Affinage

USH1C

Harmonin · UniProt Q9Y6N9

Length
552 aa
Mass
62.2 kDa
Annotated
2026-06-10
50 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USH1C encodes harmonin, a multi-PDZ-domain scaffold protein that organizes the Usher syndrome (USH) interactome in inner ear hair cells and retinal cells, and its mutation causes Usher syndrome type 1C (PMID:10973247). Harmonin engages cadherin 23 in a multidentate manner — its N-terminal domain and PDZ1 supramodule bind an internal cytoplasmic peptide of CDH23 with high affinity while PDZ2 binds the CDH23 C-terminal tail — and these non-synergizing sites instead drive formation of polymeric CDH23/harmonin complexes that anchor stereocilia tip links (PMID:19297620, PMID:20639393, PMID:22879593). Within the upper tip-link density, the F-actin-bundling harmonin-b isoform links CDH23 to the stereociliary actin core and limits the speed and extent of mechanoelectrical transduction adaptation; loss of this localization reduces hair-bundle mechanosensitivity (PMID:12485990, PMID:19447093, PMID:19756723). Harmonin nucleates a broader USH protein network, binding myosin VIIa, SANS (USH1G), PCDH15 (USH1F), and the USH2 proteins USH2A and VLGR1, and is required for correct subcellular positioning of PCDH15 and SANS in hair cells (PMID:12485990, PMID:12588794, PMID:16301216, PMID:15928608, PMID:21156003); the MYO7A/USH1C/SANS tripartite complex assembles through multivalent interactions that undergo liquid-liquid phase separation, a process disrupted by USH disease mutations (PMID:31644917). At the inner hair cell ribbon synapse harmonin associates with presynaptic Cav1.3 Ca²⁺ channels, limiting channel availability via a ubiquitin-dependent pathway and enhancing voltage-dependent facilitation to control synchronous exocytosis (PMID:21822269, PMID:23613530). Harmonin also suppresses canonical Wnt/β-catenin signaling through direct interaction with β-catenin (PMID:36846582), and its activity is further tuned by an intramolecular open/closed conformational switch and by redox-dependent (glutathionylation) modification that gates partner binding (PMID:28653419, PMID:30380418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Established that USH1C encodes harmonin, a PDZ-domain protein, and that its mutation causes Usher syndrome type 1C, defining the gene's disease relevance and domain architecture.

    Evidence Subtracted cDNA cloning, RT-PCR expression, and patient mutation identification

    PMID:10973247

    Open questions at the time
    • Molecular function of the scaffold not yet defined
    • Tissue distribution of isoforms only partly resolved
  2. 2002 High

    Showed harmonin is the physical and functional hub of the hair-bundle anchoring unit by demonstrating direct binding to cadherin 23 and myosin VIIa and actin-bundling activity, explaining how it shapes stereocilia.

    Evidence Co-IP, in vitro binding, F-actin bundling assays, and localization in myosin VIIa mutant mice; yeast two-hybrid and pulldown for CDH23 with domain mapping

    PMID:12407180 PMID:12485990

    Open questions at the time
    • Structural basis of the dual CDH23 binding surfaces unresolved at this stage
    • Functional consequence of disrupting the link in vivo not yet tested
  3. 2003 Medium

    Expanded the USH1 network by placing SANS (USH1G) in complex with harmonin and mapping harmonin isoform distribution in photoreceptor compartments, linking ear and retinal roles.

    Evidence Co-transfection/Co-IP and subcellular fractionation with immunolocalization in retina

    PMID:12588794 PMID:14578428

    Open questions at the time
    • SANS interaction rested on a single Co-IP
    • Functional significance of isoform compartmentalization in retina untested
  4. 2005 Medium

    Defined harmonin as the scaffold bridging USH1 and USH2 protein classes by mapping PDZ1 binding to USH2A, VLGR1, and NBC3, and PDZ2 binding to PCDH15.

    Evidence Co-IP, yeast two-hybrid, GST pulldown, and immunolocalization at synaptic terminals

    PMID:15928608 PMID:16301216

    Open questions at the time
    • Interactions characterized in vitro or by localization, not in native complexes
    • In vivo dependence of network assembly on these contacts not established
  5. 2009 High

    Tied harmonin's molecular interactions to mechanotransduction physiology by localizing it to the upper tip-link density and showing harmonin-b limits adaptation, establishing a direct structure-to-function chain.

