ArticleMolecular medicine (Cambridge, Mass.)2016
Mutations in the Na(+)/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay.
Article in Molecular medicine (Cambridge, Mass.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 50 papers.
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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.
SLC13A5 Deficiency: a Prospective Natural History Study - Remote Only (International)
SLC13A5 Deficiency: A Prospective Natural History Study - United States Only
Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Structures of the human sodium-citrate cotransporter NaCT with and without substrates.Structure (London, England : 1993) · 2026Article
- Citrate Transporter NaCT and Enamel Mineralization: TheInternational journal of molecular sciences · 2026Article
- Structures of the human sodium-citrate cotransporter NaCT with and without substrates.bioRxiv : the preprint server for biology · 2026Article
- Functional role of a structural water in the elevator domain of dicarboxylate transporter VcINDY.PNAS nexus · 2026Article
- AAV-mediated gene therapy in a model of SLC13A5 citrate transporter disorder rescues epileptic and metabolic phenotypes.The Journal of clinical investigation · 2026Article
- Potential Biological Processes Related to Brain SLC13A5 Across the Lifespan: Weighted Gene Co-Expression Network Analysis from Large Human Transcriptomic Data.Brain sciences · 2026Article
- Regulatory interaction between metabolite transporters coordinates glucose and exometabolite fluxes to drive bioenergetics.Nature communications · 2025Article
- Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5.Science advances · 2025Article
- Modulation of NMDA receptor signaling and zinc chelation prevent seizure-like events in a zebrafish model of SLC13A5 epilepsy.PLoS biology · 2025Article
- Unraveling neuroimaging insights in developmental epileptic encephalopathy type 25: a comprehensive review of reported cases and a novel SLC13A5 variant.Acta neurologica Belgica · 2024Review
- Molecular Phenotypes Segregate Missense Mutations in SLC13A5 Epilepsy.Journal of molecular biology · 2024Article
- Article
- Novel Approaches to Studying SLC13A5 Disease.Metabolites · 2024Review
- Sis2 regulates yeast replicative lifespan in a dose-dependent manner.Nature communications · 2023Article
- Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders.Molecular and cellular biochemistry · 2023Review
- Mapping the Metabolic Niche of Citrate Metabolism andMetabolites · 2023Review
- Characterizing a rare neurogenetic disease, SLC13A5 citrate transporter disorder, utilizing clinical data in a cloud-based medical record collection system.Frontiers in genetics · 2023Article
- Review
- Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain.International journal of molecular sciences · 2022Review
- Carbamazepine efficacy in a severe electro-clinical presentation of SLC13A5-epilepsy.Annals of clinical and translational neurology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the SLC13A5 gene that codes for the Na(+)/citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia in children. In the present study we identify additional SLC13A5 mutations in nine epilepsy patients from six families. To better characterize the syndrome, families with affected children answered questions about the scope of illness and treatment strategies. There are currently no effective treatments, but some anti-epileptic drugs targeting the GABA system reduce seizure frequency. Acetazolamide, a carbonic anhydrase inhibitor and atypical anti-seizure medication decreases seizures in 4 patients. In contrast to previous reports, the ketogenic diet and fasting produce worsening of symptoms. The effects of the mutations on NaCT transport function and protein expression were examined by transient transfections of COS-7 cells. There was no transport activity from any of the mutant transporters, although some of the mutant transporter proteins were present on the plasma membrane. The structural model of NaCT suggests that these mutations can affect helix packing or substrate binding. We tested various treatments, including chemical chaperones and low temperatures, but none improve transport function in the NaCT mutants. Interestingly, coexpression of NaCT and the mutants results in decreased protein expression and activity of the wild-type transporter, indicating functional interaction. In conclusion, our study has identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na(+)/citrate transporters.
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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.