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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
USH1C
USH1 protein network component harmonin
Chromosome 11 Β· 11p15.1
NCBI Gene: 10083Ensembl: ENSG00000006611.18HGNC: HGNC:12597UniProt: A0A0S2Z4U9
82PubMed Papers
22Diseases
0Drugs
199Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingspectrin bindingG2/M transition of mitotic cell cyclesensory perception of soundUsher syndrome type 1Cautosomal recessive nonsyndromic hearing loss 18AUsher syndrome type 1Usher syndrome
✦AI Summary

USH1C encodes harmonin, a scaffolding protein essential for mechanotransduction in sensory organs. As a core component of the USH interactome, harmonin organizes a protein network with USH1G, CDH23, and MYO7A that mediates stereocilia development and maintenance in cochlear hair cells 1. In the retina, harmonin localizes to the periciliary region of photoreceptors and outer limiting membrane, where it maintains structural integrity and facilitates molecular trafficking between photoreceptor segments 2. Harmonin also functions as a central regulatory component of the intermicrovillar adhesion complex (IMAC), recruiting cadherins (CDHR2, CDHR5) and myosin 7B to stabilize microvilli in intestinal tuft cells and other epithelial tissues 3. Pathogenic USH1C mutations cause Usher syndrome type 1C, an autosomal recessive syndromic ciliopathy characterized by congenital sensorineural hearing loss and progressive retinitis pigmentosa 4. In genetic screening studies, USH1C mutations account for approximately 10-14.9% of USH1 cases 56. The diverse subcellular localization of harmonin isoforms in photoreceptors, MΓΌller glia, and cone synapses correlates with the clinical phenotype in USH1C patients 2. Gene therapy delivery of harmonin_a1 transcript shows promise in reversing primary cilia defects in patient-derived cells, suggesting therapeutic potential for restoring inner ear and retinal function.

Sources cited
1
USH1C harmonin is essential for stereocilia development and maintenance in the organ of Corti; USH protein network is located in periciliary region of photoreceptors
PMID: 34201633
2
Harmonin localizes to MΓΌller glia terminal endfeet, cone pedicles, rod outer segments, and outer limiting membrane; harmonin_a1 is most abundant USH1C transcript; gene therapy delivery of harmonin_a1 reverts primary cilia defects in USH1C patient fibroblasts
PMID: 35997788
3
USH1C is a component of intermicrovillar adhesion complexes (IMAC) in intestinal tuft cells; USH1C colocalizes with CDHR2 and CDHR5
PMID: 39360911
4
USH1C mutations cause Usher syndrome type 1C, an autosomal recessive syndromic ciliopathy with congenital sensorineural hearing loss and progressive retinitis pigmentosa
PMID: 35353227
5
USH1C mutations account for 10% of USH1 families in Chinese patient cohort
PMID: 29625443
6
USH1C accounts for 14.9% of USH1 families in UK patient cohort; c.496+1G>A is most common USH1C mutation
PMID: 22135276
Disease Associationsβ“˜22
Usher syndrome type 1COpen Targets
0.75Strong
autosomal recessive nonsyndromic hearing loss 18AOpen Targets
0.73Strong
Usher syndrome type 1Open Targets
0.66Moderate
Usher syndromeOpen Targets
0.62Moderate
deafnessOpen Targets
0.59Moderate
Retinal dystrophyOpen Targets
0.51Moderate
hearing loss, autosomal recessiveOpen Targets
0.50Moderate
Usher syndrome type 2Open Targets
0.46Moderate
retinitis pigmentosaOpen Targets
0.43Moderate
Rare genetic deafnessOpen Targets
0.43Moderate
genetic disorderOpen Targets
0.42Moderate
hearing lossOpen Targets
0.37Weak
eye diseaseOpen Targets
0.37Weak
Hearing impairmentOpen Targets
0.33Weak
Methicillin-Resistant Staphylococcus Aureus InfectionOpen Targets
0.31Weak
optic atrophyOpen Targets
0.16Weak
Meniere diseaseOpen Targets
0.12Weak
autosomal dominant nonsyndromic hearing lossOpen Targets
0.08Suggestive
Barrett's esophagusOpen Targets
0.08Suggestive
autosomal recessive nonsyndromic hearing loss 9Open Targets
0.07Suggestive
Deafness, autosomal recessive, 18AUniProt
Usher syndrome 1CUniProt
Pathogenic Variants199
NM_153676.4(USH1C):c.1039C>T (p.Gln347Ter)Pathogenic
not provided|Usher syndrome type 1C|Autosomal recessive nonsyndromic hearing loss 18A|USH1C-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 347
NM_153676.4(USH1C):c.2401G>T (p.Glu801Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2026β†’ Residue 801
NM_153676.4(USH1C):c.2326dup (p.Ile776fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C|not provided|USH1C-related disorder|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2026β†’ Residue 776