    Evidence Transgenic mice with harmonin domain mutations, immunolocalization, and electrophysiological transduction-current recordings in Ush1c mutants

    PMID:19447093 PMID:19756723

    Open questions at the time
    • Identity of adaptation motors engaged not fully defined
    • Quantitative contribution of actin vs cadherin binding to adaptation not separated
  6. 2010 High

    Provided the atomic and biophysical basis for tip-link assembly by showing multidentate (NTD + PDZ2) CDH23 binding, ternary CDH23/harmonin/myosin VIIa complex formation, and PI(4,5)P2 binding.

    Evidence X-ray crystallography of harmonin NTD and PDZ2 with CDH23 peptides, SPR, liposome binding, and cell-based co-localization in LLC-PK1 cells

    PMID:19297620 PMID:20505086 PMID:20639393

    Open questions at the time
    • Role of the C-terminal PDZ-binding motif reassigned, leaving its physiological function open
    • Mechanistic contribution of PI(4,5)P2 to adaptation not directly demonstrated in vivo
  7. 2010 Medium

    Resolved how the multiple CDH23 binding sites cooperate, showing they drive polymeric rather than synergistic complexes to build a stable tip-link rootlet.

    Evidence In vitro binding, size-exclusion chromatography, and analytical ultracentrifugation

    PMID:22879593

    Open questions at the time
    • Polymer architecture demonstrated in vitro only
    • Stoichiometry within the native tip-link density unknown
  8. 2011 High

    Demonstrated harmonin is required in vivo for spatial organization of the network and revealed a distinct presynaptic role regulating Cav1.3 channels via ubiquitin-dependent degradation.

    Evidence Immunofluorescence of Pcdh15/Sans in Ush1c knockout cochlea; Co-IP, IHC-synapse localization, and electrophysiology for Cav1.3; zebrafish loss-of-function models

    PMID:21156003 PMID:21757509 PMID:21822269

    Open questions at the time
    • Ubiquitin ligase mediating Cav1.3 turnover not identified
    • Müller-glia-specific synaptic requirement mechanism not fully defined
  9. 2013 High

    Refined the synaptic role by showing harmonin binding to the Cav1.3 C-terminus enhances voltage-dependent facilitation and synchronous exocytosis, with a disease mutant abolishing the effect.

    Evidence Whole-cell patch clamp and capacitance recordings in HEK293T cells and mouse IHCs with dfcr mutant controls

    PMID:23613530

    Open questions at the time
    • Relationship between facilitation and ubiquitin-dependent channel limitation not integrated
    • Structural basis of harmonin-Cav1.3 C-terminus contact unresolved
  10. 2018 Medium

    Identified a redox-dependent gating mechanism for selective USH complex assembly, showing glutathionylation promotes harmonin-SANS binding while Grxcr1 reverses it.

    Evidence In vitro binding with glutathionylated proteins and zebrafish grxcr1 mutant hair-bundle analysis

    PMID:30380418

    Open questions at the time
    • Physiological trigger for glutathionylation in hair cells unknown
    • Selective vs tripartite complex regulation mechanism only partly mapped
  11. 2019 Medium

    Reframed tip-link density assembly as a phase-separation phenomenon, showing MYO7A/USH1C/SANS multivalent interactions drive liquid-liquid phase separation that disease mutations impair.

    Evidence In vitro phase separation assays, condensate imaging in cells, Co-IP, and mutational analysis

    PMID:31644917

    Open questions at the time
    • In vivo demonstration of condensates at native tip-link densities lacking
    • Material properties and regulation of the condensate in hair cells undefined
  12. 2022 Medium

    Provided structural and conformational insight into harmonin regulation, defining a PDZ2/coiled-coil-CDHR2 structure with disease mutations and an intramolecular open/closed conformational switch controlling partner binding.

    Evidence X-ray crystallography with stability assays; NMR, AUC, CD, and SPR for the conformational switch

    PMID:28653419 PMID:35747925

    Open questions at the time
    • Trigger that toggles the conformational switch in cells unknown
    • Coiled-coil dimerization role in phase separation not directly tested
  13. 2023 Medium

    Uncovered a signaling role beyond scaffolding, showing harmonin suppresses canonical Wnt/β-catenin signaling and defining its retinal localization and interactions, with patient-cell rescue linking these to USH1C disease.

