Affinage

USH1C

Harmonin · UniProt Q9Y6N9

Length
552 aa
Mass
62.2 kDa
Annotated
2026-04-28
50 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Harmonin (USH1C) is a multi-PDZ domain scaffold protein that assembles the Usher syndrome type 1 protein network in inner ear hair cells and retinal photoreceptors, coupling extracellular tip-link cadherins to the intracellular actin cytoskeleton and thereby enabling mechanotransduction and sensory cell integrity. Its NTD-PDZ1 supramodule and PDZ2 domain bind cadherin 23 through a multidentate interaction, while harmonin-b isoforms bundle F-actin to anchor tip links at the upper tip-link density; loss of harmonin-b alters mechanotransduction adaptation speed and extent, and harmonin undergoes liquid–liquid phase separation with MYO7A and SANS to form tip-link density condensates (PMID:19447093, PMID:19756723, PMID:31644917, PMID:19297620). Beyond the hair bundle, harmonin scaffolds Cav1.3 Ca²⁺ channels at inner hair cell presynaptic sites, limiting channel availability via ubiquitin-dependent degradation and enhancing voltage-dependent facilitation and synchronous exocytosis (PMID:21822269, PMID:23613530). Biallelic loss-of-function mutations cause Usher syndrome type 1C (combined deafness and retinitis pigmentosa), while a heterozygous missense variant disrupting the PDZ2–cadherin 23 interaction causes autosomal dominant nonsyndromic hearing loss (PMID:10973247, PMID:31858762).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Identification of USH1C as encoding harmonin, a PDZ-domain protein mutated in Usher syndrome 1C patients and selectively expressed in inner ear hair cells, established the molecular entry point for understanding this deafness–blindness syndrome.

    Evidence Subtracted mouse cDNA library screening, RT-PCR expression analysis, and patient mutation identification

    PMID:10973247

    Open questions at the time
    • Protein function and binding partners unknown
    • Retinal expression and role unclear
  2. 2002 High

    Demonstrating that harmonin-b directly binds cadherin 23 via PDZ domains, bundles F-actin, and requires myosin VIIa for stereociliary transport revealed harmonin as the physical link between tip-link cadherins and the actin cytoskeleton.

    Evidence Co-immunoprecipitation, GST pulldown, F-actin bundling assays, and immunofluorescence in wild-type and myosin VIIa mutant mice

    PMID:12407180 PMID:12485990

    Open questions at the time
    • Stoichiometry of the harmonin–CDH23–actin complex unresolved
    • Functional consequence for mechanotransduction not yet tested
  3. 2005 Medium

    Mapping interactions of harmonin PDZ domains with SANS, PCDH15, and USH2 proteins (USH2A, VLGR1) established harmonin as the central scaffold integrating the entire Usher protein network at stereocilia and synaptic sites.

    Evidence Yeast two-hybrid, co-immunoprecipitation, pulldown assays, and co-localization in inner ear and retina

    PMID:12588794 PMID:15928608 PMID:16301216

    Open questions at the time
    • Most interactions validated only by overexpression; endogenous stoichiometry unknown
    • Functional hierarchy among binding partners unclear
  4. 2009 High

    Crystal structures of harmonin NTD and PDZ2 in complex with cadherin 23 peptides, combined with electrophysiology in harmonin mutant mice, revealed a multidentate binding mode that anchors tip links and showed that harmonin-b limits mechanotransduction adaptation.

    Evidence X-ray crystallography of harmonin–CDH23 complexes, SPR, electrophysiology of hair bundles in Ush1c mutant mice, biophysical modeling

    PMID:19297620 PMID:19447093 PMID:19756723

    Open questions at the time
    • How harmonin transmits force to adaptation motors is not structurally resolved
    • Contribution of each CDH23 binding site to adaptation in vivo untested individually
  5. 2010 High

    Reconstitution of the ternary CDH23–harmonin–MYO7A complex with PI(4,5)P2 binding and demonstration that Ush1c knockout causes mislocalization of PCDH15 and SANS established harmonin as essential for organizing the entire USH1 complex in vivo.

