Further alterations underlying T1D, including thymic defects leading to excessive TCR diversity and shorter length40, defects in peripheral regulatory mechanisms15,70,71 and altered responses against other autoantigens (e.g (pre)(pro)insulin, IA-2, ZnT8, neoantigens)15,72, combine to surpass the physiological autoimmunity, leading to overt T1D. This evidence concerns the gene PTPRN and type 1 diabetes mellitus.