By incorporating this critical residue for the phospho-tyrosine binding function of SH2 domains into ReKINect, we could predict 20 distinct instances (including mutations on ABL, SYK, and GRB10) where cancer mutations disrupt a critical functional residue, thus impairing the ability of the mutant SH2 domains to bind their substrates (Table S7). The gene discussed is SYK; the disease is cancer.