ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder.American journal of obstetrics and gynecology · 2023Pooled it
- TECTB Variants Reveal Tectorial Membrane Vulnerability in Dominant Non-Syndromic Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Perilymphatic ATP plays a critical role in modulating cochlear function to protect from loud sound induced hearing loss.EBioMedicine · 2026Article
- Upregulation of ATP-purinergic P2×2 receptors in the cochlea over-amplifies hearing sensitivity leading to hyperacusis and attenuation by antagonists.bioRxiv : the preprint server for biology · 2026Article
- Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice.eNeuro · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.Science advances · 2026Article
- P2X4 receptors as the dynamic regulators of auditory sensory cell activity: a potential new mechanism for protecting hearing?Purinergic signalling · 2026Article
- Cochlear Homeostasis in Sensorineural Hearing Loss: Mechanisms, Implications, and Therapeutic Prospects.International journal of molecular sciences · 2025Review
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.bioRxiv : the preprint server for biology · 2025Article
- Single-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness.The Journal of clinical investigation · 2025Article
- Leveraging underrepresented population data improves interpretation of genetic variants associated with hearing loss.Scientific reports · 2025Article
- Subtype-specific structural features of the hearing loss-associated human P2X2 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ThemedRxiv : the preprint server for health sciences · 2025Article
- ATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Differential Effects of Hearing Loss Mutations in Homomeric P2X2 and Heteromeric P2X2/3 Receptors.Cells · 2025Article
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Promotion of Cx26 mutants located in TM4 region for membrane translocation successfully rescued hearing loss.Theranostics · 2025Article
- Auckland hearing science discovery and translation in purinergic signaling and inner ear therapeutics.Journal of the Royal Society of New Zealand · 2025Review
- P2XScience advances · 2024Article
- High-affinity agonism at the P2XNature communications · 2024Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 11 institutions in 4 countries.
Funding
Abstract
Age-related hearing loss and noise-induced hearing loss are major causes of human morbidity. Here we used genetics and functional studies to show that a shared cause of these disorders may be loss of function of the ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) that is expressed in sensory and supporting cells of the cochlea. Genomic analysis of dominantly inherited, progressive sensorineural hearing loss DFNA41 in a six-generation kindred revealed a rare heterozygous allele, P2RX2 c.178G > T (p.V60L), at chr12:133,196,029, which cosegregated with fully penetrant hearing loss in the index family, and also appeared in a second family with the same phenotype. The mutation was absent from more than 7,000 controls. P2RX2 p.V60L abolishes two hallmark features of P2X(2) receptors: ATP-evoked inward current response and ATP-stimulated macropore permeability, measured as loss of ATP-activated FM1-43 fluorescence labeling. Coexpression of mutant and WT P2X(2) receptor subunits significantly reduced ATP-activated membrane permeability. P2RX2-null mice developed severe progressive hearing loss, and their early exposure to continuous moderate noise led to high-frequency hearing loss as young adults. Similarly, among family members heterozygous for P2RX2 p.V60L, noise exposure exacerbated high-frequency hearing loss in young adulthood. Our results suggest that P2X(2) function is required for life-long normal hearing and for protection from exposure to noise.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.