Here, we identify novel associations between serum urate and low-frequency damaging variants in the urate transporters SLC22A12 and SLC2A9, experimentally validate loss-of-function variants in SLC22A12, and identify candidate residues important for urate binding in SLC2A9. These findings provide new insights into the genetic architecture of serum urate and gout, and highlight attractive molecular targets in SLC22A12 and SLC2A9 for lowering of serum urate and prevention of gout. This evidence concerns the gene SLC2A9 and gout.