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Symbol USH1C contributors: shn/npt/pgu - updated : 07-12-2017
HGNC name USH1 protein network component harmonin
HGNC id 12597
Corresponding disease
USH1C Usher syndrome, type IC
Location 11p15.1      Physical location : 17.515.442 - 17.565.963
Synonym name
  • harmonin
  • autoimmune enteropathy related antigen 75kDa
  • Usher syndrome 1C (autosomal recessive severe/harmonin,PDZ containing protein,harmonin)
  • renal carcinoma antigen NY-REN-3
  • antigen NY-CO-38/NY-CO-37
  • protein PDZ-73
  • Synonym symbol(s) PDZ73, harmonin, NY-CO-37, NY-CO-38, PDZ-73, AIE-75, DFNB18, PDZ-45, ush1cpst, PDZ-73, PDZD7C
    TYPE functioning gene
    SPECIAL FEATURE overlapping, gene in gene
    text overlapping with DNFB18
    STRUCTURE 50.52 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   other
    text structure VNTR in intron 5
    MAPPING cloned Y linked N status provisional
    Map pter - D11S921 - D11S902 - USH1C USH1C - D11S4138 - D11S4130 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 splicing 2237 73 552 cytoplasmic reactivity in epithelial cells of the small intestine, colon and kidney tubules - stereocilia of hair cells, and in the retina within the synapse of photoreceptor cell layer 2010 20142502
  • harmonin a
  • an additional PDZ domain at its C terminus
  • 27 splicing 3246 - 899 stereocilia of hair cells, and in the retina within synapse of the photoreceptor cell layer 2010 20142502
  • harmonin b
  • an additional PDZ domain at its C terminus
  • also contains a Pro, Ser, Th-rich sequence (PST) domain preceding the C-terminal PDZ domain that is known to be responsible for binding to F-actin
  • 20 - 2180 - 533 - 2010 20142502
  • harmonin c
  • contains an N-terminal globular domain , two PDZ domains, and one or two coiled-coil regions
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestinejejunumcrypt of Lieberkuhn 
     intestinelarge intestinecolon  
    Reproductivemale systemtestis   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumcochlea cell
    Hearing / Equilibriumstereocilia
    Visualcone photoreceptor
    cell lineage
    cell lines
    at STAGE
  • N-terminal domain and the first PDZ domain are tethered by a small-domain C-terminal to PDZ1 to form a structural and functional supramodule responsible for binding to USH1G, and PDZ2 domain binds to the cytoplasmic portion of cadherin 23
  • three conserved domains PSD/DLG/ZO1 (PDZ) domains
  • one or two coiled-coil region(s)
  • a putative PEST protein degradation motif
  • one C terminal PBI domain (PDZ- binding interface)
    interspecies ortholog to Ush1c, Mus musculus
    ortholog to Ush1c, Rattus norvegicus
    ortholog to ush1c, Danio rerio
    ortholog to USH1C, Pan troglodytes
    CATEGORY antigen
    SUBCELLULAR LOCALIZATION     plasma membrane
    text USH2A, VLGR1 and NBC3 are co-expressed with the USH1-protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells
    basic FUNCTION
  • autoantigen involved in intracellular signaling cascade
  • cooperates with Myosin VIIaand cadherin 23 to shape the sensory hair cell bundle
  • essential to ensure the cohesion of the stereocilia
  • MYO7A, USH1G, and USH1C form the core components of the stereocilia upper tip-link density molecular complex
  • USH1G, MYO7A, USH1C, CDH23, PCDH15 form an adhesion belt around the basolateral region of the photoreceptor outer segment, and defects in this structure cause the retinal degeneration in USH1 patients
  • in contrast to other actin-bundling proteins such as ESPN, USH1C or EPS8, PLS1 is dispensable for the initial formation of stereocilia
  • ANKS4B interacts with USH1C and MYO7B, which link protocadherins to the actin cytoskeleton, and ANKS4B and USH1C also bind to the MYO7B cargo-binding tail at distinct sites
  • while PDZ protein USH1C is not involved, its paralogous USH2 proteins, PDZD7 and WHRN, function synergistically in USH2 complex assembly in cochlear hair cells
    PHYSIOLOGICAL PROCESS immunity/defense
    signaling sensory transduction/hearing , sensory transduction/vision
    possible Rac-DOCK4-ABP harmonin-activated signaling pathway in regulating actin cytoskeleton organization in stereocilia
    a component
  • complexing with CDH23, MYO7A, USH1C (with CDH23 and myosin VIIa can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links)
  • USH1C, ANKS4B, and MYO7B form a stable ternary complex for anchoring microvilli tip-link cadherins
  • harmonin/Sans (USH1C/USH1G)complex may serve as a platform to interact with many other proteins related to the development of hearing and visual cells via a number of other unoccupied domains in the complex
  • MYO7A, USH1G, and the upper tip-link density protein USH1C form a tripartite complex and that each protein is capable of interacting with one another independently
  • polymeric CDH23/USH1C complex formed beneath the upper tip link membranes may serve as part of the stable rootlet structure for anchoring the tip links of stereocilia
    small molecule
  • Usher syndrome 1C binding protein 1, USHBP1 (
  • Usher syndrome proteins cadherin 23, CDH23 (
  • Usher syndrome type I G, USH1G (
  • harmonin-interacting ankyrin repeat-containing protein, Harp (
  • myosin VIIA, MYO7A
  • usher syndrome type-2A protein, USH2A; G protein-coupled receptor 98, GPR98 (also known as VLGR1 or USH2C) and solute carrier family 4, sodium bicarbonate cotransporter, member 8, SLC4A8 (otherwise known as NBC3)
  • protocadherin-related 15, PCDH15
  • dedicator of cytokinesis 4, DOCK4
  • binding DOCK4, an unconventional guanine exchange factor for the Rho family of guanosine triphosphatases (Rho GEF GTPases)
  • with CDH23 and myosin VIIa bind to phosphorylated forms of phosphatidylinositol including phosphatidylinositol 4,5-bisphosphate
  • multifaceted presynaptic role of USH1C in cochlear inner hair cells (IHCs) in regulating CACNA1D channels and exocytosis
  • ANKS4B interacts with USH1C and MYO7B, which link protocadherins to the actin cytoskeleton
  • cell & other
    corresponding disease(s) USH1C , DFNB18
    related resource Genetics hearing impairment
    Retinal Information Network
    Variant & Polymorphism
    Candidate gene
    Therapy target
    Commercial aminoglycosides and NB30 induced significant read-through of the USH1C-p.R31X nonsense mutation with ignificantly reduced toxicity and good biocompatibility
  • Ush1c mutant mice congenital exhibit deafness and severe balance deficits due to inner ear dysfunction, stereocilia of cochlear hair cells are disorganized and splayed (
  • deaf circler mice (dfcr), which carry a 12.8kb intragenic deletion of Ush1c gene that eliminates the second and third PDZ domain, have a normal retinal structure, synaptic ultrastructure and ERGs (William et al, 2009)