Gene Symbol: harmonin
Description: USH1 protein network component harmonin
Alias: 2010016F01Rik, harmonin, harmonin, PDZ domain-containing protein, Usher syndrome 1C homolog, usher syndrome type-1C protein homolog
Species: mouse
Products:     harmonin

Top Publications

  1. Boëda B, El Amraoui A, Bahloul A, Goodyear R, Daviet L, Blanchard S, et al. Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle. EMBO J. 2002;21:6689-99 pubmed
    ..Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23...
  2. Lentz J, Pan F, Ng S, Deininger P, Keats B. Ush1c216A knock-in mouse survives Katrina. Mutat Res. 2007;616:139-44 pubmed
    ..site mutation (216G-->A) in exon 3 of the USH1C gene on chromosome 11p, which encodes a PDZ-domain protein, harmonin, was found in Acadian Usher type IC patients in south Louisiana...
  3. Bolz H, von Brederlow B, Ramirez A, Bryda E, Kutsche K, Nothwang H, et al. Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat Genet. 2001;27:108-12 pubmed
    ..have been mapped, but only two USH1 genes have been identified: MYO7A for USH1B and the gene encoding harmonin for USH1C...
  4. Lentz J, Gordon W, Farris H, MacDonald G, Cunningham D, Robbins C, et al. Deafness and retinal degeneration in a novel USH1C knock-in mouse model. Dev Neurobiol. 2010;70:253-67 pubmed publisher
    ..This knock-in mouse reproduces the dual sensory loss of human Usher I, providing a novel resource to study the disease mechanism and the development of therapies. ..
  5. Johnson K, Gagnon L, Webb L, Peters L, Hawes N, Chang B, et al. Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene. Hum Mol Genet. 2003;12:3075-86 pubmed
    ..b>Harmonin, the protein encoded by Ush1c, has been shown to bind, by means of its PDZ-domains, with the products of other ..
  6. Siemens J, Kazmierczak P, Reynolds A, Sticker M, Littlewood Evans A, Muller U. The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions. Proc Natl Acad Sci U S A. 2002;99:14946-51 pubmed
    ..They encode the unconventional myosin VIIa, the PDZ-domain protein harmonin, and the putative adhesion receptors cadherin 23 (CDH23) and protocadherin 15 (PCDH15)...
  7. Michalski N, Michel V, Caberlotto E, Lefevre G, van Aken A, Tinevez J, et al. Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells. Pflugers Arch. 2009;459:115-30 pubmed publisher
    We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells...
  8. Verpy E, Leibovici M, Zwaenepoel I, Liu X, Gal A, Salem N, et al. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. Nat Genet. 2000;26:51-5 pubmed
    ..We identified this gene (USH1C), encoding a PDZ-domain-containing protein, harmonin, in a subtracted mouse cDNA library derived from inner ear sensory areas...
  9. Senften M, Schwander M, Kazmierczak P, Lillo C, Shin J, Hasson T, et al. Physical and functional interaction between protocadherin 15 and myosin VIIa in mechanosensory hair cells. J Neurosci. 2006;26:2060-71 pubmed
    ..Together, our findings suggest that PCDH15 and MYO7A cooperate to regulate the development and function of the mechanically sensitive hair bundle. ..

More Information


  1. Grillet N, Xiong W, Reynolds A, Kazmierczak P, Sato T, Lillo C, et al. Harmonin mutations cause mechanotransduction defects in cochlear hair cells. Neuron. 2009;62:375-87 pubmed publisher
    ..Here we show that the PDZ-domain protein harmonin is a component of the upper tip-link density (UTLD), where CDH23 inserts into the stereociliary membrane...
  2. Lefevre G, Michel V, Weil D, Lepelletier L, Bizard E, Wolfrum U, et al. A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development. 2008;135:1427-37 pubmed publisher
    ..Mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15 or sans cause Usher syndrome type I (USH1, characterized by congenital deafness, ..
  3. El Amraoui A, Petit C. Usher I syndrome: unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cells. J Cell Sci. 2005;118:4593-603 pubmed
    Defects in myosin VIIa, the PDZ-domain-containing protein harmonin, cadherin 23 and protocadherin 15 (two cadherins with large extracellular regions), and the putative scaffolding protein Sans underlie five genetic forms of Usher syndrome ..