    Evidence Co-IP, luciferase Wnt reporters, RNA-seq, and Ataluren/transcript-delivery rescue in patient fibroblasts; retinal immunolocalization and rhodopsin Co-IP

    PMID:35997788 PMID:36846582

    Open questions at the time
    • Connection between Wnt suppression and sensory phenotypes unclear
    • Whether nuclear β-catenin binding occurs in hair cells/photoreceptors in vivo untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How harmonin's distinct activities — tip-link anchoring, phase separation, presynaptic Cav1.3 regulation, redox/conformational gating, and Wnt suppression — are coordinated within a single cell remains unresolved.
  • No unified model integrating mechanotransduction and synaptic roles
  • Upstream signals controlling conformational/redox switching unidentified
  • In vivo phase-separation behavior at tip links not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Partners
CACNA1DCDH23CTNNB1MYO7APCDH15USH1GUSH2AVLGR1
Complex memberships
CDH23/harmonin/myosin VIIa ternary complexUSH interactome (MYO7A/USH1C/SANS tip-link density complex)upper tip-link density

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 (not in the eye for certain isoforms). Some isoforms contain an additional coiled-coil domain and proline/serine-rich region. Splice-site, frameshift, and VNTR mutations in USH1C cause Usher syndrome type 1C. Subtracted mouse cDNA library, RT-PCR expression analysis, mutation identification in patients Nature genetics High 10973247
2002 Harmonin-b is an F-actin-bundling protein that binds directly to cadherin 23 and myosin VIIa, forming a functional unit that anchors cadherin 23 to stereocilia microfilaments and shapes the hair bundle. Harmonin b is absent from disorganized hair bundles of myosin VIIa mutant mice, suggesting myosin VIIa conveys harmonin b along the actin core of developing stereocilia. Co-immunoprecipitation, in vitro binding assays, F-actin bundling assay, immunolocalization in wild-type and myosin VIIa mutant mice The EMBO journal High 12485990
2002 Two PDZ domains in harmonin interact with two complementary binding surfaces in the CDH23 cytoplasmic domain, forming a protein complex. CDH23 and harmonin are co-expressed in stereocilia of hair cells. One CDH23 binding surface is disrupted by sequences from an alternatively spliced exon expressed in the ear but not the retina. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, immunolocalization Proceedings of the National Academy of Sciences of the United States of America High 12407180
2003 SANS (USH1G protein) associates with harmonin via its C-terminal class I PDZ-binding motif, placing SANS in the same USH1 protein network as harmonin, myosin VIIa, and cadherin 23. Co-transfection/co-immunoprecipitation in cell culture Human molecular genetics Medium 12588794
2003 Harmonin isoforms are differentially distributed in photoreceptor cell compartments: harmonin b isoforms are restricted to the light-sensitive outer segment, while harmonin a and c isoforms are more ubiquitously distributed. At photoreceptor synaptic terminals, harmonin a and c co-localize with myosin VIIa and cadherin 23. Western blot of subcellular photoreceptor fractions, immunofluorescence, electron microscopy of retina Investigative ophthalmology & visual science Medium 14578428
2005 Harmonin (USH1C) acts as a scaffold protein that molecularly links USH1 and USH2 proteins: the PDZ1 domain of harmonin interacts with the PDZ-binding motifs at the C-termini of USH2A, VLGR1 (USH2C), and NBC3. These USH2 proteins are co-expressed with harmonin at synaptic terminals of retinal photoreceptors and inner ear hair cells. Co-immunoprecipitation, yeast two-hybrid, immunolocalization Human molecular genetics Medium 16301216
2005 Protocadherin 15 (PCDH15/USH1F) interacts with harmonin PDZ2 domain. In the retina, PCDH15 co-localizes with harmonin at the photoreceptor synaptic terminal and at the base of the outer segment where new disk membranes form. GST pulldown, yeast two-hybrid, immunofluorescence, immunoelectron microscopy Molecular vision Medium 15928608
2006 A novel isoform of DOCK4 (DOCK4-Ex49), a guanine nucleotide exchange factor for Rac GTPase, interacts with harmonin and localizes to hair bundle stereocilia in the inner ear, suggesting a Rac-DOCK4-harmonin signaling pathway regulating actin cytoskeleton organization in stereocilia. Yeast two-hybrid, co-immunoprecipitation, 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 harmonin localization in stereocilia. Mice expressing a harmonin mutant that prevents UTLD formation show reduced sensitivity of hair bundles to mechanical stimulation. Immunolocalization, transgenic mouse with harmonin domain mutations, hair bundle mechanosensitivity recordings Neuron High 19447093
