ArticleNature genetics2013
A de novo gain-of-function mutation in SCN11A causes loss of pain perception.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 302 citations in OpenAlex.
- Migraine, chronic kidney disease and kidney function: observational and genetic analyses.Human genetics · 2023Pooled it
- Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study.PLoS genetics · 2020Pooled it
- Infantile Pain Episodes Associated with Novel Nav1.9 Mutations in Familial Episodic Pain Syndrome in Japanese Families.PloS one · 2016Trial
- Chasing the Wrong Door for 30 Years: Is Suzetrigine the Key to Selective Pain Relief?Medicina (Kaunas, Lithuania) · 2026Review
- Functional and molecular diversity of human C-fibers in pain modulation.Current opinion in supportive and palliative care · 2026Review
- Article
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- 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
- A new era in CAR-NK cell therapy: from technological innovations to clinical applications.World journal of pediatrics : WJP · 2026Review
- Review
- A multi-omic atlas of human autonomic and sensory ganglia implicates cell types in peripheral neuropathies.bioRxiv : the preprint server for biology · 2025Article
- Familial Episodic Pain Syndrome: A Japanese Family Harboring the Novel Variant c.2431C>T (p.Leu811Phe) in SCN11A.Biochemical genetics · 2025Article
- 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
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Article
- Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaPain and therapy · 2025Article
- Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.The Journal of general physiology · 2025Article
- Small-Fiber Neuropathy: An Etiology-Oriented Review.Brain sciences · 2025Review
- Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sensation of pain protects the body from serious injury. Using exome sequencing, we identified a specific de novo missense mutation in SCN11A in individuals with the congenital inability to experience pain who suffer from recurrent tissue damage and severe mutilations. Heterozygous knock-in mice carrying the orthologous mutation showed reduced sensitivity to pain and self-inflicted tissue lesions, recapitulating aspects of the human phenotype. SCN11A encodes Nav1.9, a voltage-gated sodium ion channel that is primarily expressed in nociceptors, which function as key relay stations for the electrical transmission of pain signals from the periphery to the central nervous system. Mutant Nav1.9 channels displayed excessive activity at resting voltages, causing sustained depolarization of nociceptors, impaired generation of action potentials and aberrant synaptic transmission. The gain-of-function mechanism that underlies this channelopathy suggests an alternative way to modulate pain perception.
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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.