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CDH23
cadherin related 23
The CDH23 gene provides instructions for producing cadherin 23, a protein crucial for cell adhesion and the proper function of the inner ear and retina. CDH23 is essential for the formation and function of hair bundles in the inner ear, which are vital for hearing and balance.
CDH23 is located on the long (q) arm of chromosome 10, at band 10q22.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The CDH23 gene encodes cadherin 23, a protein involved in cell-to-cell adhesion. This protein is particularly important in the sensory cells of the inner ear and the photoreceptor cells of the retina. Different forms of the cadherin 23 protein are produced in various tissues, including a shorter version in the retina and a longer one in the inner ear.
Disruptions to the CDH23 gene can lead to conditions primarily affecting hearing and vision, such as Usher syndrome.
What the gene does
Cadherin 23 functions as a cell adhesion protein, helping cells bind together. In the inner ear, it forms part of a complex that helps shape and maintain hair bundles, which are structures made of stereocilia. These stereocilia bend in response to sound waves and head movements, converting these mechanical stimuli into nerve impulses essential for hearing and balance.
The protein interacts with other components of the cell membrane to facilitate cell attachment, and its role in the inner ear is critical for the proper functioning of both the auditory and vestibular systems. While its exact role in the retina is not fully defined, research indicates it is important for photoreceptor cell function, which enables light and colour detection.
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Chromosome location
The CDH23 gene is located on chromosome 10, specifically at position 10q22.1. This position refers to the long (q) arm of chromosome 10, in region 2, band 2, sub-band 1.
Protein structure
The cadherin 23 protein is a large protein, consisting of 3354 amino acids. It features multiple cadherin domains, which are characteristic of cell adhesion proteins. These include Cadherin 1 (amino acids 34-132), Cadherin 2 (amino acids 133-236), Cadherin 3 (amino acids 237-348), Cadherin 4 (amino acids 349-460), Cadherin 5 (amino acids 461-561), Cadherin 6 (amino acids 562-671), Cadherin 7 (amino acids 672-784), Cadherin 8 (amino acids 779-890), Cadherin 9 (amino acids 891-995), Cadherin 10 (amino acids 996-1102), Cadherin 11 (amino acids 1103-1208), Cadherin 12 (amino acids 1210-1313), Cadherin 13 (amino acids 1314-1418), Cadherin 14 (amino acids 1420-1527), and Cadherin 15 (amino acids 1529-1634).
Key variants
Variants in the CDH23 gene can alter the structure or production of the cadherin 23 protein, impacting its ability to facilitate cell adhesion and proper sensory function. Many pathogenic variants lead to a non-functional or abnormally shortened protein. These changes are associated with various forms of hearing and vision impairment.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1112_1115del | p.Ile371fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary adenoma 5, multiple types |
c.1179del | p.Asn393fs | Pathogenic/Likely pathogenic | ★★☆☆ | Usher syndrome type 1 |
c.4488+2T>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary adenoma 5, multiple types |
c.494dup | p.Ser166fs | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 12 |
c.5256dup | p.Glu1753Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary adenoma 5, multiple types |
c.6517G>T | p.Glu2173Ter | Pathogenic | ★★☆☆ | Pituitary adenoma 5, multiple types |
c.7086C>G | p.Tyr2362Ter | Pathogenic | ★★☆☆ | Usher syndrome |
c.7730_7734del | p.Phe2577fs | Pathogenic | ★★☆☆ | Usher syndrome type 1D |
c.7872+1G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary adenoma 5, multiple types |
c.8847C>G | p.Tyr2949Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Usher syndrome type 1 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the CDH23 gene are primarily associated with inherited hearing and vision loss. The most notable condition linked to CDH23 is Usher syndrome type 1, specifically Usher syndrome type 1D (USH1D), which is characterised by combined hearing loss, vision loss, and balance issues. CDH23 variants can also contribute to nonsyndromic hearing loss and age-related hearing loss.
- Usher syndrome type 1 Dedicated page coming soon
UK clinical status
The CDH23 gene is included in several expert-curated panels within the UK NHS Genomic Medicine Service's PanelApp. It is rated 'Green' for the DDG2P panel, the Monogenic hearing loss panel (R67), and the Retinal disorders panel (R32), indicating strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the CDH23 gene?
The CDH23 gene provides instructions for making cadherin 23, a protein that helps cells adhere to one another. It is crucial for the development and function of hair bundles in the inner ear, which are vital for hearing and balance, and also plays a role in the retina.
Which conditions are associated with variants in the CDH23 gene?
Variants in the CDH23 gene are primarily associated with Usher syndrome type 1 (specifically USH1D), which involves hearing loss, vision loss, and balance problems. It can also be linked to nonsyndromic hearing loss and contribute to age-related hearing loss.
How is CDH23 related to hearing and balance?
In the inner ear, the cadherin 23 protein is part of a complex that helps form hair bundles. These structures contain stereocilia that bend in response to sound waves and head movements, converting them into nerve signals for both hearing and maintaining balance.
References
- Miyagawa M, Nishio SY, Usami S. Prevalence and clinical features of hearing loss patients with CDH23 mutations: a large cohort study. PloS one. 2012. PMID: 22899989
- Schultz JM, Bhatti R, Madeo AC. Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes. Journal of medical genetics. 2011. PMID: 21940737
- Oshima A, Jaijo T, Aller E. Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I. Human mutation. 2008. PMID: 18429043
- Siemens J, Lillo C, Dumont RA. Cadherin 23 is a component of the tip link in hair-cell stereocilia. Nature. 2004. PMID: 15057245
- Astuto LM, Bork JM, Weston MD. CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness. American journal of human genetics. 2002. PMID: 12075507
- Bork JM, Peters LM, Riazuddin S. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. American journal of human genetics. 2001. PMID: 11090341
- Bolz H, von Brederlow B, Ramírez A. Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nature genetics. 2001. PMID: 11138009