USH1C
Harmonin, Usher Syndrome Type 1C
Gene Information Card
| Symbol | USH1C |
|---|---|
| Full Name | USH1C, harmonin, Usher syndrome type 1C |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 10083 ncbi.nlm.nih.gov/gene/10083 |
| Ensembl ID | ENSG00000106688 |
| UniProt ID | Q9Y6N9 |
| OMIM ID | 605242 |
| HGNC ID | 12597 |
| Aliases | DFNB18, DFNB18A, NY-CO-37, NY-CO-38, PDZ-73, PDZ-45, PDZ-73B, AIEBP, USH1C |
Description
The USH1C gene encodes harmonin, a scaffold protein containing PDZ domains that is essential for the development and maintenance of hair cell stereocilia in the inner ear and photoreceptor cells in the retina. Harmonin organizes protein complexes at the apical surface of sensory cells, linking cadherins and other transmembrane proteins to the actin cytoskeleton. Mutations in USH1C cause Usher syndrome type 1C (congenital deafness, vestibular dysfunction, and progressive retinitis pigmentosa) and autosomal recessive non-syndromic hearing loss DFNB18.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Usher syndrome type 1C (USH1C) | Loss-of-function mutations in USH1C disrupt harmonin-mediated scaffolding in cochlear hair cells and retinal photoreceptors, leading to sensory cell degeneration. | ClinVar, OMIM |
| Non-syndromic hearing loss DFNB18A | Biallelic USH1C mutations cause congenital profound sensorineural hearing loss without retinal involvement. | ClinVar, OMIM |
| Retinitis pigmentosa (syndromic) | Harmonin deficiency impairs photoreceptor outer segment morphogenesis and synaptic ribbon formation, leading to progressive vision loss. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cochlea | High | Tissue-specific (hair cells) |
| Retina | High | Tissue-specific (photoreceptors) |
| Testis | Moderate | GTEx |
| Kidney | Low | GTEx |
| Lung | Low | GTEx |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Hair cell (inner ear) | High | Essential for stereocilia bundle formation |
| Photoreceptor cell (retina) | High | Required for outer segment maintenance |
| HEK293 | Low | Overexpression studies |
| HeLa | Low | Endogenous expression minimal |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.216G>A (p.Trp72*) | Nonsense | Rare | Premature stop; loss of harmonin function; Usher syndrome type 1C |
| c.496C>T (p.Arg166*) | Nonsense | Rare | Truncated protein; severe hearing loss and retinitis pigmentosa |
| c.238_239insC (p.Leu80Profs*28) | Frameshift | Rare | Loss of PDZ domain; Usher syndrome type 1C |
| c.919-2A>G | Splice acceptor | Rare | Exon skipping; non-syndromic hearing loss DFNB18A |
Mutation functional classification
Loss of Function (LOF)
Most USH1C mutations are loss-of-function (nonsense, frameshift, splice-site) leading to truncated or absent harmonin protein, causing Usher syndrome type 1C or DFNB18A.
Gain of Function (GOF)
No gain-of-function mutations reported for USH1C.
Dominant Negative (DN)
No dominant-negative mutations reported; USH1C disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Usher syndrome (KEGG: hsa05145)
• Phototransduction cascade
• Stereocilium organization
Protein Summary
Harmonin is a multi-PDZ domain scaffold protein (isoforms a, b, c) that localizes to the apical region of inner ear hair cells and retinal photoreceptors. It interacts with cadherin 23 (CDH23), protocadherin 15 (PCDH15), and myosin VIIa (MYO7A) to form the ankle-link complex of stereocilia and the periciliary complex in photoreceptors. Harmonin anchors these complexes to the actin cytoskeleton, essential for mechanotransduction and cell survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USH1C Knockout HEK293 Cell Line | EDJ-KQ6890 | Human | 10083 | Details Get a Quote |
| USH1C Knockout HCT 116 Cell Line | EDJ-KQ30125 | Human | 10083 | Details Get a Quote |
| USH1C Knockout A-549 Cell Line | EDJ-KQ31497 | Human | 10083 | Details Get a Quote |
| USH1C Knockout HeLa Cell Line | EDJ-KQ31499 | Human | 10083 | Details Get a Quote |
