PCDH15

protocadherin related 15, the group of Cadherin related|MicroRNA protein coding host genes

Basic information

Region (hg38): 10:53802771-55627942

Previous symbols: [ "USH1F", "DFNB23" ]

Links

ENSG00000150275

∙ NCBI:65217 ∙ OMIM:605514 ∙ HGNC:14674 ∙ Uniprot:Q96QU1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Usher syndrome type 1F (Strong), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 23 (Limited), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 23 (Definitive), mode of inheritance: AR
hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
Usher syndrome type 1 (Supportive), mode of inheritance: AR
Usher syndrome type 1F (Definitive), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 23 (Strong), mode of inheritance: AR
Usher syndrome type 1F (Strong), mode of inheritance: AR
Usher syndrome type 1 (Definitive), mode of inheritance: AR
nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 23; Usher syndrome, type 1F; Usher syndrome, type 1D	AR/Digenic	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	11398101; 14570705; 15537665; 17653769; 18719945; 19107147
Inheritance of some conditions can be digenic, involving CDH23

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCDH15 gene.

not_provided (2831 variants)
Usher_syndrome_type_1F (875 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_23 (315 variants)
Inborn_genetic_diseases (290 variants)
not_specified (265 variants)
Usher_syndrome_type_1D (197 variants)
Usher_syndrome_type_1 (139 variants)
PCDH15-related_disorder (85 variants)
Retinal_dystrophy (18 variants)
Hearing_loss,_autosomal_recessive (11 variants)
Rare_genetic_deafness (10 variants)
Usher_syndrome (9 variants)
Retinitis_pigmentosa-deafness_syndrome (8 variants)
Hearing_impairment (5 variants)
Optic_atrophy (3 variants)
USHER_SYNDROME,_TYPE_ID/F,_DIGENIC (2 variants)
Usher_syndrome_type_1G (2 variants)
Meniere_disease (1 variants)
Retinitis_pigmentosa (1 variants)
Progressive_cone_dystrophy_(without_rod_involvement) (1 variants)
Aganglionic_megacolon (1 variants)
Ear_malformation (1 variants)
Nonsyndromic_Deafness (1 variants)
See_cases (1 variants)
Non-Syndromic_Hereditary_Hearing_Impairment (1 variants)
Childhood_onset_hearing_loss (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCDH15 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001384140.1. 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			22 clinvar	698 clinvar	1 clinvar	721
missense	2 clinvar	12 clinvar	745 clinvar	48 clinvar	9 clinvar	816
nonsense	54 clinvar	38 clinvar	13 clinvar			105
start loss		1	1			2
frameshift	98 clinvar	96 clinvar	42 clinvar			236
splice donor/acceptor (+/-2bp)	8 clinvar	90 clinvar	14 clinvar	1 clinvar		113
Total	162	237	837	747	10

Highest pathogenic variant AF is 0.0001233174

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCDH15	protein_coding	protein_coding	ENST00000361849	33	1825172

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.03e-25	0.994	125198	1	549	125748	0.00219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.68	1196	1.04e+3	1.15	0.0000543	12747
Missense in Polyphen		433	379.09	1.1422		4666
Synonymous	-1.87	422	376	1.12	0.0000206	3970
Loss of Function	3.11	52	82.5	0.630	0.00000468	1011

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0137	0.0138
Ashkenazi Jewish	0.00437	0.00437
East Asian	0.00261	0.00256
Finnish	0.000416	0.000416
European (Non-Finnish)	0.00130	0.00129
Middle Eastern	0.00261	0.00256
South Asian	0.00131	0.00131
Other	0.00163	0.00163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Calcium-dependent cell-adhesion protein. Essential for maintenance of normal retinal and cochlear function.;
Disease: DISEASE: Usher syndrome 1F (USH1F) [MIM:602083]: 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:15660226, ECO:0000269|PubMed:22815625}. 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, ECO:0000269|PubMed:18719945}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 23 (DFNB23) [MIM:609533]: 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:14570705, ECO:0000269|PubMed:18719945, ECO:0000269|PubMed:28281779}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.178

Intolerance Scores

loftool: 0.995
rvis_EVS: 0.74
rvis_percentile_EVS: 86.35

Haploinsufficiency Scores

pHI: 0.252
hipred: Y
hipred_score: 0.543
ghis: 0.494

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0375

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pcdh15
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; hearing/vestibular/ear 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); growth/size/body region phenotype; muscle phenotype; cellular phenotype;

Zebrafish Information Network

Gene name: pcdh15a
Affected structure: neuromast hair cell
Phenotype tag: abnormal
Phenotype quality: decreased functionality

Gene ontology

Biological process: cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;sensory perception of sound;photoreceptor cell maintenance;inner ear development;sensory perception of light stimulus;equilibrioception
Cellular component: photoreceptor outer segment;extracellular region;integral component of plasma membrane;stereocilium;synapse
Molecular function: calcium ion binding