Mas-related G-protein coupled receptor member X3 (MRGPRX3)

Mas-related G-protein coupled receptor member X3 (MRGPRX3) is a primate-specific orphan receptor in the delta branch of the rhodopsin-like class A GPCR family. It is predominantly expressed in sensory neurons as well as some immune cells and is part of a subfamily that includes MRGPRX1, -2, -3, and -4. MRGPRX3 is structurally unique compared to canonical GPCRs, with key differences in its ligand binding pocket and lack of certain conserved motifs. While its closest homologs, especially MRGPRX1 and MRGPRX2, have well-studied roles in mediating pain, itch, neuroinflammation, mast cell responses, and pseudoallergic reactions, the specific functions of MRGPRX3 are less well elucidated. The MRGPRX family receives diverse small molecule and peptide ligands and is of high interest as a non-opioid therapeutic target for pain and related conditions, although no selective clinical drugs or biomarkers for MRGPRX3 have yet been established.

Other names

Mas-related GPR family member X3MRGX3SNSR1SNSR2Sensory neuron-specific G-protein coupled receptor 1Sensory neuron-specific G-protein coupled receptor 2G protein-coupled receptor MRGX3G protein-coupled receptor SNSR1G protein-coupled receptor SNSR2mas-related GPCR member X3

Drugs targeting MRGPRX family generally act as agonists or antagonists at the receptor, modulating pain, itch, or immune signaling via G protein-coupling and downstream effectors. Mechanisms for MRGPRX3 itself are likely similar, but specific drug-receptor interactions have not been delineated.