  4. Weil D, El Amraoui A, Masmoudi S, Mustapha M, Kikkawa Y, Laine S, et al. Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. Hum Mol Genet. 2003;12:463-71 pubmed
    ..We showed, by means of co-transfection experiments, that SANS associates with harmonin, a PDZ domain-containing protein responsible for USH1C...
  5. Reiners J, Reidel B, El Amraoui A, Boëda B, Huber I, Petit C, et al. Differential distribution of harmonin isoforms and their possible role in Usher-1 protein complexes in mammalian photoreceptor cells. Invest Ophthalmol Vis Sci. 2003;44:5006-15 pubmed
    ..Previous studies have shown that the USH1-proteins myosin VIIa, harmonin, and cadherin 23 interact and form a functional network during hair cell differentiation in the inner ear...
  6. Adato A, Michel V, Kikkawa Y, Reiners J, Alagramam K, Weil D, et al. Interactions in the network of Usher syndrome type 1 proteins. Hum Mol Genet. 2005;14:347-56 pubmed
    Defects in myosin VIIa, harmonin (a PDZ domain protein), cadherin 23, protocadherin 15 and sans (a putative scaffolding protein), underlie five forms of Usher syndrome type I (USH1)...
  7. Adato A, Lefevre G, Delprat B, Michel V, Michalski N, Chardenoux S, et al. Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. Hum Mol Genet. 2005;14:3921-32 pubmed
    ..and in vitro binding assays, we establish that the usherin cytodomain can bind to whirlin and harmonin, two PDZ domain-containing proteins that are defective in genetic forms of isolated deafness and USH type I, ..
  8. Caberlotto E, Michel V, Foucher I, Bahloul A, Goodyear R, Pepermans E, et al. Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia. Proc Natl Acad Sci U S A. 2011;108:5825-30 pubmed publisher
    ..Because sans localizes mainly to the tips of short- and middle-row stereocilia in vivo, we conclude that it belongs to a molecular complex at the lower end of the tip-link and plays a critical role in the maintenance of this link. ..
  9. Cosgrove D, Zallocchi M. Usher protein functions in hair cells and photoreceptors. Int J Biochem Cell Biol. 2014;46:80-9 pubmed publisher
  10. Williams D, Aleman T, Lillo C, Lopes V, Hughes L, Stone E, et al. Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C. Invest Ophthalmol Vis Sci. 2009;50:3881-9 pubmed publisher
    To investigate the expression of harmonin in the mouse retina, test for ultrastructural and physiological mutant phenotypes in the retina of an Ush1c mutant mouse, and define in detail the retinal phenotype in human USH1C...
  11. Xiong W, Grillet N, Elledge H, Wagner T, Zhao B, Johnson K, et al. TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells. Cell. 2012;151:1283-95 pubmed publisher
    ..We conclude that TMHS is an integral component of the hair cell's mechanotransduction machinery that functionally couples PCDH15 to the transduction channel. ..
  12. Crawley S, Shifrin D, Grega Larson N, McConnell R, Benesh A, Mao S, et al. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell. 2014;157:433-446 pubmed publisher
    ..The cytoplasmic domains of microvillar protocadherins interact with the scaffolding protein, harmonin, and myosin-7b, which promote localization to microvillar tips...
  13. Jansen F, Kalbe B, Scholz P, Mikosz M, Wunderlich K, Kurtenbach S, et al. Impact of the Usher syndrome on olfaction. Hum Mol Genet. 2016;25:524-33 pubmed publisher
    ..In summary, this study provides novel insights into the presence and purpose of the Usher proteins in olfactory signal transduction. ..
  14. Johnston A, Naselli G, Niwa H, Brodnicki T, Harrison L, Gonez L. Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues. Genes Cells. 2004;9:967-82 pubmed
    Mutations in the triple PDZ domain-containing protein harmonin have been identified as the cause of Usher deafness syndrome type 1C. Independently, we identified harmonin in a screen for genes expressed in pancreatic beta cells...
  15. Maerker T, Van Wijk E, Overlack N, Kersten F, McGee J, Goldmann T, et al. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet. 2008;17:71-86 pubmed
    ..The scaffold protein harmonin (USH1C) was shown to integrate all identified USH1 and USH2 molecules into protein networks...
