Orphan 7-TM receptors

Orphan 7-TM receptors (orphan GPCRs) are receptors for which there are no defined ligands. Traditional GPCRs are characterized by specific ligands and stimuli but orphan receptors are identified receptors but respond to as-yet unidentified endogenous ligands. There are approximately 100 orphan 7-TM receptors, subdivided into three classes: Class A, Class B and Class C.  Orphan G-protein coupled receptors are usually identified by numbers, such as GPR35 and GPR139, and as they are 'de-orphanized' by discovery of a ligand they often maintain this prefix - examples are GPR55 and the the neuropeptide receptor GPR171.

Further reading

Levoye et al (2006) Do orphan G‐protein‐coupled receptors have ligand‐independent functions? New insights from receptor heterodimers.  EMBO Rep 7 1094 PMID: 17077864

Tang et al (2012) Orphan G protein-coupled receptors (GPCRs): biological functions and potential drug targets. Acta Pharmacol Sin 33 363 PMID: 22367282

Ahmad et al (2015) Hunting for the function of orphan GPCRs - beyond the search for the endogenous ligand. Br J Pharmacol. 172(13) 3212 PMID: 25231237