    Evidence SPR, liposome binding, ternary complex reconstitution, immunofluorescence in Ush1c knockout mice

    PMID:20639393 PMID:21156003

    Open questions at the time
    • How PI(4,5)P2 binding contributes to adaptation force in situ is unknown
    • Whether harmonin organizes USH2 proteins in vivo as it does USH1 is untested
  6. 2011 High

    Discovery that harmonin associates with Cav1.3 channels at inner hair cell synapses and limits their availability via ubiquitin-dependent degradation extended harmonin's role from the hair bundle to presynaptic calcium signaling.

    Evidence Co-immunoprecipitation, immunolocalization at IHC synapses, electrophysiology in harmonin mutant mice

    PMID:21822269

    Open questions at the time
    • E3 ligase mediating Cav1.3 ubiquitination not identified
    • Whether harmonin directly recruits the proteasome or an adaptor is unknown
  7. 2013 High

    Showing that harmonin enhances voltage-dependent facilitation and synchronous exocytosis of Cav1.3 channels revealed a dual presynaptic function — gating modulation beyond protein degradation — explaining hearing deficits in harmonin mutants.

    Evidence Patch-clamp electrophysiology in HEK293T cells and mouse IHCs with domain-specific mutant controls

    PMID:23613530

    Open questions at the time
    • Molecular mechanism by which harmonin alters Cav1.3 gating is unresolved
    • Whether this pathway is relevant in photoreceptor synapses is untested
  8. 2017 High

    Identification of an intramolecular open-to-closed conformational switch in harmonin-a1, mediated by its C-terminal PDZ-binding motif folding back onto NTD-PDZ1, provided a regulatory mechanism that gates partner binding.

    Evidence NMR, SPR, circular dichroism, and mutagenesis

    PMID:28653419

    Open questions at the time
    • What signals trigger the conformational switch in vivo is unknown
    • Whether all harmonin isoforms undergo this switch is untested
  9. 2019 High

    Reconstitution of liquid–liquid phase separation by the MYO7A–harmonin–SANS tripartite complex, impaired by USH1 patient mutations, proposed a phase-separation mechanism for tip-link density assembly.

    Evidence In vitro phase separation assay, cell-based condensate formation, biolayer interferometry, and patient mutation analysis

    PMID:31644917

    Open questions at the time
    • Phase separation has not been demonstrated in native hair cells in situ
    • Contribution of CDH23 to phase separation is not addressed
  10. 2020 Medium

    A heterozygous PDZ2 missense variant (G223C) causing dominant nonsyndromic hearing loss, with a 16-fold reduction in CDH23 binding affinity, established that even monoallelic disruption of the harmonin–CDH23 interface is pathogenic.

    Evidence Biolayer interferometry, circular dichroism, exome sequencing with family segregation

    PMID:31858762

    Open questions at the time
    • Only a single family reported; replication in additional kindreds needed
    • Whether this variant also affects retinal function is unknown
  11. 2023 Medium

    Discovery that harmonin binds β-catenin and suppresses canonical Wnt signaling, with patient fibroblasts showing elevated Wnt activity, revealed a signaling pathway role beyond the cytoskeletal scaffold function; concurrently, harmonin was mapped to Müller glia endfeet and photoreceptor outer limiting membrane junctions in human retina.

    Evidence Co-immunoprecipitation, luciferase Wnt reporter, patient fibroblast analysis, RNA-seq, immunofluorescence, and cilia rescue in patient cells

