1jbi

Structural highlights

Disease

[COCH_HUMAN] Defects in COCH are the cause of deafness autosomal dominant type 9 (DFNA9) [MIM:601369]. DFNA9 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA9 is characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Deafness is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers.^{[1] [2] [3] [4] [5] [6]}

Function

[COCH_HUMAN] Plays a role in the control of cell shape and motility in the trabecular meshwork.^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Robertson NG, Lu L, Heller S, Merchant SN, Eavey RD, McKenna M, Nadol JB Jr, Miyamoto RT, Linthicum FH Jr, Lubianca Neto JF, Hudspeth AJ, Seidman CE, Morton CC, Seidman JG. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat Genet. 1998 Nov;20(3):299-303. PMID:9806553 doi:10.1038/3118
2. ↑ de Kok YJ, Bom SJ, Brunt TM, Kemperman MH, van Beusekom E, van der Velde-Visser SD, Robertson NG, Morton CC, Huygen PL, Verhagen WI, Brunner HG, Cremers CW, Cremers FP. A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects. Hum Mol Genet. 1999 Feb;8(2):361-6. PMID:9931344
3. ↑ Fransen E, Verstreken M, Verhagen WI, Wuyts FL, Huygen PL, D'Haese P, Robertson NG, Morton CC, McGuirt WT, Smith RJ, Declau F, Van de Heyning PH, Van Camp G. High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene. Hum Mol Genet. 1999 Aug;8(8):1425-9. PMID:10400989
4. ↑ Kamarinos M, McGill J, Lynch M, Dahl H. Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families. Hum Mutat. 2001 Apr;17(4):351. PMID:11295836 doi:10.1002/humu.37
5. ↑ Usami S, Takahashi K, Yuge I, Ohtsuka A, Namba A, Abe S, Fransen E, Patthy L, Otting G, Van Camp G. Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease. Eur J Hum Genet. 2003 Oct;11(10):744-8. PMID:14512963 doi:10.1038/sj.ejhg.5201043
6. ↑ Grabski R, Szul T, Sasaki T, Timpl R, Mayne R, Hicks B, Sztul E. Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin. Hum Genet. 2003 Oct;113(5):406-16. Epub 2003 Aug 20. PMID:12928864 doi:http://dx.doi.org/10.1007/s00439-003-0992-7
7. ↑ Goel M, Sienkiewicz AE, Picciani R, Lee RK, Bhattacharya SK. Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility. PLoS One. 2011;6(8):e23070. doi: 10.1371/journal.pone.0023070. Epub 2011 Aug 23. PMID:21886777 doi:10.1371/journal.pone.0023070
8. ↑ Liepinsh E, Trexler M, Kaikkonen A, Weigelt J, Banyai L, Patthy L, Otting G. NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. EMBO J. 2001 Oct 1;20(19):5347-53. PMID:11574466 doi:10.1093/emboj/20.19.5347