2009 Harmonin-b, located at the upper tip-link insertion point, is required for normal adaptation of mechanoelectrical transduction. In Ush1c mutant mice defective for harmonin-b, step deflections evoke transduction currents with altered speed and extent of adaptation. Harmonin-b acts as an intracellular link that limits adaptation and engages adaptation motors, consistent with its binding to both actin filaments and cadherin 23. Electrophysiological recordings of transduction currents in vestibular and cochlear hair cells of Ush1c (dfcr-2J) mutant mice; modeling based on gating spring theory 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 fragment of the cadherin 23 cytoplasmic domain. The harmonin PDZ2 domain separately binds the cadherin 23 C-terminal tail. This multidentate binding mode (NTD + PDZ2) provides the structural basis for stable tip-link complex assembly. X-ray 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; biochemical binding assays Proceedings of the National Academy of Sciences of the United States of America High 19297620
2010 Cadherin 23, harmonin, and myosin VIIa form a ternary complex. The cadherin 23 cytoplasmic region binds harmonin via the harmonin Nter-PDZ1 supramodule with unusually high affinity (not via the cadherin 23 C-terminal PDZ-binding motif). Cadherin 23 also directly binds myosin VIIa tail. Harmonin, cadherin 23, and myosin VIIa all interact with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) on synthetic liposomes, which may contribute to mechanotransduction adaptation. Surface plasmon resonance, liposome binding assays, immunolocalization in wild-type and cadherin 23 null mutant mice Human molecular genetics High 20639393
2010 When harmonin is co-expressed with CDH23 in LLC-PK1 epithelial cells, a large fraction of harmonin co-localizes with CDH23 in microvilli. The primary interaction between CDH23 and harmonin is between the harmonin N-domain and a 35-residue internal peptide of the CDH23 cytoplasmic tail; the CDH23 C-terminal PDZ-binding motif was not required, and the exon 68 peptide did not modulate harmonin binding levels. Epithelial cell transfection model (LLC-PK1-CL4 cells), co-localization imaging, in vitro protein binding assays The Journal of neuroscience Medium 20505086
2010 In Ush1c knockout mice, loss of harmonin causes mislocalization of Pcdh15 (concentrated apically rather than at the stereocilia base/cuticular plate) and mislocalization of Sans (shifted toward the base of stereocilia), demonstrating that harmonin is required for correct subcellular positioning of Pcdh15 and Sans within hair cells. Immunofluorescence on cochlear sections and whole-mount preparations of Ush1c(-/-) knockout mice International journal of experimental pathology Medium 21156003
2011 Harmonin associates with presynaptic Cav1.3 Ca2+ channels at the mouse inner hair cell synapse and limits channel availability through a ubiquitin-dependent pathway. Co-immunoprecipitation, immunolocalization at IHC synapse, electrophysiology Nature neuroscience High 21822269
2011 Harmonin (ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function. Loss of ush1c function in zebrafish (nonsense mutant and morpholino knockdown) causes specific defects in sensory cell structure, hearing, balance, and visual function from the onset of vision. Zebrafish genetic model (ush1c nonsense mutant and morpholino knockdown), behavioral assays, histological analysis Disease models & mechanisms Medium 21757509
2012 The three harmonin binding sites on cadherin 23 (the NTD-binding motif, the exon68 peptide, and the C-terminal PDZ-binding motif) do not synergize in binding to harmonin but instead facilitate formation of polymeric cadherin 23/harmonin complexes, providing a stable rootlet structure for anchoring tip links of stereocilia. In vitro biochemical binding assays, size exclusion chromatography, analytical ultracentrifugation The Journal of biological chemistry Medium 22879593
2013 Harmonin binding to the distal C-terminus of the Cav1.3 α1 subunit enhances voltage-dependent facilitation (VDF) of Cav1.3 currents in HEK293T cells and in mouse inner hair cells. The dfcr harmonin mutant that does not interact with the Cav1.3 C-terminus does not promote VDF. Harmonin also plays a role in synchronous exocytosis and increases the efficiency of Ca2+ influx for triggering exocytosis in IHCs. Whole-cell patch clamp of transfected HEK293T cells and mouse IHCs, membrane capacitance recordings in dfcr mutant and control IHCs The Journal of physiology High 23613530