    PMID:35997788 PMID:36846582

    Open questions at the time
    • How Wnt suppression connects to retinal degeneration phenotype is unclear
    • Whether Wnt pathway involvement is relevant in hair cells is untested
    • Mechanism by which harmonin_a1 rescues cilia defects is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the in vivo signals that regulate harmonin's conformational switch, the identity of the E3 ligase mediating harmonin-directed Cav1.3 degradation, whether tip-link density phase separation occurs in native hair cells, and how harmonin's Wnt-suppressive activity relates to retinal pathology.
  • No in vivo evidence for phase separation at tip-link densities
  • E3 ligase for Cav1.3 ubiquitination unidentified
  • Regulatory signals for conformational switch unknown
  • Wnt pathway role not linked to specific retinal cell death mechanism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 3 GO:0005929 cilium 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-9709957 Sensory Perception 4 R-HSA-112316 Neuronal System 2 R-HSA-162582 Signal Transduction 1
Partners
CACNA1DCDH23CTNNB1MYO7APCDH15SANSUSH2A
Complex memberships
Tip-link density complexUSH1 protein complex (CDH23–harmonin–MYO7A–SANS)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 USH1C encodes harmonin, a PDZ domain-containing protein expressed exclusively in inner ear sensory hair cells; isoforms containing additional coiled-coil and proline/serine-rich regions are present in the inner ear but absent from the eye, suggesting isoform-specific tissue function. Subtracted mouse cDNA library, RT-PCR, mutation identification in patients Nature genetics High 10973247
2002 Harmonin-b directly binds cadherin 23 (CDH23) via PDZ domain interactions with the CDH23 cytoplasmic domain; harmonin-b is an F-actin-bundling protein that anchors cadherin 23 to stereocilia microfilaments; harmonin-b also directly interacts with myosin VIIa and requires myosin VIIa for transport along the actin core of developing stereocilia. Co-immunoprecipitation, GST pulldown, F-actin bundling assay, immunofluorescence in wild-type and myosin VIIa mutant mice The EMBO journal High 12485990
2002 Two PDZ domains of harmonin interact with two distinct complementary binding surfaces in the CDH23 cytoplasmic domain; one CDH23 binding surface is disrupted by an alternatively spliced exon expressed in the ear but not the retina, providing a molecular basis for tissue-specific complex assembly. Co-immunoprecipitation, pulldown assays, expression of domain deletion constructs Proceedings of the National Academy of Sciences of the United States of America High 12407180
2003 SANS (USH1G protein) associates with harmonin (USH1C) via harmonin's PDZ domains interacting with the class I PDZ-binding motif at the C-terminus of SANS, placing both proteins in the same USH1 protein network. Co-transfection and co-immunoprecipitation in mammalian cells Human molecular genetics Medium 12588794
2003 Harmonin isoforms are differentially distributed in photoreceptor cell compartments: harmonin-b isoforms localize to the outer segment, while harmonin-a and -c isoforms are more ubiquitous and colocalize with myosin VIIa and cadherin 23 at photoreceptor synaptic terminals, suggesting a USH1 supramolecular complex at photoreceptor synapses. Western blot of subcellular photoreceptor fractions, immunofluorescence and electron microscopy of retina Investigative ophthalmology & visual science Medium 14578428
2005 Harmonin (USH1C) acts as a scaffold integrating USH2 proteins (USH2A, VLGR1/USH2C, NBC3) into the USH1 protein network via interactions between the harmonin PDZ1 domain and the PDZ-binding motifs at the C-termini of these USH2 proteins; these complexes localize at stereocilia and synaptic terminals of hair cells and retinal photoreceptors. Pulldown assays, co-immunoprecipitation, immunofluorescence/co-localization in retina and inner ear Human molecular genetics Medium 16301216
2005 Protocadherin 15 (PCDH15/USH1F) interacts with harmonin PDZ2 domain; both proteins colocalize at the photoreceptor synaptic terminal and at the base of the outer segment, suggesting a role for harmonin-PCDH15 interaction in disk morphogenesis and synaptic organization. GST pulldown, yeast two-hybrid, immunofluorescence and immunoelectron microscopy of rodent retina Molecular vision Medium 15928608
2006 A novel DOCK4 isoform (DOCK4-Ex49), a Rac GEF expressed in brain, eye, and inner ear, binds harmonin in stereocilia of hair cells via yeast two-hybrid interaction, suggesting a Rac-DOCK4-harmonin signaling axis for actin cytoskeleton organization in stereocilia. Yeast two-hybrid, immunostaining of inner ear Journal of molecular biology Low 16464467
