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Gene Review

USH1C  -  Usher syndrome 1C (autosomal recessive,...

Homo sapiens

Synonyms: AIE-75, AIE75, Antigen NY-CO-38/NY-CO-37, Autoimmune enteropathy-related antigen AIE-75, DFNB18, ...
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Disease relevance of USH1C


High impact information on USH1C


Chemical compound and disease context of USH1C


Biological context of USH1C

  • In another family, haplotype segregation was consistent with linkage to USH1C [7].
  • We performed mutation screening by single strand conformation polymorphism (SSCP) analysis and direct sequencing on 33 USH1 patients previously excluded for USH1B and USH1C [8].
  • In these protein-protein complexes harmonin acts as the scaffold protein binding these USH1 molecules via its PDZ domains [9].
  • None carried any mutations in these exons of USH1C [10].
  • In addition, a 45-bp variable number of tandem repeat (VNTR) polymorphism was found in intron 5 of USH1C [11].

Anatomical context of USH1C

  • Colocalization of Pcdh15 with harmonin was found at the base of the photoreceptor outer segment, where newly synthesized disk membranes are present [9].
  • Our findings show that USH1C mutations can also cause non-syndromic deafness and that some harmonin isoforms are specifically required for inner ear function [10].
  • Analysis of all the markers in the USH1C region flanked by D11S1397 and D11S1888 on the J1 somatic cell hybrid panel localized USH1C to the upper half of chromosome 11p14 [12].
  • AIE-75 was predominantly distributed in the epithelial cells of the luminal surface and the upper half of the crypts of the intestine and in the proximal renal tubulus [13].
  • Three of the 48 antigens showed a differential pattern of mRNA expression, with NY-CO-27 (galectin-4) expressed primarily in gastrointestinal tract, and NY-CO-37 and -38 showing a pattern of tissue-specific isoforms [14].

Associations of USH1C with chemical compounds

  • We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network [15].
  • In one family, congenital profound deafness without RP was associated with a C to G transversion in the alternatively spliced exon D, predicting an arginine to proline substitution at codon 608 in the proline-, serine- and threonine-rich region of harmonin [10].
  • Screening of proteins that bound to PDZ domains of AIE-75 by a yeast two hybrid system showed that three serine/threonine phosphatase catalytic subunits (PP2AC-alpha, PP2AC-beta, and PPP6C) could bind to AIE-75 [3].
  • We have cloned a human cDNA, DELGEF (deafness locus associated putative guanine nucleotide exchange factor), derived from a 225 kb genomic sequence of chromosome 11p14, critical for the Usher 1C syndrome and for DFNB18, a locus for non-syndromic sensorineural deafness [16].
  • Otog, the gene encoding otogelin, a glycoprotein specific to all the acellular membranes of the inner ear, is also localized to mouse Chr 7, but in a region more proximal to the twister mutation, homologous to the short arm of human Chr 11 (11p15) carrying the two deafness loci, DFNB 18 and USH C [17].

Physical interactions of USH1C

  • MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL [18].

Other interactions of USH1C

  • A previous screening of 18 unrelated USH1 patients, without a detected MYO7A mutation, for the three USH1C mutations described to date had demonstrated the presence of the 238-239insC mutation in the heterozygous state in four of them [19].
  • Recently, the USH1C gene was shown to encode harmonin, a PDZ domain-containing protein [19].
  • By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin [20].
  • Since the MCC1 does not bind to AIE-75 and the MCC2 displays different expression patterns in various organs compared to MCC1, they appear to play distinct roles in cells [18].
  • PURPOSE: To search for patients with Usher syndrome type IC among those with Usher syndrome type I who reside in New England. METHODS: Genotype analysis of microsatellite markers closely linked to the USH1C locus was done using the polymerase chain reaction [21].

