CLRN1 gene


Gene (OMIM no.)
Function of gene/protein
  • Transmembrane protein
  • Required for the normal development and maintenance of the inner ear stereocilia hair cells
  • Localises to the retinal Müller glial cells
  • May be involved in synapse development and function
Clinical phenotype (with OMIM phenotype no.)
  • Autosomal recessive
Ocular features
Visual function
  • Nyctalopia typically starting after adolescence
  • Peripheral visual field loss
  • Loss of central and colour vision in later life
Systemic features Usher syndrome
  • Progressive bilateral sensorineural hearing loss with variable onset (post-lingual) and severity
  • Vestibular abnormalities present in some patients
Key investigations
  • Pure tone audiometry
  • Electrophysiology
  • Fundus autofluorescence (FAF): a ring of hyper-AF in the macula
  • Optical coherence tomography (OCT): progressive loss of outer retinal structures which spares the fovea initially; cystoid macular oedema may be detected
  • Kinetic perimetry
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal and deafness)
  • Whole exome sequencing
  • Whole genome sequencing
  • Targeted exome sequencing
Therapies under research
Further information

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  1. Joensuu T, Hamalainen R, Yuan B, et al. Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am J Hum Genet. 2001;69(4):673-684.
  2. Adato A, Vreugde S, Joensuu T, et al. USH3A transcripts encode clarin-1, a four- transmembrane-domain protein with a possible role in sensory synapses. Eur J Hum Genet. 2002;10(6):339-350.
  3. Khan MI, Kersten FFJ, Azam M, et al. CLRN1 Mutations Cause Nonsyndromic Retinitis Pigmentosa. Ophthalmology. 2011;118(7):1444-1448.
  4. Dinculescu A, Stupay RM, Deng WT, et al. AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy. PLoS One. 2016;11(2):e0148874.
  5. Geng R, Omar A, Gopal SR, et al. Modeling and Preventing Progressive Hearing Loss in Usher Syndrome III. Sci Rep. 2017;7(1):13480.
  6. Dulon D, Papal S, Patni P, et al. Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome. The Journal of clinical investigation. 2018;128(8):3382-3401.
  7. György B, Meijer EJ, Ivanchenko MV, et al. Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate. Molecular therapy Methods & clinical development. 2019;13:1-13.
  8. Alagramam KN, Gopal SR, Geng R, et al. A small molecule mitigates hearing loss in a mouse model of Usher syndrome III. Nat Chem Biol. 2016;12(6):444-451.

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Updated on August 19, 2022
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