G protein-coupled receptor class C group 6 member A (GPRC6A)

G protein-coupled receptor class C group 6 member A (GPRC6A) is a member of the class C G protein-coupled receptor superfamily characterized by a seven-transmembrane domain structure and a large N-terminal extracellular domain with an amino acid-sensing motif[4][2][1]. It is activated by multiple ligands, including various L-α-amino acids, divalent cations (such as calcium and magnesium), and the bone-derived hormone osteocalcin, and functions as a membrane androgen receptor[1][2][5]. GPRC6A mediates rapid, non-genomic responses to testosterone and is implicated in the regulation of testosterone synthesis, metabolic sensing, and coordination of anabolic signals[1][2]. The receptor is associated with several physiological and pathological processes, including prostate cancer progression and hyperparathyroidism, and plays a role in cellular signaling pathways such as MAPK and mTORC1 activation[1][2][4]. Although extensively studied in animal models, human GPRC6A differs in trafficking and function, as most of the receptor is intracellularly retained rather than cell-surface localized[3][5]. No drugs are currently approved for clinical use targeting GPRC6A, and there are no widely accepted biomarkers or specific antagonists for this receptor[5].

Other names

G protein-coupled receptor family C group 6 member AhGPRC6AhGPCR33GPCR33bA86F4.3GPCR6AGPRC6 receptorG protein-coupled receptor, family C, group 6, member ASeven transmembrane helix receptor (predicted)

Agonist binding (amino acids, osteocalcin, cations) leads to activation of G-protein signaling pathways (notably Gq/G11 and Gi), which can stimulate downstream signaling such as phospholipase C activation and CREB-dependent gene expression for steroidogenesis[2][5][1]. In prostate cells, mediates non-genomic androgen responses, including activation of MAPK and mTORC1 signaling pathways[1].