MRGPRX2 Gene - Function, Expression, Mutations & Disease Associations

MRGPRX2 (MAS related GPR family member X2) is a G protein-coupled receptor (GPCR) primarily expressed on mast cells. It functions as a receptor for basic secretagogues, including many cationic drugs, neuropeptides (e.g., substance P, VIP), and host defense peptides. Activation of MRGPRX2 triggers mast cell degranulation, leading to the release of histamine, tryptase, and other inflammatory mediators. This receptor is a key mediator of pseudo-allergic (non-IgE-mediated) drug hypersensitivity reactions and is implicated in chronic urticaria, atopic dermatitis, and pain modulation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GPCR downstream signaling (R-HSA-388396)

• Mast cell degranulation (R-HSA-114608)

• Neuropeptide signaling (R-HSA-375276)

MRGPRX2 is a 7-transmembrane G protein-coupled receptor of 330 amino acids. It is predominantly expressed on mast cells and functions as a receptor for basic secretagogues, including cationic drugs and neuropeptides. Upon ligand binding, MRGPRX2 couples to Gq/11 proteins, leading to phospholipase C activation, intracellular calcium mobilization, and mast cell degranulation. This receptor is a critical mediator of pseudo-allergic drug reactions and is implicated in chronic inflammatory skin diseases. Structural studies reveal a unique binding pocket that accommodates diverse cationic ligands.