CDH23
cadherin related 23, the group of Cadherin related|MicroRNA protein coding host genes
Basic information
Region (hg38): 10:71396920-71815947
Previous symbols: [ "DFNB12", "USH1D" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- not_provided (4964 variants)
- Usher_syndrome_type_1 (973 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_12 (672 variants)
- Usher_syndrome_type_1D (582 variants)
- not_specified (570 variants)
- Inborn_genetic_diseases (471 variants)
- Pituitary_adenoma_5,_multiple_types (407 variants)
- CDH23-related_disorder (207 variants)
- Retinal_dystrophy (78 variants)
- Usher_syndrome (49 variants)
- Rare_genetic_deafness (41 variants)
- Hearing_loss,_autosomal_recessive (33 variants)
- Hearing_impairment (21 variants)
- Retinitis_pigmentosa-deafness_syndrome (18 variants)
- Atypical_Gaucher_Disease (14 variants)
- Metachromatic_leukodystrophy (14 variants)
- Combined_PSAP_deficiency (14 variants)
- Galactosylceramide_beta-galactosidase_deficiency (14 variants)
- Nonsyndromic_genetic_hearing_loss (10 variants)
- Childhood_onset_hearing_loss (8 variants)
- Optic_atrophy (5 variants)
- Retinitis_pigmentosa (4 variants)
- Ear_malformation (4 variants)
- Cone-rod_dystrophy (4 variants)
- Meniere_disease (2 variants)
- Intellectual_disability (2 variants)
- Usher_syndrome_type_2 (2 variants)
- Neurodevelopmental_abnormality (2 variants)
- Deafness (2 variants)
- See_cases (2 variants)
- Monogenic_hearing_loss (2 variants)
- USHER_SYNDROME,_TYPE_ID/F,_DIGENIC (2 variants)
- VATER_association (2 variants)
- Vitreoretinopathy (2 variants)
- Sensorineural_hearing_loss_disorder (2 variants)
- Usher_syndrome_type_2A (1 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_84A (1 variants)
- Beta-D-mannosidosis (1 variants)
- Bilateral_sensorineural_hearing_impairment (1 variants)
- Stickler_syndrome (1 variants)
- Syndromic_retinitis_pigmentosa (1 variants)
- Hereditary_cancer (1 variants)
- Non-Syndromic_Hereditary_Hearing_Impairment (1 variants)
- Prelingual_sensorineural_hearing_impairment (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. These statistics are base on transcript: NM_000022124.6. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 66 | 1709 | 19 | 1799 | ||
| missense | 19 | 99 | 1805 | 142 | 2073 | |
| nonsense | 74 | 47 | 122 | |||
| start loss | 1 | 1 | ||||
| frameshift | 177 | 127 | 10 | 314 | ||
| splice donor/acceptor (+/-2bp) | 40 | 142 | 188 | |||
| Total | 311 | 419 | 1887 | 1852 | 28 |
Highest pathogenic variant AF is 0.00017631473
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- essential_gene_gene_trap
- 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