Mutations of MRGPRX2, drug sensitivity, and genetic markers related to disease

Mast cells (MCs) express the novel class A Mas-related G protein-coupled receptor X2 (MRGPRX2). Additionally, neurons and other leukocytes including basophils express MRGPRX2. MC activation dependent on IgE is a well-established and extensively researched mechanism of type I hypersensitivity and allergic reactions. It was not until MRGPRX2 was identified as the receptor in charge of pseudo-allergy or IgE-independent MC activation that non-IgE-mediated MC degranulation was defined and acknowledged, despite the known clinical phenotype of "pseudo-allergy." The identification and characterization of MRGPRX2 subsequently solved the enigma of non-IgE-mediated (pseudo-allergic) response. Studies indicate that MRGPRX2 is involved in the manifestation of symptoms in atopic dermatitis, neurogenic inflammation, and chronic urticaria. In 2021, it was reported that naturally occurring missense mutations in the <i>MRGPRX2</i> gene could lead to a loss-of-function phenotype affecting MC activation by a wide range of ligands. Mutations resulting in gain of function have also been reported. The likelihood and features of anaphylactic reactions brought on by the MRGPRX2 receptor are affected by mutations in the <i>MRGPRX2</i> gene. Changes in receptor function brought on by these mutations may be a factor in diseases like chronic urticaria and other disorders involving MCs. It is therefore necessary to ascertain not just the distribution of these mutations but also their potential implications in allergies and other illnesses. Creating a potent high-affinity antagonist is one of the best strategies to block the MRGPRX2 receptor. This review presents a current in-depth analysis of how these changes in the <i>MRGPRX2</i> gene affect treatment responsiveness and illness susceptibility; it also highlights the significance of further research into the potential roles of gain-of-function and loss-of-function mutations of <i>MRGPRX2</i> in drug-induced anaphylaxis.