ArticleScience advances2025
Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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.
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Who cites it
4 citing papers in PubMed.
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Determining the intra-residue correlation of missense variant impact using MAVE scores: implications for the ACMG/AMP PM5 criterion for DNA variant classification.Genome medicine · 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
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Citrate is an essential metabolite playing critical roles in metabolism and as a neuromodulator during cellular differentiation and development. Mutations in the human citrate transporter SLC13A5, highly expressed in neurons, have been associated with a debilitating form of epileptic encephalopathy. In this study, we used deep mutational scanning to reveal the effect of 90% of all possible single missense variants on the structure and function of SLC13A5. Computational analyses and a detailed experimental validation of 38 variants revealed an accuracy of 86% and provided mechanistic interpretations for deleterious mutations, including the effect on protein stability, trafficking, and citrate transport. Analyses of blood citrate concentration from individuals enrolled in the UK Biobank study supported our analyses. The results illustrate an unbiased mutational landscape of the citrate transporter, illuminate mechanisms of pathogenicity, and offer a platform for the analysis of specific variants as well as opportunities for the future development of intervention strategies.
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