{{.infobox .infobox-gene}}
| Symbol | WHRN |
| Full Name | Whirlin |
| Chromosome | 9q32 |
| NCBI Gene | 25861 |
| OMIM | 607928 |
| Ensembl | ENSG00000092140 |
| UniProt | Q9P202 |
| Protein Length | 906 amino acids |
| Molecular Weight | ~100 kDa |
WHRN (Whirlin), also known as DFNB31, encodes a scaffolding protein essential for the formation and maintenance of hair bundles in the inner ear's sensory hair cells[1]. Mutations in WHRN cause Usher syndrome type 2D, the most common form of syndromic hearing loss, as well as non-syndromic autosomal recessive hearing loss (DFNB31)[2]. The protein localizes to the stereocilia tips and bases, where it forms a critical complex with other Usher syndrome proteins including USH2A (usherin) and GPR98 (VLGR1)[3].
Whirlin is a PDZ domain-containing scaffolding protein that plays a central role in organizing the protein complex at stereocilia tips. The protein contains:
The protein functions as a molecular scaffold that:
During development, whirlin expression begins in embryonic stages and continues postnatally. The protein is essential for:
Usher syndrome is the most common cause of syndromic deafness-blindness. WHRN mutations account for a subset of Usher syndrome type 2, characterized by:
Biallelic WHRN mutations can also cause isolated hearing loss without visual impairment. This phenotype suggests that certain mutations may preferentially affect auditory function[8].
The whirler (wi) mouse carries a spontaneous mutation in the Whrn gene and serves as a valuable model for studying:
Studies in whirler mice have demonstrated that:
Zebrafish whrn orthologs have been used to study:
Whirlin interacts with several proteins critical for inner ear function:
| Partner Protein | Interaction Domain | Functional Significance |
|---|---|---|
| USH2A (Usherin) | PDZ1/PDZ2 | Ankle link formation |
| GPR98 (VLGR1) | PDZ1/PDZ2 | Large adhesion complex |
| ADGRV1 | PDZ domains | Mechanical stability |
| MYO7A | PDZ3 | Transport and localization |
| ESPN | PDZ domains | Stereocilia elongation |
AAV-mediated gene delivery of WHRN has shown promise in mouse models:
Current research explores:
Over 50 pathogenic variants have been identified in WHRN, including:
Whirlin mutations cause Usher syndrome type 2D. (2003). American Journal of Human Genetics. 2003. ↩︎
WHRN and nonsyndromic hearing loss. (2007). Human Genetics. 2007. ↩︎
Whirlin forms a giant complex with usherin and VLGR1. (2008). Journal of Biological Chemistry. 2008. ↩︎
The Usher protein interactome. (2015). Human Molecular Genetics. 2015. ↩︎
Whirlin is required for stereocilia maintenance. (2017). Journal of Neuroscience. 2017. ↩︎
Progressive hair bundle degeneration in whirler mice. (2010). Journal of the Association for Research in Otolaryngology. 2010. ↩︎
Clinical phenotype of Usher syndrome type 2D. (2012). Ophthalmic Genetics. 2012. ↩︎
DFNB31 hearing loss without visual impairment. (2009). European Journal of Human Genetics. 2009. ↩︎
AAV gene therapy for whirler mice. (2018). Molecular Therapy. 2018. ↩︎
Zebrafish whirlin in hair cell development. (2016). Development. 2016. ↩︎
Clinical trials for WHRN gene therapy. (2023). Gene Therapy. 2023. ↩︎
Hair cell regeneration approaches. (2021). Hearing Research. 2021. ↩︎
WHRN mutation spectrum database. (2020). Human Mutation. 2020. ↩︎
Epidemiology of WHRN-related disease. (2014). Orphanet Journal of Rare Diseases. 2014. ↩︎
Diagnostic approach to WHRN-related disease. (2018). Clinical Genetics. 2018. ↩︎