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FLASH GENE
Symbol CDH23 contributors: mct/pgu - updated : 07-06-2017
HGNC name cadherin related 23
HGNC id 13733
DNA
TYPE functioning gene
SPECIAL FEATURE gene in gene, opposite orientation
text a nested gene (FLJ00041) in intron 3, in opposite orientation
STRUCTURE 419.01 kb     70 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map see USH1D
regionally located tightly linked (tail to tail) with PSAP
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 splicing 2684 58.3 530 retina specific 2001 11750125
  • also called variant 2/isoform 2
  • truncated form
  • 70 - 11134 369 3354 - 2001 11750125
    also called variant 1/isoform 1
    - - 1739 - 216 - 2001 11750125
    also called variant 9/isoform 9
    - - 1844 - 251 - 2001 11750125
    also called variant 8/isoform 8
    - - 4236 - 1079 - 2001 11750125
    also called variant 7/isoform 7
    - - 4341 - 1114 - 2001 11750125
    also called variant 6/isoform 6
    11 - 1746 - 406 - 2001 11750125
    also called variant 5/isoform 5
    26 - 3967 - 1061 - 2001 11750125
    also called variant 4/isoform 4
    32 - 4843 - 1831 - 2001 11750125
    also called variant 3/isoform 3
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/EquilibriumearinnercochleaCorti  Homo sapiens
    Visualeyeretina   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumcochlea cell Homo sapiens
    Hearing / Equilibriumstereocilia
    Visualcone photoreceptor
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text hair cell differentiation
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus contains polar amino acids that bind Ca2+ (Elledge 2010)
  • 27 extracellular cadherin repeats containing a C terminal calcium binding motif
  • a single transmembrane segment
  • a unique cytoplasmic tail, predicted signal peptide with two putative binding sites for PDZ domains
  • HOMOLOGY
    interspecies homolog to Drosophila FAT gene
    homolog to murine Cdh23
    Homologene
    FAMILY
  • cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane
    text transmembrane protein localized near the tips of hair cell stereocilia
    basic FUNCTION
  • playing a role in the maintenance of hair bundles during development, also maintenance of the organization of the stereocilia bundles and in adult hair cells to form kinocilia links and tip links
  • may be regulating photoreceptors development or function
  • CDH23, PCDH15 and ADGRV1 have been implicated in the development of cochlear hair cell stereocilia, while CLRN1 has been suggested to also play a role in synaptogenesis
  • the role played by CDH23 in retinal function is likely performed by either a different gene or an unidentified CDH23 splice variant in the retina
  • 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
  • because the USH1G and CDH23 proteins form a complex in the stereocilia, the interaction between these proteins may play key roles in the maintenance of stereocilia and the prevention of early-onset progressive hearing loss (PHL)
  • is an adhesive protein important for hearing and vision
  • reported to play a role in tumor progression through regulating cell-cell adhesion
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/hearing , sensory transduction/vision
    a component
  • complexing with USH1C and MYO1C (to regulate the activity of mechanically gated ion channels in hair cells
  • with harmonin (USH1C) and myosin VIIa can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links
  • 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
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ion Ca2+
  • protein
  • homophilic, calcium dependent, cell cell interactions
  • interacting by its C terminus with the cytoskeleton via beta-catenin
  • interacts via an internal PDZ-binding site with the PDZ1 domain of the stereociliary protein harmonin, and potentially via a weaker binding of its C terminus with harmonin PDZ2 domain
  • EHD4 is a novel CDH23-interacting protein that could regulate CDH23 trafficking/localization in a calcium-sensitive manner)
  • interacting with USH1C (to connect stereocilia into a bundle)
  • interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links, in sensory hair cells
  • CDH23 and PCDH15 interact to form tip links, which gate mechanotransduction channels in hair cells of the inner ear
  • directly binds to the tail of myosin VIIa (MYO7A)
  • with harmonin and myosin VIIa bind to phosphorylated forms of phosphatidylinositol including phosphatidylinositol 4,5-bisphosphate
  • CNGA3 interacts with stereocilia tip-link CDH23 + exon 68 or alternatively with MYO7A, two proteins required for hair cell mechanotransduction
  • CDH23, PCDH15 bind tip-to-tip in a "handshake" mode that involves the EC1 and EC2 repeats ofCDH23, PCDH15
  • interaction between CDH23 and CAMSAP3/Marshalin plays a vital role in hearing and vision, suggesting that CDH23-C is a CAMSAP3/Marshalin-binding protein that can modify MT networks indirectly through its interaction with CAMSAP3/Marshalin
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DFNB12 , USH1D
    related resource Hereditary Hearing Loss Homepage
    Susceptibility
  • to age-related hearing-loss
  • to both familial and sporadic pituitary adenoma (PA)
  • to semicircular canal dehiscence (SCD)
  • to noise-induced hearing loss (NIHL)
  • Variant & Polymorphism SNP
  • in exon 7, significant association with age-related hearing-loss
  • significantly increased risk of PAs in subjects with CDH23 mutations
  • children with a CDH23 pathogenic variants are at significantly increased risk of having SCD and this may be a contributing factor to the vestibular dysfunction in Usher syndrome type 1D patient population
  • genetic variant may modify the susceptibility to NIHL
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • waltzer mouse, with stereocilia disorganization
  • salsa mice, which suffer from hearing loss due to a Cdh23 missense mutation modeling DFNB12 with hair cell development unaffected (salsa mutation affects interactions of CDH23 and PCDH15, even though the mutation affects an amino acid outside the ligand-binding domain in EC1)