CDH23

cadherin related 23, the group of Cadherin related|MicroRNA protein coding host genes

Basic information

Region (hg38): 10:71396919-71815947

Previous symbols: [ "DFNB12", "USH1D" ]

Links

ENSG00000107736 ∙ NCBI:64072 ∙ OMIM:605516 ∙ HGNC:13733 ∙ Uniprot:Q9H251 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Usher syndrome type 1D (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 12 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 12 (Definitive), mode of inheritance: AR
• Usher syndrome type 1D (Definitive), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Usher syndrome type 1 (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 12 (Strong), mode of inheritance: AR
• Usher syndrome type 1D (Strong), mode of inheritance: AR
• Usher syndrome type 1 (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pituitary adenoma 5, multiple types; Deafness, autosomal recessive 12; Usher syndrome, type 1D; Usher syndrome, type 1D /F digenic	AD/AR/Digenic	Audiologic/Otolaryngologic; Oncologic	For Pituitary adenoma, multiple types, awareness may allow early diagnosis and management of pituitary neoplasms; For Deafness and Usher syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Oncologic; Ophthalmologic	11138009; 11090341; 11138008; 15537665; 17850630; 28413019
Inheritance of Usher syndrome can be digenic, involving PCDH15

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDH23 gene.

• not provided (4274 variants)
• Usher syndrome type 1 (724 variants)
• not specified (585 variants)
• Autosomal recessive nonsyndromic hearing loss 12 (514 variants)
• Usher syndrome type 1D (478 variants)
• Pituitary adenoma 5, multiple types (198 variants)
• Inborn genetic diseases (170 variants)
• CDH23-Related Disorders (99 variants)
• Retinitis pigmentosa-deafness syndrome (45 variants)
• Usher syndrome (37 variants)
• Rare genetic deafness (37 variants)
• Nonsyndromic Hearing Loss, Recessive (34 variants)
• Combined PSAP deficiency (31 variants)
• Usher syndrome type 1D;Autosomal recessive nonsyndromic hearing loss 12;Pituitary adenoma 5, multiple types (29 variants)
• Metachromatic leukodystrophy (29 variants)
• Galactosylceramide beta-galactosidase deficiency (29 variants)
• Atypical Gaucher Disease (29 variants)
• Autosomal recessive nonsyndromic hearing loss 12;Usher syndrome type 1D;Pituitary adenoma 5, multiple types (27 variants)
• Retinal dystrophy (25 variants)
• Usher syndrome type 1D;Pituitary adenoma 5, multiple types;Autosomal recessive nonsyndromic hearing loss 12 (22 variants)
• Autosomal recessive nonsyndromic hearing loss 12;Pituitary adenoma 5, multiple types;Usher syndrome type 1D (21 variants)
• Pituitary adenoma 5, multiple types;Usher syndrome type 1D;Autosomal recessive nonsyndromic hearing loss 12 (18 variants)
• Hearing impairment (16 variants)
• Hearing loss, autosomal recessive (13 variants)
• CDH23-related condition (12 variants)
• Pituitary adenoma 5, multiple types;Autosomal recessive nonsyndromic hearing loss 12;Usher syndrome type 1D (12 variants)
• Nonsyndromic genetic hearing loss (10 variants)
• Childhood onset hearing loss (8 variants)
• Ear malformation (4 variants)
• Retinitis pigmentosa (3 variants)
• Usher syndrome type 1D;Autosomal recessive nonsyndromic hearing loss 12 (3 variants)
• See cases (2 variants)
• Sensorineural hearing loss disorder (2 variants)
• USHER SYNDROME, TYPE ID/F, DIGENIC (2 variants)
• Meniere disease (2 variants)
• Usher syndrome type 1;Usher syndrome type 1D (2 variants)
• Sphingolipid activator protein 1 deficiency (2 variants)
• Neurodevelopmental abnormality (2 variants)
• Usher syndrome type 2 (2 variants)
• Krabbe disease due to saposin A deficiency (2 variants)
• Gaucher disease due to saposin C deficiency (2 variants)
• CDH23-related disorder (1 variants)
• Hearing impairment;Bilateral sensorineural hearing impairment (1 variants)
• Usher syndrome type 1D;Autosomal recessive nonsyndromic hearing loss 84A (1 variants)
• Deafness (1 variants)
• Non-Syndromic Hereditary Hearing Impairment (1 variants)
• - (1 variants)
• Usher syndrome type 2A;Autosomal recessive nonsyndromic hearing loss 12 (1 variants)
• Hereditary cancer (1 variants)
• Beta-D-mannosidosis (1 variants)
• Stickler syndrome (1 variants)
• Prelingual sensorineural hearing impairment;Usher syndrome type 1D (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDH23 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			15	1300	17	1332
missense	17	38	1406	48	14	1523
nonsense	55	25	1			81
start loss			1			1
frameshift	133	72	6			211
inframe indel		3	15			18
splice donor/acceptor (+/-2bp)	23	106	3	1	1	134
splice region	2	2	71	193	6	274
non coding	2		48	527	199	776
Total	230	244	1495	1876	231