  16. Zheng Q, Scarborough J, Zheng Y, Yu H, Choi D, Gillespie P. Digenic inheritance of deafness caused by 8J allele of myosin-VIIA and mutations in other Usher I genes. Hum Mol Genet. 2012;21:2588-98 pubmed publisher
    ..MYO7A, USH1G (Sans) and CDH23 form the upper tip-link complex in adult mice, likely in combination with USH1C (harmonin). MYO7A, USH1G and PCDH15 may form another complex in stereocilia...
  17. Etournay R, Lepelletier L, Boutet de Monvel J, Michel V, Cayet N, Leibovici M, et al. Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape. Development. 2010;137:1373-83 pubmed publisher
    ..We propose that this remodeling contributes to optimize the mechanical coupling between the basal and apical poles of mature OHCs. ..
  18. Lelli A, Michel V, Boutet de Monvel J, Cortese M, Bosch Grau M, Aghaie A, et al. Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth. J Cell Biol. 2016;212:231-44 pubmed publisher
  19. Tian C, Liu X, Han F, Yu H, Longo Guess C, Yang B, et al. Ush1c gene expression levels in the ear and eye suggest different roles for Ush1c in neurosensory organs in a new Ush1c knockout mouse. Brain Res. 2010;1328:57-70 pubmed publisher
    ..of the inner ear and in photoreceptor cells of the retina via binding to PDZ domains in the scaffold protein harmonin encoded by the Ush1c gene in mice and humans...
  20. Zou J, Chen Q, Almishaal A, Mathur P, Zheng T, Tian C, et al. The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells. Hum Mol Genet. 2017;26:624-636 pubmed publisher
    ..The four USH2 proteins also interact in vitro with USH1 proteins including myosin VIIa, USH1G (SANS), CIB2 and harmonin. However, it is unclear whether the interactions between USH1 and USH2 proteins occur in vivo and whether USH1 ..
  21. Grimsley Myers C, Sipe C, Géléoc G, Lu X. The small GTPase Rac1 regulates auditory hair cell morphogenesis. J Neurosci. 2009;29:15859-69 pubmed publisher
    ..Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle...
  22. Pompeia C, Hurle B, Belyantseva I, Noben Trauth K, Beisel K, Gao J, et al. Gene expression profile of the mouse organ of Corti at the onset of hearing. Genomics. 2004;83:1000-11 pubmed
    ..This resource provides both a view of the profile of gene expression in the OC at the onset of hearing and a tool to identify novel genes of importance in hearing. ..
  23. Yan D, Li F, Hall M, Sage C, Hu W, Giallourakis C, et al. An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C). J Mol Biol. 2006;357:755-64 pubmed
    ..Mutations in the actin bundling and PDZ domain-containing protein harmonin are the causes of Usher syndrome type 1C (USH1C), a syndrome of congenital deafness and progressive blindness, as ..
  24. Gregory F, Bryan K, Pangrsic T, Calin Jageman I, Moser T, Lee A. Harmonin inhibits presynaptic Cav1.3 Ca²? channels in mouse inner hair cells. Nat Neurosci. 2011;14:1109-11 pubmed publisher
    b>Harmonin is a scaffolding protein that is required for normal mechanosensory function in hair cells. We found a presynaptic association of harmonin and Ca(v)1...
  25. Zheng L, Zheng J, Whitlon D, Garcia Anoveros J, Bartles J. Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. J Neurosci. 2010;30:7187-201 pubmed publisher
    ..In cells coexpressing the Cdh23 cytoplasmic binding protein harmonin, a large fraction of harmonin became colocalized with Cdh23 in microvilli...
  26. Goldmann T, Rebibo Sabbah A, Overlack N, Nudelman I, Belakhov V, Baasov T, et al. Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina. Invest Ophthalmol Vis Sci. 2010;51:6671-80 pubmed publisher
    ..Restoration of harmonin functions was monitored in GST pull-downs (scaffold function) and by F-actin bundling analysis in HEK293T cells...
