Data- and knowledge-derived functional landscape of human solute carriers

Author(s)
Ulrich Goldmann, Tabea Wiedmer, Andrea Garofoli, Vitaly Sedlyarov, Manuel Bichler, Ben Haladik, Gernot Wolf, Eirini Christodoulaki, Alvaro Ingles-Prieto, Evandro Ferrada, Fabian Frommelt, Shao Thing Teoh, Philipp Leippe, Gabriel Onea, Martin Pfeifer, Mariah Kohlbrenner, Lena Chang, Paul Selzer, Jürgen Reinhardt, Daniela Digles, Gerhard F. Ecker, Tanja Osthushenrich, Aidan MacNamara, Anders Malarstig, David Hepworth, Giulio Superti-Furga
Abstract

The human solute carrier (SLC) superfamily of ~460 membrane transporters remains the largest understudied protein family despite its therapeutic potential. To advance SLC research, we developed a comprehensive knowledgebase that integrates systematic multi-omics data sets with selected curated information from public sources. We annotated SLC substrates through literature curation, compiled SLC disease associations using data mining techniques, and determined the subcellular localization of SLCs by combining annotations from public databases with an immunofluorescence imaging approach. This SLC-centric knowledge is made accessible to the scientific community via a web portal featuring interactive dashboards and visualization tools. Utilizing this systematically collected and curated resource, we computationally derived an integrated functional landscape for the entire human SLC superfamily. We identified clusters with distinct properties and established functional distances between transporters. Based on all available data sets and their integration, we assigned biochemical/biological functions to each SLC, making this study one of the largest systematic annotations of human gene function and a potential blueprint for future research endeavors.

Organisation(s)
Department of Microbiology, Immunobiology and Genetics, Department of Pharmaceutical Sciences
External organisation(s)
Research Center for Molecular Medicine of the Austrian Academy of Sciences, St. Anna Children’s Cancer Research Institute, Medizinische Universität Wien, Novartis Pharma AG, Bayer BioScience nv, Pfizer Research and Development, Wyeth, LLC, Fondazione Ri.MED
Journal
Molecular Systems Biology
ISSN
1744-4292
DOI
https://doi.org/10.1038/s44320-025-00108-2
Publication date
2025
Peer reviewed
Yes
Austrian Fields of Science 2012
102004 Bioinformatics, 301207 Pharmaceutical chemistry
Keywords
ASJC Scopus subject areas
Information Systems, General Biochemistry,Genetics and Molecular Biology, General Immunology and Microbiology, General Agricultural and Biological Sciences, Computational Theory and Mathematics, Applied Mathematics
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/b532a380-c413-4fae-9b21-57da832cd9e3