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FLASH GENE
Symbol CDH23 contributors: mct/pgu - updated : 07-06-2017
HGNC name cadherin related 23
HGNC id 13733
Corresponding disease
DFNB12 neurosensory deafness 12
USH1D Usher syndrome type ID
Location 10q22.1      Physical location : 73.156.690 - 73.575.702
Synonym name
  • cadherin-23
  • otocadherin
  • cadherin-like 23
  • Synonym symbol(s) KIAA1812, KIAA1774, CDHR23, DKFZp434P2350, FLJ00233, FLJ36499
    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
    Physical map
    LOC387686 10 LOC387686 H2AFY2 10q22.3 H2A histone family, member Y2 AMID 10q22.2 apoptosis-inducing factor (AIF)-homologous mitochondrion-associated inducer of death MGC34695 10q22.2 hypothetical protein MGC34695 SARA1 10q22.2 SAR1a gene homolog 1 (S. cerevisiae) CALM2P2 10q22.2 calmodulin 2 pseudogene 2 PP 10q22.1-q22.2 pyrophosphatase (inorganic) OT7T022 10q21-q22 neuropeptide FF 1; RFamide-related peptide receptor FLJ10751 10q22.2 hypothetical protein FLJ10751 LOC221017 10q22.2 similar to chromosome 6 open reading frame 182 EIF4EBP2 10q21-q22 eukaryotic translation initiation factor 4E binding protein 2 NODAL 10q21.1-q22.2 nodal homolog (mouse) KIAA1274 10q22.1 nodal homolog (mouse) PRF1 10q22.2 perforin 1 (pore forming protein) ADAMTS14 10q21.3 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 14 C10orf27 10q22.2 chromosome 10 open reading frame 27 LOC338611 10q22.2 similar to 40S ribosomal protein S26 SGPL1 10q22 sphingosine-1-phosphate lyase 1 PCBD 10q22 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1) UNC5B 10q22.2 unc-5 homolog B (C. elegans) SLC29A3 10q22.2 solute carrier family 29 (nucleoside transporters), member 3 CDH23 10q22.3 cadherin related 23 PSAP 10q22.1 prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy) CHST3 10q22.1 carbohydrate (chondroitin 6) sulfotransferase 3 SPOCK2 10pter-q25.3 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2 CGI-18 10pter-q25.3 CGI-18 protein LOC119504 10q22.2 hypothetical protein LOC119504 RTP801 DNAJB12 10q22.3 DnaJ (Hsp40) homolog, subfamily B, member 12 CBARA1 10q22.3 calcium binding atopy-related autoantigen 1 C10orf42 10q22.2 chromosome 10 open reading frame 42 FLJ39116 10q22.2-q22.3 oncoprotein induced transcript 3
    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)