ArticleHuman mutation2010
Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations.
Article in Human mutation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 125 citations in OpenAlex.
- SCN9A Variants May be Implicated in Neuropathic Pain Associated With Diabetic Peripheral Neuropathy and Pain Severity.The Clinical journal of pain · 2015Trial
- Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain.International journal of molecular sciences · 2026Review
- Botulinum toxin type A attenuates trigeminal neuralgia-like pain by suppressing CGRP release and modulating NaV1.7-associated signaling.The journal of headache and pain · 2026Article
- Structural basis for inhibition of the voltage-gated sodium channel NaThe Journal of biological chemistry · 2026Article
- Co-Occurrence ofCase reports in medicine · 2026Article
- Tetrodotoxin: The State-of-the-Art Progress in Characterization, Detection, Biosynthesis, and Transport Enrichment.Marine drugs · 2024Review
- Article
- Homozygosity for a RareInternational journal of molecular sciences · 2024Article
- The pain target NaPflugers Archiv : European journal of physiology · 2024Article
- A Systematic Review of Congenital Insensitivity to Pain, a Rare Disease.Journal of personalized medicine · 2024Review
- Association of respiratory failure with inhibition of NaV1.6 in the phrenic nerve.Channels (Austin, Tex.) · 2022Article
- Ocular manifestations among patients with congenital insensitivity to pain due to variants in PRDM12 and SCN9A genes.American journal of medical genetics. Part A · 2022Article
- Voltage-dependent CaPflugers Archiv : European journal of physiology · 2022Review
- Clinical and Functional Features of Epilepsy-Associated In-Frame Deletion Variants inFrontiers in molecular neuroscience · 2022Article
- Sickle cell disease chronic joint pain: Clinical assessment based on maladaptive central nervous system plasticity.Frontiers in medicine · 2022Review
- Selective Targeting of Nav1.7 with Engineered Spider Venom-Based Peptides.Channels (Austin, Tex.) · 2021Review
- Uncoupling sodium channel dimers restores the phenotype of a pain-linked NaBritish journal of pharmacology · 2020Article
- Two Novel Peptide Toxins from the SpiderToxins · 2020Article
- Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Archiv : European journal of physiology · 2020Review
- Physiology and Pathophysiology of Itch.Physiological reviews · 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
12 authors at 6 institutions in 4 countries.
Funding
Abstract
SCN9Aencodes the voltage-gated sodium channel Na(v)1.7, a protein highly expressed in pain-sensing neurons. Mutations in SCN9A cause three human pain disorders: bi-allelic loss of function mutations result in Channelopathy-associated Insensitivity to Pain (CIP), whereas activating mutations cause severe episodic pain in Paroxysmal Extreme Pain Disorder (PEPD) and Primary Erythermalgia (PE). To date, all mutations in SCN9A that cause a complete inability to experience pain are protein truncating and presumably lead to no protein being produced. Here, we describe the identification and functional characterization of two novel non-truncating mutations in families with CIP: a homozygously-inherited missense mutation found in a consanguineous Israeli Bedouin family (Na(v)1.7-R896Q) and a five amino acid in-frame deletion found in a sporadic compound heterozygote (Na(v)1.7-DeltaR1370-L1374). Both of these mutations map to the pore region of the Na(v)1.7 sodium channel. Using transient transfection of PC12 cells we found a significant reduction in membrane localization of the mutant protein compared to the wild type. Furthermore, voltage clamp experiments of mutant-transfected HEK293 cells show a complete loss of function of the sodium channel, consistent with the absence of pain phenotype. In summary, this study has identified critical amino acids needed for the normal subcellular localization and function of Na(v)1.7.
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.