Transmembrane channel-like protein 1 (TMC1)

Transmembrane channel-like protein 1 is a mechanosensitive ion channel localized to cochlear hair cells, where it forms the ion-conducting pore of the mechanoelectrical transducer (MET) channel critical for sound detection. TMC1 assembles as a dimer with each subunit containing 10 transmembrane helices, forming a structure similar to TMEM16 and OSCA family channels. Mutations disrupting pore function reduce calcium permeability, trigger apoptosis of auditory hair cells, and lead to congenital or progressive hearing loss in humans and mice. TMC1 is mechanistically involved in the initial step of sensory transduction by gating in response to mechanical force delivered by tip links in hair cells, thus converting sound waves into electrical signals. Accessory proteins (e.g., TMIE, LHFPL5) help localize and regulate TMC1 at the stereocilia tips.

Other names

Transmembrane cochlear-expressed protein 1DFNA36DFNB7DFNB11transmembrane channel-like protein 1transmembrane, cochlear expressed, 1TMC1

For gene therapy: Restoration of TMC1 function in cochlear hair cells to recover auditory transduction. For mechanosensitive channel modulators: Hypothetical modulation of channel gating (not yet established drugs).