Highest pathogenic variant AF is 0.000145

Variants in CDH23

This is a list of pathogenic ClinVar variants found in the CDH23 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-71396971-C-G		Usher syndrome type 1D • Autosomal recessive nonsyndromic hearing loss 12	Uncertain significance (Jan 12, 2018)
10-71396978-G-T		Usher syndrome type 1D • Autosomal recessive nonsyndromic hearing loss 12 • CDH23-related disorder	Uncertain significance (Jan 12, 2018)
10-71397048-G-A		Usher syndrome type 1D • Autosomal recessive nonsyndromic hearing loss 12 • CDH23-related disorder	Uncertain significance (Jan 13, 2018)
10-71397066-G-A		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D	Benign/Likely benign (May 12, 2021)
10-71397124-TGCGAGCG-T		Nonsyndromic Hearing Loss, Recessive • Retinitis pigmentosa-deafness syndrome • CDH23-related disorder	Uncertain significance (Jun 14, 2016)
10-71397124-T-TGCGAGCG		Nonsyndromic Hearing Loss, Recessive • Retinitis pigmentosa-deafness syndrome • CDH23-related disorder	Conflicting classifications of pathogenicity (Oct 18, 2021)
10-71397139-G-C		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D	Uncertain significance (Jan 12, 2018)
10-71397156-C-T		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D • CDH23-related disorder	Uncertain significance (Jan 12, 2018)
10-71397187-G-A			Uncertain significance (Jun 29, 2021)
10-71397269-G-A		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D	Uncertain significance (Apr 28, 2017)
10-71397276-CCGAGG-C		Retinitis pigmentosa-deafness syndrome • Nonsyndromic Hearing Loss, Recessive • not specified	Benign/Likely benign (Jun 14, 2016)
10-71397276-C-CCGAGG		Retinitis pigmentosa-deafness syndrome • Nonsyndromic Hearing Loss, Recessive • not specified • CDH23-related disorder	Benign/Likely benign (Jul 15, 2020)
10-71397286-G-C		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D • CDH23-related disorder	Uncertain significance (Jan 13, 2018)
10-71397289-A-AAGGCG			Benign (Mar 03, 2015)
10-71397309-C-A		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D • not specified • CDH23-related disorder	Conflicting classifications of pathogenicity (Jan 13, 2018)
10-71397331-A-C		Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D	Uncertain significance (Mar 16, 2018)
10-71439576-A-G			Benign (Jun 14, 2018)
10-71439701-T-G			Benign (Oct 27, 2018)
10-71439744-C-A		Usher syndrome type 1D • Autosomal recessive nonsyndromic hearing loss 12	Benign (Jul 01, 2021)
10-71439831-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1D • Usher syndrome type 1	Benign (Jul 01, 2021)
10-71439832-A-T			Uncertain significance (Sep 04, 2021)
10-71439836-GGC-G		Usher syndrome	Pathogenic (Dec 31, 2022)
10-71439838-C-T		not specified • Usher syndrome type 1D • Autosomal recessive nonsyndromic hearing loss 12 • Usher syndrome type 1	Benign (Feb 01, 2024)
10-71439838-CG-C			Pathogenic (Mar 27, 2022)
10-71439839-G-A		not specified • Usher syndrome type 1	Uncertain significance (Oct 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDH23	protein_coding	protein_coding	ENST00000398788	22	419012

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000318	1.00	124661	0	36	124697	0.000144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.707	662	715	0.926	0.0000471	7218
Missense in Polyphen		116	141.92	0.81739		1424
Synonymous	0.510	290	301	0.963	0.0000209	2270
Loss of Function	3.93	18	47.1	0.382	0.00000231	521

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000433	0.000431
Ashkenazi Jewish	0.000105	0.0000993
East Asian	0.0000556	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.0000556	0.0000556
South Asian	0.000164	0.000163
Other	0.000183	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining the proper organization of the stereocilia bundle of hair cells in the cochlea and the vestibule during late embryonic/early postnatal development. It is part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing. {ECO:0000269|PubMed:11138009, ECO:0000269|PubMed:16679490}.
• Disease: DISEASE: Usher syndrome 1D (USH1D) [MIM:601067]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. {ECO:0000269|PubMed:11138009, ECO:0000269|PubMed:12075507, ECO:0000269|PubMed:15660226, ECO:0000269|PubMed:16679490, ECO:0000269|PubMed:18429043}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Usher syndrome 1D/F (USH1DF) [MIM:601067]: USH1DF patients are heterozygous for mutations in CDH23 and PCDH15, indicating a digenic inheritance pattern. {ECO:0000269|PubMed:15537665}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 12 (DFNB12) [MIM:601386]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:11090341, ECO:0000269|PubMed:12075507, ECO:0000269|PubMed:12522556, ECO:0000269|PubMed:15829536, ECO:0000269|PubMed:16679490, ECO:0000269|PubMed:17850630, ECO:0000269|PubMed:22899989, ECO:0000269|PubMed:24767429}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pituitary adenoma 5, multiple types (PITA5) [MIM:617540]: A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete: growth hormone (GH)-secreting, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid- stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors. Familial and sporadic forms have been reported. The transmission pattern of familial PITA5 is consistent with autosomal dominant inheritance with reduced penetrance. {ECO:0000269|PubMed:28413019}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.591
• rvis_EVS: -1.84
• rvis_percentile_EVS: 2.06

Haploinsufficiency Scores

• pHI: 0.321
• hipred: Y
• hipred_score: 0.542
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.817

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Cdh23
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; reproductive system phenotype

Zebrafish Information Network

• Gene name: cdh23
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: physical object quality

Gene ontology

• Biological process: calcium ion transport;homophilic cell adhesion via plasma membrane adhesion molecules;visual perception;sensory perception of sound;locomotory behavior;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;photoreceptor cell maintenance;response to stimulus;sensory perception of light stimulus;equilibrioception;regulation of cytosolic calcium ion concentration;inner ear receptor cell stereocilium organization
• Cellular component: plasma membrane;membrane;integral component of membrane;stereocilium
• Molecular function: calcium ion binding;protein binding