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

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.