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Key Publications

The table below is a list of relevant papers all about slc13a5, NaCT, and SLC13A5 Citrate Transporter Disorder. These papers are a good place to start when learning about SLC13A5. Email us at info@tessfoundation.org for a publication if you hit a paywall.

ReferenceModels Key findings
Bainbridge, M. N. et al. Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle. Mol Genet Metab 121, 314–319 (2017).
Patient samples
  • Uses mass spectrometry to analyze human patient samples.
  • Compares metabolite levels in the CSF, plasma, and urine in SLC13A5 Epilepsy patients to control patients. They find significant dysregulation in multiple TCA cycle intermediates (some increased, some decreased).
  • Citrate is about 3 times higher than control patient levels in CSF.
Hardies, K. et al. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain 138, 3238–3250 (2015).Clinical data
Cell culture
  • Identifies new mutations in Slc13a5.
  • Characterizes different types of mutations (Type I and Type II).
  • Type I mutants do not get transported to plasma membrane.
  • Type II mutants get transported to the plasma membrane.
  • Both Type I and Type II mutants have loss of citrate transport.
Henke, C. et al. Disruption of the sodium-dependent citrate transporter SLC13A5 in mice causes alterations in brain citrate levels and neuronal network excitability in the hippocampus. Neurobiology of Disease 143, 105018 (2020).Slc13a5 KO mouse
  • Describes the phenotype of the slc13a5 KO mouse (global KO).
  • KO mice had lower body weight and normal baseline EEG activity.
  • KO mice experienced seizures starting at 7 weeks of age and showed a higher propensity of epileptic episodes in an acute epilepsy model.
  • Protein analysis shows altered pathways (including GABA trafficking and metabolism).
Klotz, J., Porter, B. E., Colas, C., Schlessinger, A. & Pajor, A. M. Mutations in the Na+/Citrate Cotransporter NaCT (SLC13A5) in Pediatric Patients with Epilepsy and Developmental Delay. Mol Med 22, 310–321 (2016).Cell culture
Clinical data
  • Describes the clinical features of patients and determines the effect of mutations in slc13a5 on NaCT protein function.
  • After a normal pregnancy, patients experience seizures within the first week of life. Most patients also have teeth hypoplasia, are generally social and happy, and have limited communication.
  • Each mutation tested led to a loss of citrate transport.
  • Some mutations led to decreased protein expression and some had a complete loss of expression.
Matricardi, S. et al. Neonatal developmental and epileptic encephalopathy due to autosomal recessive variants in SLC13A5 gene. Epilepsia 61, 2474–2485 (2020).Clinical data
  • Provides an overview of SLC13A5 Epilepsy by analyzing information from 14 patients ages 3-24 years old.
  • Seizures decrease in frequency with age but unclear whether the number of seizures decrease or whether seizure control with medication is achieved.
  • Most patients develop severe motor and cognitive impairment, as well as tooth hypoplasia.
Sauer, D. B. et al. Structure and inhibition mechanism of the human citrate transporter NaCT. Nature 591, 157–161 (2021).Human NaCT
  • Describes the cryo-EM structure of human NaCT in complex with citrate or a small-molecule inhibitor.
  • Classifies NaCT mutations into 4 categories with proposed effects (Extended Data Table 2).
Thevenon, J. et al. Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life. The American Journal of Human Genetics 95, 113–120 (2014).Clinical data
In silico protein analysis
  • First paper to describe association of neonatal epilepsy associated with Slc13a5 mutations.
  • Identified mutations are predicted to impact sodium binding.

To learn more about SLC13A5, we encourage you to look for more information using PubMed.

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