| Clarin 1 | |
|---|---|
| Gene | CLRN1 |
| UniProt | Q9NYQ5 |
| PDB | AlphaFold predicted |
| Mol. Weight | 25 kDa |
| Localization | Hair cell stereocilia, synaptic vesicles |
| Family | Clarin family, tetraspanin-like |
| Diseases | Usher Syndrome Type 3, Non-syndromic Deafness |
Clarin 1 (encoded by CLRN1) is a 25 kDa tetraspanin-like membrane protein essential for the structure and function of hair cell stereocilia in the inner ear and photoreceptor ribbon synapses in the retina. Mutations in CLRN1 cause Usher syndrome type 3 (USH3), characterized by progressive hearing loss and retinitis pigmentosa[1][2].
Clarin-1 is expressed in the stereocilia of inner ear hair cells, where it localizes to the plasma membrane and regulates the maintenance of hair bundle structure. It is also present in ribbon synapses of photoreceptors and inner hair cells, where it participates in synaptic vesicle trafficking[3][4].
Clarin-1 contains four transmembrane domains with intracellular N- and C-termini:
This structure is similar to tetraspanins, suggesting a role in organizing membrane microdomains.
Clarin-1 is essential for[5][2:1]:
Clarin-1 is critical for:
CLRN1 mutations cause USH3, characterized by[2:2]:
Over 30 pathogenic mutations have been identified in CLRN1, including:
Some CLRN1 mutations cause isolated deafness without retinal degeneration:
In the retina, clarin-1 dysfunction leads to[3:2]:
AAV-mediated CLRN1 delivery has shown promise in animal models:
For patients with advanced hearing loss:
When Clarin-1 is referenced in disease pages:
Kenny de M, et al. Clarin-1 is essential for hearing and vision. Human Molecular Genetics. 2015. ↩︎ ↩︎ ↩︎
Zallocchi M, et al. Clarin-1 distribution and function in the retina. Investigative Ophthalmology & Visual Science. 2016. ↩︎ ↩︎ ↩︎
Starr CJ, et al. Clarin-1 in auditory ribbon synapses. Journal of the Association for Research in Otolaryngology. 2015. ↩︎ ↩︎
Geleoc GGS, et al. Clarin-1, a protein defective in Usher syndrome, regulates hair bundle stiffness. Nature Medicine. 2008. ↩︎