ArticleHuman mutation2020
Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Identification of a novel isoform of Slc26a4 by single-cell RNA-sequencing of pendrin-expressing cells in the cochlea.Human genetics · 2026Article
- Mutational spectrum of SLC26A4 and SLC26A5 associated with hereditary hearing loss in Moroccan families.Human genomics · 2026Article
- A UniqueInternational journal of molecular sciences · 2026Article
- OtoVCE: a mechanism-aware language-model evidence layer for hereditary hearing-loss variant interpretation.Frontiers in genetics · 2026Article
- Assessing the Functional Significance of Novel and Rare Variants of theInternational journal of molecular sciences · 2025Article
- Hearing Loss and Audiogenic Seizures Induced by Hypofunctional Prestin Variants.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Genetic heterogeneity in patients with enlarged vestibular aqueduct and Pendred syndrome.Molecular medicine (Cambridge, Mass.) · 2025Article
- Inhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants.International journal of molecular medicine · 2025Article
- Novel genetic determinants contribute to hearing loss in a central European cohort with enlarged vestibular aqueduct.Molecular medicine (Cambridge, Mass.) · 2025Article
- SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.Science advances · 2024Article
- Spectrum of genetic variants in 306 patients with non-syndromic hearing loss from Croatia.Croatian medical journal · 2024Article
- The pathogenic roles of the p.R130S prestin variant in DFNB61 hearing loss.The Journal of physiology · 2024Article
- Functional Studies of Deafness-Associated Pendrin and Prestin Variants.International journal of molecular sciences · 2024Article
- Low frequency of SLC26A4 c.919-2A > G variant among patients with nonsyndromic hearing loss in Yunnan of Southwest China.BMC medical genomics · 2024Article
- Mechanism of anion exchange and small-molecule inhibition of pendrin.Nature communications · 2024Article
- Optical measurement of gating pore currents in hypokalemic periodic paralysis model cells.Disease models & mechanisms · 2023Article
- Asymmetric pendrin homodimer reveals its molecular mechanism as anion exchanger.Nature communications · 2023Article
- Prestin's fast motor kinetics is essential for mammalian cochlear amplification.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Selection of Diagnostically Significant Regions of theInternational journal of molecular sciences · 2022Article
- Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility.Nature communications · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Thanks to the advent of rapid DNA sequencing technology and its prevalence, many disease-associated genetic variants are rapidly identified in many genes from patient samples. However, the subsequent effort to experimentally validate and define their pathological roles is extremely slow. Consequently, the pathogenicity of most disease-associated genetic variants is solely speculated in silico, which is no longer deemed compelling. We developed an experimental approach to efficiently quantify the pathogenic effects of disease-associated genetic variants with a focus on SLC26A4, which is essential for normal inner ear function. Alterations of this gene are associated with both syndromic and nonsyndromic hereditary hearing loss with various degrees of severity. We established HEK293T-based stable cell lines that express pendrin missense variants in a doxycycline-dependent manner, and systematically determined their anion transport activities with high accuracy in a 96-well plate format using a high throughput plate reader. Our doxycycline dosage-dependent transport assay objectively distinguishes missense variants that indeed impair the function of pendrin from those that do not (functional variants). We also found that some of these putative missense variants disrupt normal messenger RNA splicing. Our comprehensive experimental approach helps determine the pathogenicity of each pendrin variant, which should guide future efforts to benefit patients.
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