2009 Harmonin is a component of the upper tip-link density (UTLD) where CDH23 inserts into the stereociliary membrane; harmonin domains mediating CDH23 and F-actin interactions control its localization, and mice with mutant harmonin lacking UTLD formation show reduced mechanotransduction sensitivity. Immunolocalization, genetic mouse models (harmonin mutants), electrophysiology of hair bundles Neuron High 19447093
2009 Harmonin-b operates as an intracellular link that limits adaptation and engages adaptation motors in mechanotransduction; in Ush1c (dfcr-2J) mutant mice lacking harmonin-b, adaptation speed and extent are altered in both vestibular and cochlear hair cells, consistent with harmonin-b binding both actin filaments and cadherin 23 (tip link component). Electrophysiology of hair bundles in Ush1c mutant mice, biophysical modeling Pflugers Archiv : European journal of physiology High 19756723
2009 The harmonin N-terminal domain (NTD) adopts an autonomously folded domain that specifically binds an internal peptide of the cadherin 23 cytoplasmic domain; the harmonin PDZ2 domain binds the cadherin 23 C-terminal tail; this multidentate binding mode provides the structural and biochemical basis for stable tip-link complex assembly. Crystal structures of harmonin N-domain alone and in complex with cadherin 23 internal peptide; crystal structure of harmonin PDZ2 in complex with cadherin 23 C-terminal tail Proceedings of the National Academy of Sciences of the United States of America High 19297620
2010 Cadherin 23 cytoplasmic regions directly interact with harmonin with unusually high affinity via the harmonin Nter-PDZ1 supramodule; cadherin 23 directly binds the tail of myosin VIIa; cadherin 23, harmonin, and myosin VIIa form a ternary complex; all three proteins interact with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) on synthetic liposomes, potentially contributing to adaptation of mechanotransduction. Surface plasmon resonance, reconstitution of ternary complex, liposome binding assay, immunofluorescence in wild-type and cadherin 23 null mutant mice Human molecular genetics High 20639393
2010 Using an epithelial cell model (LLC-PK1-CL4 cells), harmonin colocalizes with cadherin 23 in microvilli upon co-expression; the primary interaction is between the harmonin N-domain and a 35-residue internal peptide in the CDH23 cytoplasmic tail, not requiring the CDH23 C-terminal PDZ-binding motif, and is exon 68-independent. Epithelial cell transfection model, in vitro protein binding assays, fluorescence microscopy The Journal of neuroscience Medium 20505086
2010 In Ush1c knockout mice, absence of harmonin causes mislocalization of Pcdh15 (concentrated in the apical region rather than at the base of stereocilia and cuticular plate) and mislocalization of Sans (shifted toward the base of stereocilia), demonstrating that harmonin is required for correct subcellular positioning of other USH1 network components. Immunofluorescence in Ush1c-/- knockout mouse cochlear sections and whole mounts International journal of experimental pathology Medium 21156003
2011 Harmonin forms a presynaptic association with Cav1.3 Ca2+ channels at the inner hair cell synapse and limits Cav1.3 channel availability through a ubiquitin-dependent proteasomal degradation pathway. Co-immunoprecipitation, immunolocalization at IHC synapse, electrophysiology in harmonin mutant mice Nature neuroscience High 21822269
2011 Harmonin is required in zebrafish Müller glial cells for photoreceptor synaptic development and function; morpholino knockdown and nonsense mutant zebrafish with loss of ush1c show early-onset visual and hearing deficits with structural defects in sensory cells, implicating Müller glia in retinal USH1C pathology. Zebrafish mutant and morpholino knockdown, behavioral assays, histological analysis Disease models & mechanisms Medium 21757509
2012 Cadherin 23 forms polymeric complexes with harmonin through three binding sites (NTD-binding motif, exon68 peptide, and C-terminal PDZ-binding motif); the exon68 peptide promotes polymer formation via harmonin NTD binding or self-dimerization, generating a large macromolecular assembly proposed to form the stable rootlet structure anchoring tip links. In vitro biochemical reconstitution, size-exclusion chromatography, pulldown assays The Journal of biological chemistry Medium 22879593
