SMAD3 and neoplasm: Subsequent functional analysis of four TGFBR1 mutants and five TGFBR2 mutants indicated that half of the TGFBR1 mutants and all five TGFBR2 mutants were loss of function for canonical Smad signalling, and that tumours harbouring TGFβ receptor mutations had reduced PO4-SMAD3 activity (Fig. 4).