ArticleFrontiers in neuroscience2019
A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain.
Article in Frontiers in neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Deeper delving Nav1.8 inhibitor Suzetrigine in chronic pain.Acta pharmacologica Sinica · 2026Article
- Mechanism-based nonopioid analgesic targets.The Journal of clinical investigation · 2025Review
- A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaScience advances · 2025Article
- Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.Biomolecules · 2025Review
- Article
- Article
- 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
- The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.Biophysical journal · 2022Article
- Familial episodic pain syndrome: a case report and literature review.Annals of translational medicine · 2022Article
- Familial Episodic Pain Syndromes.Journal of pain research · 2022Review
- The Gain-of-Function R222S Variant inFrontiers in neurology · 2022Article
- Contributions of NaScientific reports · 2021Article
- Mathematical Modeling of Ion Quantum Tunneling Reveals Novel Properties of Voltage-Gated Channels and Quantum Aspects of Their Pathophysiology in Excitability-Related Disorders.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Article
- 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
- The development of somatosensory neurons: Insights into pain and itch.Current topics in developmental biology · 2021Review
- Neuropathic Itch.Cells · 2020Review
- Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Archiv : European journal of physiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Voltage-gated sodium channel Nav1.9 is a threshold channel that regulates action potential firing. Nav1.9 is preferentially expressed in myenteric neurons, and small-diameter dorsal root ganglion (DRG) and trigeminal ganglion neurons including nociceptors. Recent studies have demonstrated a monogenic Mendelian link of Nav1.9 to human pain disorders. Gain-of-function variants in Nav1.9, which cause smaller depolarizations of RMP, have been identified in patients with familial episodic pain type 3 (FEPS3) and the more common pain disorder small fiber neuropathy. To explore the phenotypic spectrum of Nav1.9 channelopathy, here we report a new Nav1.9 mutation, N816K, in a child with early-onset episodic pain in both legs, episodic abdominal pain, and chronic constipation. Sequencing of further selected pain genes was normal. N816K alters a residue at the N-terminus of loop 2, proximal to the cytoplasmic terminus of transmembrane segment 6 in domain II. Voltage-clamp recordings demonstrate that Nav1.9-N816K significantly increases current density and hyperpolarizes voltage-dependence of activation by 10 mV, enabling a larger window current. Current-clamp recordings in DRG neurons shows that N816K channels depolarize RMP of small DRG neurons by 7 mV, reduce current threshold of firing an action potential and render DRG neurons hyperexcitable. Taken together these data demonstrate gain-of-function attributes of the newly described N816K mutation at the channel and cellular levels, which are consistent with a pain phenotype in the carrier of this mutation.
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.