164 (Mm), ENSRNOG00000042269 (Rn)
UniProtKB AC	Q99679 (Hs), Q8BX79 (Mm)
Principal transduction	-
Comment	Gpr21 knockout mice were resistant to diet-induced obesity, exhibiting an increase in glucose tolerance and insulin sensitivity, as well as a modest lean phenotype [18].

GPR22 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	93
Nomenclature	GPR22
Genes	GPR22 (Hs), Gpr22 (Mm), Gpr22 (Rn)
Ensembl ID	ENSG00000172209 (Hs), ENSMUSG00000044067 (Mm), ENSRNOG00000008423 (Rn)
UniProtKB AC	Q99680 (Hs), Q8BZL4 (Mm), D4A3U0 (Rn)
Principal transduction	G_i/G_o family
Comment	Gene disruption results in increased severity of functional decompensation following aortic banding [1]. Identified as a susceptibility locus for osteoarthritis [7,11,20].

GPR26 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	96
Nomenclature	GPR26
Genes	GPR26 (Hs), Gpr26 (Mm), Gpr26 (Rn)
Ensembl ID	ENSG00000154478 (Hs), ENSMUSG00000040125 (Mm), ENSRNOG00000047057 (Rn)
UniProtKB AC	Q8NDV2 (Hs), Q8BZA7 (Mm), Q9QXI3 (Rn)
Principal transduction	G_s family
Comment	Has been reported to activate adenylyl cyclase constitutively through G_s [10]. Gpr26 knockout mice show increased levels of anxiety and depression-like behaviours [21].

GPR27 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	97
Nomenclature	GPR27
Previous and unofficial names	super conserved receptor expressed in brain 1 \| SREB1
Genes	GPR27 (Hs), Gpr27 (Mm), Gpr27 (Rn)
Ensembl ID	ENSG00000170837 (Hs), ENSMUSG00000072875 (Mm), ENSRNOG00000010880 (Rn)
UniProtKB AC	Q9NS67 (Hs), O54897 (Mm), Q9JJH3 (Rn)
Principal transduction	G_q/G₁₁ family
Comment	Knockdown of Gpr27 reduces endogenous mouse insulin promotor activity and glucose-stimulated insulin secretion [13].

GPR45 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	106
Nomenclature	GPR45
Previous and unofficial names	PSP24 \| high-affinity lysophosphatidic acid receptor \| PSP24alpha \| PSP24A
Genes	GPR45 (Hs), Gpr45 (Mm), Gpr45 (Rn)
Ensembl ID	ENSG00000135973 (Hs), ENSMUSG00000041907 (Mm), ENSRNOG00000016446 (Rn)
UniProtKB AC	Q9Y5Y3 (Hs), Q9EQQ4 (Mm)
Principal transduction	-

GPR50 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	107
Nomenclature	GPR50
Previous and unofficial names	MTNRL \| H9 \| Mel1c \| melatonin-related receptor
Genes	GPR50 (Hs), Gpr50 (Mm), Gpr50 (Rn)
Ensembl ID	ENSG00000102195 (Hs), ENSMUSG00000056380 (Mm), ENSRNOG00000011335 (Rn)
UniProtKB AC	Q13585 (Hs), O88495 (Mm), Q62953 (Rn)
Principal transduction	-
Comment	GPR50 is structurally related to MT₁ and MT₂ melatonin receptors, with which it heterodimerises constitutively and specifically [16]. Gpr50 knockout mice display abnormal thermoregulation and are much more likely than wild-type mice to enter fasting-induced torpor [2].

GPR62 Show summary »« Hide summary More detailed page go icon to follow link

GPR78 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	116
Nomenclature	GPR78
Genes	GPR78 (Hs)
Ensembl ID	ENSG00000155269 (Hs)
UniProtKB AC	Q96P69 (Hs)
Principal transduction	G_s family
Comment	GPR78 has been reported to be constitutively active, coupled to elevated cAMP production [10].

