Such an example can be found in one of the strongest T1D associations, which involves the R620W SNP in PTPN22 (protein tyrosine phosphatase, non-receptor type 22), where the 620W disease-associated variant, derived in an even more conserved context, is a gain-of-function variant, with increased catalytic activity [36]. The gene discussed is PTPN22; the disease is type 1 diabetes mellitus.