ArticleScience signaling2016
Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 54 citations in OpenAlex.
- SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus.Molecular genetics & genomic medicine · 2019Trial
- Arg913Gln of SLC12A3 gene promotes development and progression of end-stage renal disease in Chinese type 2 diabetes mellitus.Molecular and cellular biochemistry · 2018Trial
- Spectrum of dominant Charcot-Marie-Tooth disease due toJournal of neurology, neurosurgery, and psychiatry · 2026Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Article
- Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype.Brain : a journal of neurology · 2023Article
- Novel gene-intergenic fusion involving ubiquitin E3 ligase UBE3C causes distal hereditary motor neuropathy.Brain : a journal of neurology · 2023Article
- Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.Annals of clinical and translational neurology · 2022Article
- Genetic heterogeneity in corpus callosum agenesis.Frontiers in genetics · 2022Review
- Expanding the phenotype ofBMJ case reports · 2021Article
- Cation-coupled chloride cotransporters: chemical insights and disease implications.Trends in chemistry · 2021Review
- Diseases caused by mutations in the NaAmerican journal of physiology. Cell physiology · 2021Review
- Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters.The EMBO journal · 2021Article
- Temporal manipulation of KCC3 expression in juvenile or adult mice suggests irreversible developmental deficit in hereditary motor sensory neuropathy with agenesis of the corpus callosum.American journal of physiology. Cell physiology · 2021Article
- Advances in the development of novel compounds targeting cation-chloride cotransporter physiology.American journal of physiology. Cell physiology · 2021Review
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Report of Two Siblings with Andermann Syndrome.Indian journal of pediatrics · 2020Article
- Osmotic Response of Dorsal Root Ganglion Neurons Expressing Wild-Type and Mutant KCC3 Transporters.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2020Article
- Article
- Modulation of brain cation-ClNature communications · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Using exome sequencing, we identified a de novo mutation (c.2971A>G; T991A) in SLC12A6, the gene encoding the K(+)-Cl(-) cotransporter KCC3, in a patient with an early-onset, progressive, and severe peripheral neuropathy primarily affecting motor neurons. Normally, the WNK kinase-dependent phosphorylation of T(991) tonically inhibits KCC3; however, cell swelling triggers Thr(991) dephosphorylation to activate the transporter and restore cell volume. KCC3 T991A mutation in patient cells abolished Thr(991) phosphorylation, resulted in constitutive KCC3 activity, and compromised cell volume homeostasis. KCC3(T991A/T991A) mutant mice exhibited constitutive KCC3 activity and recapitulated aspects of the clinical, electrophysiological, and histopathological findings of the patient. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration.
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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.