FCER1A

FCER1A is the gene that encodes the alpha chain of the high-affinity receptor for immunoglobulin E (IgE), known as FcεRIα. This subunit binds IgE with high affinity and, together with the beta and gamma signaling subunits, forms the FcεRI complex that is expressed on the surface of mast cells and basophils and, to a lesser extent, on certain dendritic cells and other antigen-presenting cells. The extracellular region of FcεRIα contains the IgE-binding domain, and its cytoplasmic region interacts with the signaling components to initiate cellular activation.

Upon allergen exposure, cross-linking of IgE bound to FcεRI triggers receptor activation. In mast cells and basophils, this leads to rapid degranulation with release of histamine and other mediators, as well as synthesis of leukotrienes and prostaglandins, driving early-phase allergic reactions. It also influences antigen presentation and cytokine production by FcεRI-expressing cells, contributing to the persistence and amplification of inflammation in allergic disease.

Genetic variation in FCER1A has been associated with serum IgE levels and atopy in multiple populations, suggesting that FCER1A affects susceptibility to allergic diseases by modulating receptor expression or IgE binding. Clinically, therapies that reduce IgE levels, such as anti-IgE antibodies, indirectly downregulate FcεRI expression and signaling, reducing allergic responsiveness.

FCER1A is part of the Fc receptor gene family and is conserved across mammals. The receptor’s signaling is mediated by associated gamma subunits containing ITAMs, which propagate the activation cascade upon receptor cross-linking.