2004 The first PDZ domain of harmonin interacts with HARP (harmonin-interacting, ankyrin repeat-containing protein) via the three C-terminal amino acids of HARP. Harmonin and HARP co-localize in pancreatic duct epithelium and in a pancreatic beta-cell line under native conditions, forming a putative scaffolding complex. Yeast two-hybrid, overexpression co-immunoprecipitation, confocal microscopy of native tissue Genes to cells Low 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, and through a flexible PDZ2-PDZ3 linker. This conformational switch affects interaction with cadherin-related 23. Biochemical and biophysical analyses (NMR, analytical ultracentrifugation, circular dichroism, surface plasmon resonance) FEBS letters Medium 28653419
2018 Glutathionylation of USH proteins promotes the physical interaction between Ush1c (harmonin) and Ush1ga (Sans), while Grxcr1 prevents this interaction by acting as a deglutathionylating enzyme. Grxcr1 does not affect the assembly of the Ush1c-Cadherin23-Myosin7aa tripartite complex. This identifies a redox-dependent regulatory mechanism for selective USH protein complex formation. In vitro binding assays with glutathionylated proteins, zebrafish grxcr1 mutant analysis, hair bundle morphology assessment Cell reports Medium 30380418
2019 MYO7A, USH1C (harmonin), and USH1G (SANS) form a tripartite complex that undergoes liquid-liquid phase separation in vitro and in cells, suggesting that stereocilia tip-link densities form via phase separation. Strong multivalent interactions between the three proteins are required. Usher syndrome patient mutations in MYO7A weaken multivalent interactions and impair phase separation of the complex. In vitro phase separation assays, fluorescence microscopy of condensates in cells, Co-IP, mutational analysis Cell reports Medium 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 Usher syndrome patient mutations in PDZ2 affect domain stability and target binding. The coiled-coil domain can form antiparallel dimers, potentially relevant to harmonin behavior during liquid-liquid phase separation at tip-link densities. X-ray crystallography, biochemical stability assays FASEB journal Medium 35747925
2023 Harmonin binds to β-catenin, the key effector of the canonical Wnt (cWnt) signaling pathway, particularly to stabilized acetylated β-catenin in nuclei. Overexpression of USH1C/harmonin significantly reduces cWnt signaling in HEK293T cells, while the USH1C-R31* mutant form does not. USH1C patient-derived fibroblasts show increased cWnt signaling, which is reverted by Ataluren-induced read-through restoring USH1C expression. Co-immunoprecipitation, luciferase reporter assays for cWnt signaling, RNAseq of patient fibroblasts, Ataluren rescue experiment Frontiers in cell and developmental biology Medium 36846582
2023 In human retina, harmonin_a1 is the most abundant USH1C transcript. Harmonin is expressed in Müller glia cells (MGCs) and retinal neurons, localizing to terminal endfeet and apical microvilli of MGCs, presynaptic region of cones, outer segments of rods, and at adhesive junctions between MGCs and photoreceptors in the outer limiting membrane (OLM). Harmonin interacts with OLM molecules in PRCs and MGCs, and with rhodopsin in PRCs. Primary cilia defects in USH1C patient-derived fibroblasts are reverted by delivery of harmonin_a1 transcript. RNA-seq, immunoblotting, immunolocalization, co-immunoprecipitation, gene delivery rescue experiment in patient fibroblasts Human molecular genetics Medium 35997788
2020 A heterozygous USH1C missense variant (p.Gly223Cys) in the carboxylate-binding loop of harmonin PDZ2 causes ~16-fold reduction in affinity for the CDH23 PDZ-binding motif peptide due to a conformational change in the PDZ2 domain, establishing that disruption of harmonin-CDH23 interaction can cause 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 351 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 139 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 85 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 52 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 46 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 34 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
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 31 22879593
2009 Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C. Investigative ophthalmology & visual science 30 19324851
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
2023 Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy. Human molecular genetics 15 35997788
2003 The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK. Clinical genetics 15 12702164
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

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