ArticleProceedings of the National Academy of Sciences of the United States of America2019
Hearing loss mutations alter the functional properties of human P2X2 receptor channels through distinct mechanisms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Perilymphatic ATP plays a critical role in modulating cochlear function to protect from loud sound induced hearing loss.EBioMedicine · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.Science advances · 2026Article
- 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
- Differential Effects of Hearing Loss Mutations in Homomeric P2X2 and Heteromeric P2X2/3 Receptors.Cells · 2025Article
- The genomic landscape of Ménière's disease: a path to endolymphatic hydrops.BMC genomics · 2024Article
- Purine and purinergic receptors in health and disease.MedComm · 2023Review
- Article
- Purinergic Signalling in the Cochlea.International journal of molecular sciences · 2022Review
- P2X2 receptor subunit interfaces are missense variant hotspots, where mutations tend to increase apparent ATP affinity.British journal of pharmacology · 2022Article
- Purinergic signaling in the peripheral vestibular system.Purinergic signalling · 2022Review
- Generation and characterization of a P2rx2 V60L mouse model for DFNA41.Human molecular genetics · 2021Article
- Update of P2X receptor properties and their pharmacology: IUPHAR Review 30.British journal of pharmacology · 2021Review
- Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei.Journal of tissue engineeringArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of P2X2 receptor channels by extracellular ATP is thought to play important roles in cochlear adaptation to elevated sound levels and protection from overstimulation. Each subunit of a trimeric P2X2 receptor is composed of intracellular N and C termini, a large extracellular domain containing the ATP binding site and 2 transmembrane helices (TM1 and TM2) that form a cation permeable pore. Whole-exome sequencing and linkage analysis have identified 3 hP2X2 receptor mutations (V60L, D273Y, and G353R) that cause dominantly inherited progressive sensorineural hearing loss (DFNA41). Available structures of related P2X receptors suggest that these 3 mutations localize to TM1 (V60L), TM2 (G353R), or the β-sheet linking the TMs to the extracellular ATP binding sites (D273Y). Previous studies have concluded that the V60L and G353R mutants are nonfunctional, whereas the D273Y mutant has yet to be studied. Here, we demonstrate that both V60L and G353R mutations do form functional channels, whereas the D273Y mutation prevents the expression of functional channels on the cell membrane. Our results show that the V60L mutant forms constitutively active channels that are insensitive to ATP or the antagonist suramin, suggesting uncoupling of the pore and the ligand binding domains. In contrast, the G353R mutant can be activated by ATP but exhibits alterations in sensitivity to ATP, inward rectification, and ion selectivity. Collectively, our results demonstrate that the loss of functional P2X2 receptors or distinct alterations of its functional properties lead to noise-induced hearing loss, highlighting the importance of these channels in preserving hearing.
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.