PCDH15
Protocadherin-15, a key component of the hair-cell mechanotransduction complex involved in hearing and balance.
Gene Information Card
| Symbol | PCDH15 |
|---|---|
| Full Name | Protocadherin-15 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.1 |
| NCBI Gene ID | 65217 ncbi.nlm.nih.gov/gene/65217 |
| Ensembl ID | ENSG00000150275 |
| UniProt ID | Q96QU1 |
| OMIM ID | 605514 |
| HGNC ID | 14674 |
| Aliases | USH1F, DFNB23, CDHR15, PCDH15L |
Description
PCDH15 encodes protocadherin-15, a member of the cadherin superfamily of calcium-dependent cell adhesion proteins. It is essential for the formation and function of the hair-cell mechanotransduction complex in the inner ear and retina. Mutations in PCDH15 cause Usher syndrome type 1F (USH1F) and nonsyndromic autosomal recessive deafness (DFNB23).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Usher syndrome type 1F (USH1F) | Loss-of-function mutations disrupt hair-cell stereocilia bundle integrity and retinal photoreceptor cell function, leading to congenital deafness, vestibular dysfunction, and progressive retinitis pigmentosa. | OMIM #602083; ClinVar |
| Nonsyndromic hearing loss (DFNB23) | Biallelic missense or truncating mutations impair mechanotransduction in cochlear hair cells without retinal involvement. | OMIM #609533; ClinVar |
| Retinitis pigmentosa (isolated) | Rare PCDH15 variants may contribute to photoreceptor degeneration in the absence of hearing loss. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cochlea | Not available (GTEx nTPM) | High (RNA-seq from inner ear) |
| Retina | Not available (GTEx nTPM) | High (RNA-seq from retina) |
| Testis | 0.0 | Not detected |
| Brain (cerebellum) | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.0 | No endogenous expression |
| ARPE-19 (retinal pigment epithelium) | 0.0 | No endogenous expression |
| Hair cell (mouse) | Not applicable | High expression in stereocilia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2455C>T (p.Arg819*) | Nonsense | Rare (founder in Ashkenazi Jewish) | Loss of function; truncation of the extracellular domain |
| c.3340G>A (p.Gly1114Arg) | Missense | Rare | Disrupts calcium binding in cadherin repeat |
| c.475G>A (p.Gly159Arg) | Missense | Rare | Impairs protein trafficking to stereocilia |
| c.3823C>T (p.Arg1275*) | Nonsense | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that lead to truncated or absent protocadherin-15 protein, causing Usher syndrome type 1F or DFNB23.
Gain of Function (GOF)
Not reported for PCDH15.
Dominant Negative (DN)
Not reported; all known pathogenic mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Usher syndrome pathway (KEGG: hsa05168)
• Stereocilium assembly and mechanotransduction (Reactome: R-HSA-9662360)
Protein Summary
Protocadherin-15 is a single-pass transmembrane protein with 11 extracellular cadherin repeats, a transmembrane domain, and a cytoplasmic tail. It forms tip-link filaments with cadherin-23 (CDH23) in hair-cell stereocilia, essential for mechanoelectrical transduction. In the retina, it localizes to the calyceal processes of photoreceptors, supporting cell adhesion and survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCDH15 Knockout HEK293 Cell Line | EDJ-KQ14700 | Human | 65217 | Details Get a Quote |
| PCDH15 Knockout HeLa Cell Line | EDJ-KQ57103 | Human | 65217 | Details Get a Quote |
| PCDH15 Knockout A-549 Cell Line | EDJ-KQ65618 | Human | 65217 | Details Get a Quote |
| PCDH15 Knockout HCT 116 Cell Line | EDJ-KQ74043 | Human | 65217 | Details Get a Quote |
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