  27. Reiners J, Nagel Wolfrum K, Jürgens K, Märker T, Wolfrum U. Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease. Exp Eye Res. 2006;83:97-119 pubmed
    ..adhesion cadherin proteins, cadherin 23 (USH1D) and protocadherin 15, (USH1F) and the scaffold proteins, harmonin (USH1C) and SANS (USH1G). In addition, two USH2 genes and one USH3A gene have been identified...
  28. Verpy E, Weil D, Leibovici M, Goodyear R, Hamard G, Houdon C, et al. Stereocilin-deficient mice reveal the origin of cochlear waveform distortions. Nature. 2008;456:255-8 pubmed publisher
  29. Gregory F, Pangrsic T, Calin Jageman I, Moser T, Lee A. Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells. J Physiol. 2013;591:3253-69 pubmed publisher
    ..b>Harmonin is a PDZ-domain-containing protein that interacts with the C-terminus of the Cav1.3 ?1 subunit (?11...
  30. Papal S, Cortese M, Legendre K, Sorusch N, Dragavon J, Sahly I, et al. The giant spectrin ?V couples the molecular motors to phototransduction and Usher syndrome type I proteins along their trafficking route. Hum Mol Genet. 2013;22:3773-88 pubmed publisher
    ..We showed that spectrin ?V also associates with two USH1 proteins, sans (USH1G) and harmonin (USH1C)...
  31. Verpy E, Leibovici M, Michalski N, Goodyear R, Houdon C, Weil D, et al. Stereocilin connects outer hair cell stereocilia to one another and to the tectorial membrane. J Comp Neurol. 2011;519:194-210 pubmed publisher
    ..We conclude that stereocilin is essential to the formation of horizontal top connectors. We propose that these links, which maintain the cohesiveness of the mature OHC hair bundle, are required for tip-link turnover. ..
  32. Reiners J, Van Wijk E, Märker T, Zimmermann U, Jürgens K, te Brinke H, et al. Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Hum Mol Genet. 2005;14:3933-43 pubmed
    ..We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network...
  33. Zallocchi M, Sisson J, Cosgrove D. Biochemical characterization of native Usher protein complexes from a vesicular subfraction of tracheal epithelial cells. Biochemistry. 2010;49:1236-47 pubmed publisher
    ..This complex(es) is present primarily in transport vesicles at the apical pole of tracheal epithelial cells, predicting that Usher proteins may be directionally transported as complexes in hair cells and photoreceptors. ..
  34. Yan D, Kamiya K, Ouyang X, Liu X. Analysis of subcellular localization of Myo7a, Pcdh15 and Sans in Ush1c knockout mice. Int J Exp Pathol. 2011;92:66-71 pubmed publisher
    ..To understand further the function of harmonin in the pathogenesis of USH1, we have generated a targeted null mutation Ush1c mouse model...
  35. Lentz J, Jodelka F, Hinrich A, McCaffrey K, Farris H, Spalitta M, et al. Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness. Nat Med. 2013;19:345-50 pubmed publisher
  36. Schneider E, Märker T, Daser A, Frey Mahn G, Beyer V, Farcas R, et al. Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing congenital hearing impairment. Hum Mol Genet. 2009;18:655-66 pubmed publisher
    ..PDZD7 shares sequence homology with the PDZ domain-containing genes, USH1C (harmonin) and DFNB31 (whirlin)...
  37. Reiners J, Märker T, Jürgens K, Reidel B, Wolfrum U. Photoreceptor expression of the Usher syndrome type 1 protein protocadherin 15 (USH1F) and its interaction with the scaffold protein harmonin (USH1C). Mol Vis. 2005;11:347-55 pubmed
    ..proteins, namely myosin VIIa (USH1B), SANS (USH1G), and cadherin 23 (USH1D) interact with the USH1C gene product harmonin. In these protein-protein complexes harmonin acts as the scaffold protein binding these USH1 molecules via its ..
  38. Bahloul A, Michel V, Hardelin J, Nouaille S, Hoos S, Houdusse A, et al. Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, form a ternary complex and interact with membrane phospholipids. Hum Mol Genet. 2010;19:3557-65 pubmed publisher
    ..of the two cadherin-23 isoforms that do or do not contain the exon68-encoded peptide directly interact with harmonin, a submembrane PDZ (post-synaptic density, disc large, zonula occludens) domain-containing protein, with ..