2013 Harmonin binding to the Cav1.3 α1 subunit distal C-terminus (dCT) enhances voltage-dependent facilitation (VDF) of Cav1.3 currents in HEK293T cells and in mouse inner hair cells; harmonin also promotes synchronous exocytosis and increases the efficiency of Ca2+ influx for triggering exocytosis, revealing a multifaceted presynaptic role. Patch-clamp electrophysiology in HEK293T cells and mouse IHCs, membrane capacitance recordings, dfcr mutant harmonin that cannot bind Cav1.3 dCT as control The Journal of physiology High 23613530
2004 Harmonin PDZ1 domain interacts with a novel ankyrin repeat- and SAM domain-containing protein, HARP, via HARP's three C-terminal amino acids (PDZ-binding motif); native harmonin and HARP colocalize in pancreatic duct epithelium, suggesting a scaffolding complex function in epithelial tissues beyond the inner ear. Yeast two-hybrid, co-immunoprecipitation in mammalian over-expression system, confocal colocalization of native proteins Genes to cells : devoted to molecular & cellular mechanisms Medium 15461667
2017 Harmonin-a1 can switch between open and closed conformations through intramolecular binding of its C-terminal PDZ-binding motif to its N-terminal NTD-PDZ1 supramodule, mediated by a flexible PDZ2-PDZ3 linker; this conformational switch affects binding to cadherin-related 23. Biochemical and biophysical analyses (NMR, SPR, circular dichroism), mutagenesis FEBS letters High 28653419
2018 Glutathionylation of USH1C (harmonin) and USH1G (Sans) promotes their protein-protein interaction; GRXCR1, a deglutathionylating enzyme, prevents this interaction to regulate hair bundle development; this glutathionylation-dependent regulation of the harmonin-Sans complex is distinct from the harmonin-CDH23-MYO7A complex, which is unaffected by GRXCR1. In vitro glutathionylation assays, yeast two-hybrid, zebrafish grxcr1 mutants with hair bundle morphological readout Cell reports Medium 30380418
2019 Myosin VIIA (MYO7A), harmonin (USH1C), and USH1G (SANS) form a tripartite complex that undergoes liquid-liquid phase separation in vitro and in cells to form dense condensates; phase separation requires strong multivalent interactions between the three proteins; USH1-patient MYO7A mutations weaken these interactions and impair phase separation, suggesting tip-link densities form via phase separation. In vitro phase separation assay, cell-based condensate formation, biolayer interferometry/binding assays, USH patient mutation analysis Cell reports High 31644917
2022 Crystal structure of harmonin PDZ2 and coiled-coil domains in complex with the tail of cadherin-related family member 2 (CDHR2) reveals that USH patient mutations in harmonin PDZ2 affect domain stability and target binding; the coiled-coil domain can form antiparallel dimers, potentially relevant to liquid-liquid phase separation at tip-link densities. X-ray crystallography, biochemical stability analysis of patient mutations FASEB journal High 35747925
2023 Harmonin binds to β-catenin and to stabilized acetylated β-catenin in nuclei; overexpression of harmonin significantly reduces canonical Wnt signaling in HEK293T cells, while a USH1C-R31* nonsense mutant does not; USH1C patient-derived fibroblasts show increased canonical Wnt signaling, establishing harmonin as a suppressor of the cWnt/β-catenin pathway. Co-immunoprecipitation, luciferase Wnt reporter assay, patient-derived fibroblast analysis, RNAseq Frontiers in cell and developmental biology Medium 36846582
2023 In human retina, harmonin_a1 is the most abundant transcript isoform; harmonin is expressed in Müller glia cells (MGCs) and retinal neurons and localizes to MGC terminal endfeet and apical microvilli, cone pedicles, rod outer segments, and adhesive junctions (outer limiting membrane) between MGCs and photoreceptors; harmonin interacts with OLM molecules and with rhodopsin in photoreceptors; delivery of harmonin_a1 reverts primary cilia defects in USH1C patient-derived fibroblasts. RNA-seq, immunoblotting, immunofluorescence, co-immunoprecipitation, gene delivery rescue of cilia defects in patient fibroblasts Human molecular genetics Medium 35997788
2020 A heterozygous missense variant (p.Gly223Cys) in the harmonin PDZ2 carboxylate-binding loop causes ~16-fold reduction in affinity for the cadherin 23 PDZ-binding motif and induces a conformational change in PDZ2, establishing that disruption of the harmonin-CDH23 PDZ2 interaction causes autosomal dominant nonsyndromic hearing loss. Biolayer interferometry, circular dichroism, exome sequencing with segregation analysis Annals of laboratory medicine Medium 31858762

