Mapping genetic interactions in the SLC Transporter Superfamily.

Transporters mediate and control the flux of molecules across compartmental membranes. The human genome encodes 1500 genes with transport functions, of which the solute carriers (SLCs) form the largest superfamily with more than 450 members. Over 250 different SLCs are expressed in a typical human cell, many exhibiting overlapping expression patterns and substrate specificities. The collective role of these often seemingly redundant transporters in defining cellular outcomes, such as cell survival, remains unclear. Here, we performed pooled combinatorial KO screens to identify genetic interactions between 258 expressed SLCs, and between a subset of SLCs and selected metabolic enzymes under different growth conditions using both CRISPR-Cas12a and -Cas9 double knockout systems in the colorectal carcinoma cell line HCT116. Overall design: Pooled combinatorial KO screens with proliferation read out.