ASIC3 Gene: Acid-Sensing Ion Channel 3 – Function, Expression, and Disease Associations

The ASIC3 gene encodes the acid-sensing ion channel subunit 3, a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. This channel is activated by extracellular protons (low pH) and plays a critical role in pain perception, particularly in response to tissue acidosis associated with inflammation, ischemia, and injury. ASIC3 is predominantly expressed in sensory neurons of the peripheral nervous system and contributes to nociception, mechanosensation, and modulation of inflammatory pain.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Acid-sensing ion channel signaling

• Pain sensation and modulation

• Inflammatory mediator regulation of TRP channels (cross-talk)

• Nociception pathway

The ASIC3 protein is a 531-amino acid subunit that assembles into homo- or heterotrimeric channels. It is activated by a drop in extracellular pH, leading to sodium influx and neuronal depolarization. ASIC3 is highly expressed in sensory neurons, where it contributes to the detection of tissue acidosis and pain. It also plays roles in mechanosensation and in the modulation of inflammatory pain. The protein has two transmembrane domains, a large extracellular loop, and intracellular N- and C-termini. Post-translational modifications and interactions with other proteins (e.g., PICK1, STOM) regulate its trafficking and function.