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FLASH GENE

Symbol

CDH23

contributors: mct/pgu - updated : 07-06-2017

HGNC name	cadherin related 23
HGNC id	13733

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner cochlea Corti   Homo sapiens Visual eye retina

cells

System Cell Pubmed Species Stage Rna symbol Hearing / Equilibrium cochlea cell Homo sapiens Hearing / Equilibrium stereocilia Visual cone 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)