NM_153676.4(USH1C):c.216G>A (p.Val72=)Pathogenic
Usher syndrome type 1C|Usher syndrome type 1|not provided|Usher syndrome|Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C;Usher syndrome type 1|Autosomal recessive nonsyndromic hearing loss 18A|Rare genetic deafness|USH1C-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 72
NM_153676.4(USH1C):c.497-2delPathogenic
Usher syndrome type 1C|Usher syndrome type 1|Autosomal recessive nonsyndromic hearing loss 18A|Retinal dystrophy|Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C|not provided
β˜…β˜…β˜†β˜†2026
NM_153676.4(USH1C):c.586C>T (p.Arg196Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18A
β˜…β˜…β˜†β˜†2026β†’ Residue 196
NM_153676.4(USH1C):c.91C>T (p.Arg31Ter)Pathogenic
Usher syndrome type 1C|not provided|Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C;Usher syndrome type 1|Autosomal recessive nonsyndromic hearing loss 18A
β˜…β˜…β˜†β˜†2025β†’ Residue 31
NM_153676.4(USH1C):c.2490+1G>ALikely pathogenic
not provided|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025
NM_153676.4(USH1C):c.579+1G>APathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025
NM_153676.4(USH1C):c.1096del (p.Glu366fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18A|not provided|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 366
NM_153676.4(USH1C):c.238dup (p.Arg80fs)Pathogenic
Usher syndrome type 1C|Usher syndrome type 1|Usher syndrome|Retinal dystrophy|not provided|Rare genetic deafness|Autosomal recessive nonsyndromic hearing loss 18A|Retinitis pigmentosa|USH1C-related disorder|Hearing loss, autosomal recessive|Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 80
NM_153676.4(USH1C):c.491_492del (p.Val164fs)Pathogenic
Retinal dystrophy|not provided|Usher syndrome type 1C;Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 164
NM_153676.4(USH1C):c.308G>A (p.Arg103His)Pathogenic
Usher syndrome type 1C|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1|Usher syndrome type 1C;Autosomal recessive nonsyndromic hearing loss 18A|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 103
NM_153676.4(USH1C):c.877-1G>APathogenic
Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C|Autosomal recessive nonsyndromic hearing loss 18A|not provided|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025
NM_153676.4(USH1C):c.496+1G>APathogenic
Usher syndrome type 1C|not provided|Inborn genetic diseases|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C;Autosomal recessive nonsyndromic hearing loss 18A
β˜…β˜…β˜†β˜†2025
NM_153676.4(USH1C):c.1139del (p.Gly379_Ser380insTer)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C|not provided|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 379
NM_153676.4(USH1C):c.24del (p.Glu8fs)Pathogenic
not provided|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 8
NM_153676.4(USH1C):c.658C>T (p.Arg220Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C;Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C;Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 220
NM_153676.4(USH1C):c.375del (p.Ser125fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025β†’ Residue 125
NM_153676.4(USH1C):c.579+1G>CPathogenic
Autosomal recessive nonsyndromic hearing loss 18A;Usher syndrome type 1C|not provided|Autosomal recessive nonsyndromic hearing loss 18A|Usher syndrome type 1C
β˜…β˜…β˜†β˜†2025
View on ClinVar β†—
Related Genes
MYO7BProtein interaction99%USHBP1Protein interaction93%PDZD7Protein interaction92%CDHR5Protein interaction91%CDHR2Protein interaction90%OTOGProtein interaction86%
Tissue Expression6 tissues
Brain
100%
Liver
17%
Heart
2%
Bone Marrow
1%
Ovary
1%
Lung
1%
Gene Interaction Network
Click a node to explore
USH1CMYO7BUSHBP1PDZD7CDHR5CDHR2OTOG
PROTEIN STRUCTURE
Preparing viewer…
PDB5XBF Β· 1.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.88LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.62–0.88]
RankingsWhere USH1C stands among ~20K protein-coding genes
  • #5,835of 20,598
    Most Researched82
  • #339of 5,498
    Most Pathogenic Variants199 Β· top 10%
  • #7,759of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedUSH1C
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.
PMID: 29625443
Invest Ophthalmol Vis Sci Β· 2018
1.00
2
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.
PMID: 22135276
J Med Genet Β· 2012
0.90
3
Usher Syndrome: Genetics of a Human Ciliopathy.
PMID: 34201633
Int J Mol Sci Β· 2021
0.80
4
HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.
PMID: 38909044
Nat Commun Β· 2024
0.70
5
The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification.
PMID: 35353227
Hum Genet Β· 2022
0.60