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. Nature genetics 357 10973247
2002 Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle. The EMBO journal 350 12485990
2003 Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. Human molecular genetics 228 12588794
2002 The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions. Proceedings of the National Academy of Sciences of the United States of America 191 12407180
2005 Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Human molecular genetics 143 16301216
2009 Harmonin mutations cause mechanotransduction defects in cochlear hair cells. Neuron 138 19447093
2003 Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene. Human molecular genetics 120 14519688
2002 Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness. Human genetics 92 12136232
2010 Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, form a ternary complex and interact with membrane phospholipids. Human molecular genetics 83 20639393
2012 A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation. EMBO molecular medicine 82 23027640
2005 Photoreceptor expression of the Usher syndrome type 1 protein protocadherin 15 (USH1F) and its interaction with the scaffold protein harmonin (USH1C). Molecular vision 76 15928608
2009 Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells. Pflugers Archiv : European journal of physiology 72 19756723
2003 Differential distribution of harmonin isoforms and their possible role in Usher-1 protein complexes in mammalian photoreceptor cells. Investigative ophthalmology & visual science 70 14578428
2011 Harmonin inhibits presynaptic Cav1.3 Ca²⁺ channels in mouse inner hair cells. Nature neuroscience 68 21822269
2009 Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23. Proceedings of the National Academy of Sciences of the United States of America 65 19297620
2011 Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function. Disease models & mechanisms 51 21757509
2010 Deafness and retinal degeneration in a novel USH1C knock-in mouse model. Developmental neurobiology 51 20095043
2013 Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome. PloS one 48 24250806
2010 Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina. Investigative ophthalmology & visual science 45 20671281
2007 Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1C gene provides the first genetic link with the Acadian population. Genome biology 40 17407589
1999 Isoforms of the human PDZ-73 protein exhibit differential tissue expression. Biochimica et biophysica acta 38 10209257
2001 Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis. Human mutation 35 11139240
2019 Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation. Cell reports 33 31644917
2010 Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 20505086
2013 Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells. The Journal of physiology 31 23613530
2013 The C-terminal extension of human RTEL1, mutated in Hoyeraal-Hreidarsson syndrome, contains harmonin-N-like domains. Proteins 31 24130156
2009 Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C. Investigative ophthalmology & visual science 30 19324851
2012 Large protein assemblies formed by multivalent interactions between cadherin23 and harmonin suggest a stable anchorage structure at the tip link of stereocilia. The Journal of biological chemistry 29 22879593
2012 Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss. PloS one 26 23251578
2006 An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C). Journal of molecular biology 26 16464467
2004 The USH1C 216G-->A splice-site mutation results in a 35-base-pair deletion. Human genetics 25 15578223
2011 Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss. Retina (Philadelphia, Pa.) 22 21487335
2004 Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues. Genes to cells : devoted to molecular & cellular mechanisms 19 15461667
2003 USH1C: a rare cause of USH1 in a non-Acadian population and a founder effect of the Acadian allele. Clinical genetics 17 12630964
2003 The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK. Clinical genetics 15 12702164
2023 Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy. Human molecular genetics 14 35997788
2018 Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins. Cell reports 13 30380418
2001 The USH1C 216G-->A mutation and the 9-repeat VNTR(t,t) allele are in complete linkage disequilibrium in the Acadian population. Human genetics 13 11810303
2023 The Usher syndrome 1C protein harmonin regulates canonical Wnt signaling. Frontiers in cell and developmental biology 11 36846582
2010 Analysis of subcellular localization of Myo7a, Pcdh15 and Sans in Ush1c knockout mice. International journal of experimental pathology 10 21156003
2017 Conformational switch of harmonin, a submembrane scaffold protein of the hair cell mechanoelectrical transduction machinery. FEBS letters 9 28653419
2024 Harmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sites. Nucleic acids research 7 38153196
2021 Structure and Membrane Targeting of the PDZD7 Harmonin Homology Domain (HHD) Associated With Hearing Loss. Frontiers in cell and developmental biology 7 33937240
2022 Structure of the Harmonin PDZ2 and coiled-coil domains in a complex with CDHR2 tail and its implications. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 35747925
2021 Phylogenetic analysis of Harmonin homology domains. BMC bioinformatics 5 33853521
2010 Novel mutations in the USH1C gene in Usher syndrome patients. Molecular vision 5 21203349
2022 Resonance assignment and secondary structure of the tandem harmonin homology domains of human RTEL1. Biomolecular NMR assignments 2 35320499
2020 A Novel Heterozygous Missense Variant (c.667G>T;p.Gly223Cys) in USH1C That Interferes With Cadherin-Related 23 and Harmonin Interaction Causes Autosomal Dominant Nonsyndromic Hearing Loss. Annals of laboratory medicine 2 31858762
2020 Identification and computational analysis of USH1C, and SLC26A4 variants in Pakistani families with prelingual hearing loss. Molecular biology reports 2 33231815
2004 Structure, diversity, and evolution of the 45-bp VNTR in intron 5 of the USH1C gene. Genomics 1 14962669