Accelerating SLC Transporter Research: Streamlining Knowledge and Validated Tools

Abstract

A modern, rational approach to a large class of proteins broadly relevant for pharmacology is enabling both from a postgenomic perspective and for reasons of economy of scale. The international public-private consortia RESOLUTE (https://re-solute.eu/) and REsolution (https://re-solute.eu/resol ution) are generating a systematic functional assignment of each of the 451 different human solute carrier (SLC) proteins and, at the same time, trying to catalog and interpret the associated main genetic variants.

ProteoMutaMetrics: machine learning approaches for solute carrier family 6 mutation pathogenicity prediction

“…Two of these (SLC61, SLC50) are currently all orphans according to the SLC family list from the RESOLUTE knowledgebase. 12,19 …”

“…Two of these (SLC61, SLC50) are currently all orphans according to the SLC family list from the RESOLUTE knowledgebase. 12,19 For the SLC6 family, a satisfactory coverage of the members (17 out of 19) and a fair amount of data points can be observed. In total, 259 mutation data points were retrieved, with 146 benign mutations and 113 pathogenic ones, including 21 different transcripts (Table S2 †).…”

“…How those genetic variants in patients affect the function of SLCs is one of the fundamental questions on which the REsolution IMI consortium (https://re-solute.eu/ resolution) is working on. 12 As a cooperative work with many consortium partners, we focused on the development of mutation effect predictors that can provide a binary classication (pathogenic or benign) for the pathogenicity of mutations at SLCs, more specically for the SLC6 family.…”

Membrane transporters in cell physiology, cancer metabolism and drug response

“…These studies highlight the importance of both metabolic and transporter plasticity to promote survival in dynamic nutrient states. As a result of their key roles in cancer cells, targeting GLUTs, MCTs and many other SLC transporters has been of major interest in recent years, with significant public and private funding deployed to improve understanding of this family ( Wiedmer et al, 2022 ), as well as the development of several small-molecule inhibitors and clinical trials ( Kopitz et al, 2016 ; Olszewski et al, 2022 ; Halford et al, 2023 , see Table 1 ).…”

More Than Pharmacokinetics: Transporters in Clinical Pharmacology

“…Finally, the issue includes several interesting perspectives on transporter research. Notably, Giulio Superti‐Furga and the RESOLUTE consortium team 8 members describe the development of many resources available for research on SLC transporters. Included in the resources are databases and knowledgebases, videos, and open access plasmids and cell lines of SLC transporters.…”