GPR79 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	117
Nomenclature	GPR79
Previous and unofficial names	GPR79P \| G protein-coupled receptor 79, pseudogene
Genes	GPR79 (Hs)
Ensembl ID	ENSG00000232374 (Hs)
Principal transduction	-

GPR82 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	118
Nomenclature	GPR82
Genes	GPR82 (Hs), Gpr82 (Mm)
Ensembl ID	ENSG00000171657 (Hs), ENSMUSG00000047678 (Mm)
UniProtKB AC	Q96P67 (Hs), Q8BZR0 (Mm)
Principal transduction	-
Comment	Mice with Gpr82 knockout have a lower body weight and body fat content associated with reduced food intake, decreased serum triglyceride levels, as well as higher insulin sensitivity and glucose tolerance [6].

GPR135 Show summary »« Hide summary More detailed page go icon to follow link

GPR141 Show summary »« Hide summary More detailed page go icon to follow link

GPR148 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	134
Nomenclature	GPR148
Previous and unofficial names	BTR \| PGR6 \| brain and testis restricted GPCR
Genes	GPR148 (Hs)
Ensembl ID	ENSG00000173302 (Hs)
UniProtKB AC	Q8TDV2 (Hs)
Principal transduction	-

GPR149 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	135
Nomenclature	GPR149
Previous and unofficial names	IEDA \| G-protein coupled receptor PGR10 \| induced early in differentiating astrocytes gene protein
Genes	GPR149 (Hs), Gpr149 (Mm), Gpr149 (Rn)
Ensembl ID	ENSG00000174948 (Hs), ENSMUSG00000043441 (Mm), ENSRNOG00000014793 (Rn)
UniProtKB AC	Q86SP6 (Hs), Q3UVY1 (Mm), Q924Y8 (Rn)
Principal transduction	-
Comment	Gpr149 knockout mice displayed increased fertility and enhanced ovulation, with increased levels of FSH receptor and cyclin D2 mRNA levels [5].

GPR150 Show summary »« Hide summary More detailed page go icon to follow link

GPR152 Show summary »« Hide summary More detailed page go icon to follow link

GPR153 Show summary »« Hide summary More detailed page go icon to follow link

GPR161 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	141
Nomenclature	GPR161
Previous and unofficial names	G-protein coupled receptor RE2
Genes	GPR161 (Hs), Gpr161 (Mm), Gpr161 (Rn)
Ensembl ID	ENSG00000143147 (Hs), ENSMUSG00000040836 (Mm), ENSRNOG00000003073 (Rn)
UniProtKB AC	Q8N6U8 (Hs), B2RPY5 (Mm), F1M5Q2 (Rn)
Principal transduction	-
Comment	A C-terminal truncation (deletion) mutation in Gpr161 causes congenital cataracts and neural tube defects in the vacuolated lens (vl) mouse mutant [17]. The mutated receptor is associated with cataract, spina bifida and white belly spot phenotypes in mice [12]. Gene disruption is associated with a failure of asymmetric embryonic development in zebrafish [15].

GPR176 Show summary »« Hide summary More detailed page go icon to follow link

MRGPRE Show summary »« Hide summary More detailed page go icon to follow link

MRGPRG Show summary »« Hide summary More detailed page go icon to follow link

MRGPRX3 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	158
Nomenclature	MRGPRX3
Previous and unofficial names	MrgA \| Mrgpra \| Mrga10 \| SNSR1 [14] \| Sensory neuron-specific G protein-coupled receptor 1
Genes	MRGPRX3 (Hs)
Ensembl ID	ENSG00000179826 (Hs)
UniProtKB AC	Q96LB0 (Hs)
Principal transduction	G_q/G₁₁ family

Comments

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References

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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. 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.

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

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. 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]

18. 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]

19. 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]

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

21. 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]

How to cite this family page

Database page citation:

Class A Orphans with no pharmacology. Accessed on 18/06/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1111.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.