ArticleNeuromolecular medicine2015
The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy.
Article in Neuromolecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 83 citations in OpenAlex.
- Infantile Pain Episodes Associated with Novel Nav1.9 Mutations in Familial Episodic Pain Syndrome in Japanese Families.PloS one · 2016Trial
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- NaBrain communications · 2026Article
- Article
- In Vivo Confocal Microscopy of the Cornea in Diagnosing Small Fibre Neuropathy: A Cross-Sectional Observational Study.Diagnostics (Basel, Switzerland) · 2025Article
- Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.The Journal of general physiology · 2025Article
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.Channels (Austin, Tex.) · 2023Review
- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
- Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies.International journal of molecular sciences · 2023Article
- Article
- Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them.International journal of environmental research and public health · 2021Review
- Mechanical allodynia triggered by cold exposure in mice with the Scn11a p.R222S mutation: a novel model of drug therapy for neuropathic pain related to NaNaunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Archiv : European journal of physiology · 2020Review
- A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane.The Journal of biological chemistry · 2020Article
- Evaluation of molecular inversion probe versus TruSeq® custom methods for targeted next-generation sequencing.PloS one · 2020Article
- Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.Toxins · 2019Review
- A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain.Frontiers in neuroscience · 2019Article
- Voltage-gated sodium channels: (NaThe Journal of physiology · 2018Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Painful small fiber neuropathy is a challenging medical condition with no effective treatment. Non-genetic causes can be identified in one half of the subjects. Gain-of-function variants of sodium channels Nav1.7 and Nav1.8 have recently been associated with painful small fiber neuropathy. More recently, mutations of sodium channel Nav1.9 have been linked to human pain disorders, with two gain-of-function mutations found in patients with painful small fiber neuropathy. Here we report a novel Nav1.9 mutation, a glycine 699 substitution by arginine (G699R) in the domain II S4-S5 linker, identified in a patient with painful small fiber neuropathy. In this study, we assayed the mutant channels by voltage-clamp in superior cervical ganglion neurons, which do not produce endogenous Nav1.8 or Nav1.9 currents, and provide a novel platform where Nav1.9 is expressed at relatively high levels. Voltage-clamp analysis showed that the mutation hyperpolarizes (-10.1 mV) channel activation, depolarizes (+6.3 mV) steady-state fast inactivation, slows deactivation, and enhances ramp responses compared with wild-type Nav1.9 channels. Current-clamp analysis showed that the G699R mutant channels render dorsal root ganglion neurons hyperexcitable, via depolarized resting membrane potential, reduced current threshold and increased evoked firing. These observations show that the domain II S4-S5 linker plays an important role in the gating of Nav1.9 and demonstrates that a mutation in this linker is linked to a common pain disorder.
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.