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    Topic review

    CLRN1 Gene

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    Submitted by: Vicky Zhou
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    clarin 1

    1. Normal Function

    The CLRN1 gene provides information for making a protein called clarin 1. This protein is probably involved in normal hearing and vision. Clarin 1 has been found in several areas of the body, including sensory cells in the inner ear called hair cells. These cells help transmit sound and motion signals to the brain. This protein is also active in the retina, which is the light-sensing tissue that lines the back of the eye. Although the function of clarin 1 has not been determined, studies suggest that it plays a role in communication between nerve cells (neurons) in the inner ear and in the retina. Clarin 1 may be important for the development and function of synapses, which are junctions between neurons where cell-to-cell communication occurs.

    2. Health Conditions Related to Genetic Changes

    2.1. Usher Syndrome

    At least 15 mutations in the CLRN1 gene have been identified in people with Usher syndrome type III, which is characterized by a combination of hearing loss and vision loss. Some affected individuals also have problems with balance and coordination. CLRN1 gene mutations cause a form of the condition known as Usher syndrome type IIIA (USH3A). This form of Usher syndrome is rare in most countries, although it represents about 40 percent of all Usher syndrome cases in the Finnish population.

    Several CLRN1 gene mutations change single protein building blocks (amino acids) in the clarin 1 protein. In some cases, these mutations lead to the production of an abnormally short version of the protein or prevent the production of any functional clarin 1. Other mutations insert or delete small amounts of DNA in the CLRN1 gene, which probably impairs the normal function of the protein. It is unclear how a missing or altered clarin 1 protein leads to the signs and symptoms of Usher syndrome type IIIA.

    Two particular CLRN1 gene mutations are most common in families of Finnish ancestry. One mutation, sometimes called Finmajor and written as Tyr176Ter or Y176X, leads to the production of an abnormally short, nonfunctional version of clarin 1. The other mutation, written as Met120Lys or M120K and also known as Finminor, substitutes the amino acid lysine for the amino acid methionine at protein position 120. This mutation appears to disrupt the protein's normal function.

    2.2. Retinitis Pigmentosa

    Retinitis pigmentosa

    3. Other Names for This Gene

    • USH3
    • USH3A
    • USH3A_HUMAN
    • Usher syndrome 3A
    • Usher syndrome type 3 protein

    This entry is adapted from https://medlineplus.gov/genetics/gene/clrn1

    References

    1. Adato A, Vreugde S, Joensuu T, Avidan N, Hamalainen R, Belenkiy O, Olender T, Bonne-Tamir B, Ben-Asher E, Espinos C, Millán JM, Lehesjoki AE, Flannery JG,Avraham KB, Pietrokovski S, Sankila EM, Beckmann JS, Lancet D. USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role insensory synapses. Eur J Hum Genet. 2002 Jun;10(6):339-50.
    2. Aller E, Jaijo T, Oltra S, Alió J, Galán F, Nájera C, Beneyto M, Millán JM.Mutation screening of USH3 gene (clarin-1) in Spanish patients with Ushersyndrome: low prevalence and phenotypic variability. Clin Genet. 2004Dec;66(6):525-9.
    3. Fields RR, Zhou G, Huang D, Davis JR, Möller C, Jacobson SG, Kimberling WJ,Sumegi J. Usher syndrome type III: revised genomic structure of the USH3 gene andidentification of novel mutations. Am J Hum Genet. 2002 Sep;71(3):607-17.
    4. Geng R, Geller SF, Hayashi T, Ray CA, Reh TA, Bermingham-McDonogh O, Jones SM,Wright CG, Melki S, Imanishi Y, Palczewski K, Alagramam KN, Flannery JG. Ushersyndrome IIIA gene clarin-1 is essential for hair cell function and associatedneural activation. Hum Mol Genet. 2009 Aug 1;18(15):2748-60. doi:10.1093/hmg/ddp210.
    5. Geng R, Melki S, Chen DH, Tian G, Furness DN, Oshima-Takago T, Neef J, MoserT, Askew C, Horwitz G, Holt JR, Imanishi Y, Alagramam KN. The mechanosensorystructure of the hair cell requires clarin-1, a protein encoded by Usher syndromeIII causative gene. J Neurosci. 2012 Jul 11;32(28):9485-98. doi:10.1523/JNEUROSCI.0311-12.2012.
    6. Isosomppi J, Västinsalo H, Geller SF, Heon E, Flannery JG, Sankila EM.Disease-causing mutations in the CLRN1 gene alter normal CLRN1 proteintrafficking to the plasma membrane. Mol Vis. 2009 Sep 8;15:1806-18.
    7. Joensuu T, Hämäläinen R, Yuan B, Johnson C, Tegelberg S, Gasparini P, Zelante L, Pirvola U, Pakarinen L, Lehesjoki AE, de la Chapelle A, Sankila EM. Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am JHum Genet. 2001 Oct;69(4):673-84.2001 Nov;69(5):1160.
    8. Khan MI, Kersten FF, Azam M, Collin RW, Hussain A, Shah ST, Keunen JE, Kremer H, Cremers FP, Qamar R, den Hollander AI. CLRN1 mutations cause nonsyndromicretinitis pigmentosa. Ophthalmology. 2011 Jul;118(7):1444-8. doi:10.1016/j.ophtha.2010.10.047.
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