Tmc1

TMC1 stands for transmembrane channel-like 1, a protein-coding gene that is conserved across vertebrates and is expressed in sensory tissues, notably the inner ear. The encoded protein is predicted to be a multi-pass membrane component and is a member of the transmembrane channel-like (TMC) family.

In humans and other mammals, TMC1 is prominently expressed in inner ear hair cells, where it is involved in mechanosensory function. The protein is associated with the hair cell mechanotransduction apparatus, which converts mechanical stimuli from sound waves into electrical signals detectable by the nervous system. While the exact molecular arrangement of the channel complex remains under investigation, TMC1 is regarded as a key contributor to the mechanotransduction process and is essential for normal auditory transduction.

Genetic variants in TMC1 are linked to hereditary deafness. Pathogenic mutations can cause autosomal dominant non-syndromic deafness (DFNA36) or autosomal recessive non-syndromic deafness (DFNB7/B4). The clinical presentation can range from congenital profound deafness to progressive hearing loss later in life, reflecting the gene’s critical role in hair cell function.

Research in model organisms has reinforced TMC1’s role in hearing. The Beethoven mouse, which carries a Tmc1 mutation, exhibits progressive hearing loss, and Tmc1 disruption in mice abolishes mechanotransduction currents in hair cells. These findings support a conserved function for TMC1 in vertebrate audition.

Structural studies suggest TMC1 has six transmembrane domains with intracellular N- and C- termini. It is thought to contribute to, or form, a component of the hair cell mechanotransduction channel, interacting with other proteins in the MET complex, though the precise mechanisms remain an active area of study.