Analytical, diagnostic and therapeutic context of USH1C


  1. A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene. Bitner-Glindzicz, M., Lindley, K.J., Rutland, P., Blaydon, D., Smith, V.V., Milla, P.J., Hussain, K., Furth-Lavi, J., Cosgrove, K.E., Shepherd, R.M., Barnes, P.D., O'Brien, R.E., Farndon, P.A., Sowden, J., Liu, X.Z., Scanlan, M.J., Malcolm, S., Dunne, M.J., Aynsley-Green, A., Glaser, B. Nat. Genet. (2000) [Pubmed]
  2. Contig maps and genomic sequencing identify candidate genes in the usher 1C locus. Higgins, M.J., Day, C.D., Smilinich, N.J., Ni, L., Cooper, P.R., Nowak, N.J., Davies, C., de Jong, P.J., Hejtmancik, F., Evans, G.A., Smith, R.J., Shows, T.B. Genome Res. (1998) [Pubmed]
  3. Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells. Hirai, A., Tada, M., Furuuchi, K., Ishikawa, S., Makiyama, K., Hamada, J., Okada, F., Kobayashi, I., Fukuda, H., Moriuchi, T. Cancer Lett. (2004) [Pubmed]
  4. Construction of a YAC contig encompassing the Usher syndrome type 1C and familial hyperinsulinism loci on chromosome 11p14-15.1. Ayyagari, R., Nestorowicz, A., Li, Y., Chandrasekharappa, S., Chinault, C., van Tuinen, P., Smith, R.J., Hejtmancik, J.F., Permutt, M.A. Genome Res. (1996) [Pubmed]
  5. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B.J., Slim, R., Petit, C. Nat. Genet. (2000) [Pubmed]
  6. Structure, diversity, and evolution of the 45-bp VNTR in intron 5 of the USH1C gene. Savas, S., Frischhertz, B., Batzer, M.A., Deininger, P.L., Keats, B.J. Genomics (2004) [Pubmed]
  7. Haplotype analysis of the USH1D locus and genotype-phenotype correlations. Liu, X.Z., Blanton, S.H., Bitner-Glindzicz, M., Pandya, A., Landa, B., MacArdle, B., Rajput, K., Bellman, S., Webb, B.T., Ping, X., Smith, R.J., Nance, W.E. Clin. Genet. (2001) [Pubmed]
  8. Identification and in vitro expression of novel CDH23 mutations of patients with Usher syndrome type 1D. von Brederlow, B., Bolz, H., Janecke, A., La O Cabrera, A., Rudolph, G., Lorenz, B., Schwinger, E., Gal, A. Hum. Mutat. (2002) [Pubmed]
  9. Photoreceptor expression of the Usher syndrome type 1 protein protocadherin 15 (USH1F) and its interaction with the scaffold protein harmonin (USH1C). Reiners, J., Märker, T., Jürgens, K., Reidel, B., Wolfrum, U. Mol. Vis. (2005) [Pubmed]
  10. Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness. Ouyang, X.M., Xia, X.J., Verpy, E., Du, L.L., Pandya, A., Petit, C., Balkany, T., Nance, W.E., Liu, X.Z. Hum. Genet. (2002) [Pubmed]
  11. The USH1C 216G-->A mutation and the 9-repeat VNTR(t,t) allele are in complete linkage disequilibrium in the Acadian population. Savas, S., Frischhertz, B., Pelias, M.Z., Batzer, M.A., Deininger, P.L., Keats, B.B. Hum. Genet. (2002) [Pubmed]
  12. Fine mapping of the usher syndrome type IC to chromosome 11p14 and identification of flanking markers by haplotype analysis. Ayyagari, R., Li, Y., Smith, R.J., Pelias, M.Z., Hejtmancik, J.F. Mol. Vis. (1995) [Pubmed]
  13. Identification of an autoimmune enteropathy-related 75-kilodalton antigen. Kobayashi, I., Imamura, K., Kubota, M., Ishikawa, S., Yamada, M., Tonoki, H., Okano, M., Storch, W.B., Moriuchi, T., Sakiyama, Y., Kobayashi, K. Gastroenterology (1999) [Pubmed]
  14. Characterization of human colon cancer antigens recognized by autologous antibodies. Scanlan, M.J., Chen, Y.T., Williamson, B., Gure, A.O., Stockert, E., Gordan, J.D., Türeci, O., Sahin, U., Pfreundschuh, M., Old, L.J. Int. J. Cancer (1998) [Pubmed]
  15. Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Reiners, J., van Wijk, E., Märker, T., Zimmermann, U., Jürgens, K., te Brinke, H., Overlack, N., Roepman, R., Knipper, M., Kremer, H., Wolfrum, U. Hum. Mol. Genet. (2005) [Pubmed]
  16. DelGEF, an RCC1-related protein encoded by a gene on chromosome 11p14 critical for two forms of hereditary deafness. Uhlmann, J., Wiemann, S., Ponstingl, H. FEBS Lett. (1999) [Pubmed]
  17. Twister mutant mice are defective for otogelin, a component specific to inner ear acellular membranes. Simmler, M.C., Zwaenepoel, I., Verpy, E., Guillaud, L., Elbaz, C., Petit, C., Panthier, J.J. Mamm. Genome (2000) [Pubmed]
  18. Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain Protein AIE-75. Ishikawa, S., Kobayashi, I., Hamada, J., Tada, M., Hirai, A., Furuuchi, K., Takahashi, Y., Ba, Y., Moriuchi, T. Gene (2001) [Pubmed]
  19. Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis. Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. Hum. Mutat. (2001) [Pubmed]
  20. A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome. Kalay, E., de Brouwer, A.P., Caylan, R., Nabuurs, S.B., Wollnik, B., Karaguzel, A., Heister, J.G., Erdol, H., Cremers, F.P., Cremers, C.W., Brunner, H.G., Kremer, H. J. Mol. Med. (2005) [Pubmed]
  21. Two families from New England with usher syndrome type IC with distinct haplotypes. DeAngelis, M.M., McGee, T.L., Keats, B.J., Slim, R., Berson, E.L., Dryja, T.P. Am. J. Ophthalmol. (2001) [Pubmed]
  22. The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK. Blaydon, D.C., Mueller, R.F., Hutchin, T.P., Leroy, B.P., Bhattacharya, S.S., Bird, A.C., Malcolm, S., Bitner-Glindzicz, M. Clin. Genet. (2003) [Pubmed]
  23. Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues. Johnston, A.M., Naselli, G., Niwa, H., Brodnicki, T., Harrison, L.C., Góñez, L.J. Genes Cells (2004) [Pubmed]
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