Table 2.
Class A Orphan GPCR with limited pharmacological or phenotypic profiles
| Nomenclature | HGNC, UniProt | Principal transduction | Comment |
|---|---|---|---|
| GPR19 | GPR19, Q15760 | – | – |
| GPR21 | GPR21, Q99679 | Gq/11 | Gpr21 knockout mice were resistant to diet-induced obesity, exhibiting an increase in glucose tolerance and insulin sensitivity and a modest lean phenotype 74. |
| GPR25 | GPR25, O00155 | – | – |
| GPR27 | GPR27, Q9NS67 | Gq/G11 | Knockdown of Gpr27 reduces endogenous mouse insulin promotor activity and glucose stimulated insulin secretion 52. |
| GPR33 | GPR33, Q49SQ1 | Gi/Go | GPR33 is a pseudogene in most individuals, containing a premature stop codon within the coding sequence of the second intracellular loop 83. |
| GPR37L1 | GPR37L1, O60883 | Gi/Go | – |
| GPR45 | GPR45, Q9Y5Y3 | – | – |
| GPR52 | GPR52, Q9Y2T5 | – | – |
| GPR62 | GPR62, Q9BZJ7 | – | – |
| GPR78 | GPR78, Q96P69 | Gs | GPR78 has been reported to be constitutively active, coupled to elevated cAMP production 40. |
| GPR82 | GPR82, Q96P67 | – | Mice with Gpr82 knockout have a lower body weight and body fat content associated with reduced food intake, decreased serum triglyceride levels, higher insulin sensitivity and glucose tolerance 22. |
| GPR83 | GPR83, Q9NYM4 | – | One isoform has been implicated in the induction of CD4(+)CD25(+) regulatory T cells (Tregs) during inflammatory immune responses 29. |
| GPR85 | GPR85, P60893 | – | Proposed to regulate of hippocampal adult neurogenesis and neurogenesis-dependent learning and memory 14. |
| GPR135 | GPR135, Q8IZ08 | – | – |
| GPR139 | GPR139, Q6DWJ6 | Gq/G11 | – |
| GPR141 | GPR141, Q7Z602 | – | – |
| GPR142 | GPR142, Q7Z601 | – | – |
| GPR146 | GPR146, Q96CH1 | – | Yosten et al. demonstrated inhibition of proinsulin C-peptide (INS, P01308)-induced stimulation of cFos expression folllowing knockdown of GPR146 in KATOIII cells, suggesting proinsulin C-peptide as an endogenous ligand of the receptor 107. |
| GPR148 | GPR148, Q8TDV2 | – | – |
| GPR150 | GPR150, Q8NGU9 | – | – |
| GPR151 | GPR151, Q8TDV0 | – | GPR151 responded to galanin with an EC50 value of 2 μM, suggesting that the endogenous ligand shares structural features with galanin (GAL, P22466) 34. |
| GPR152 | GPR152, Q8TDT2 | – | – |
| GPR153 | GPR153, Q6NV75 | – | – |
| GPR160 | GPR160, Q9UJ42 | – | – |
| GPR162 | GPR162, Q16538 | – | – |
| GPR171 | GPR171, O14626 | – | GPR171 has been shown to be activated by endogenous peptide BigLEN. This receptor-peptide interaction is believed to be involved in regulating feeding and metabolism responses 26. |
| GPR173 | GPR173, Q9NS66 | – | – |
| GPR174 | GPR174, Q9BXC1 | Gs | Reported to respond to lysophosphatidylserine (pEC50 7.1) 38. |
| GPR176 | GPR176, Q14439 | – | – |
| GPR182 | GPR182, O15218 | – | Rat GPR182 was first proposed as adrenomedullin receptor 43. However, it was later reported that rat and human GPR182 did not respond to adrenomedullin 45 and GPR182 is not currently considered to be a genuine adrenomedullin receptor 31. |
| MAS1L | MAS1L, P35410 | – | – |
| MRGPRX3 | MRGPRX3, Q96LB0 | Gq/G11 | – |
| MRGPRX4 | MRGPRX4, Q96LA9 | Gq/G11 | – |
| MRGPRE | MRGPRE, Q86SM8 | – | – |
| MRGPRF | MRGPRF, Q96AM1 | – | MRGPRF has been reported to respond to stimulation by angiotensin metabolites 25. |
| MRGPRG | MRGPRG, Q86SM5 | – | – |
| OPN3 | OPN3, Q9H1Y3 | – | – |
| OPN5 | OPN5, Q6U736 | Gi/Go | Evidence indicates OPN5 triggers a UV-sensitive Gi-mediated signalling pathway in mammalian tissues 49. |
| P2RY8 | P2RY8, Q86VZ1 | – | – |