Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport.

•IgG1 modified to reduce cytotoxicity (G1Δnab) has impaired FcRn-mediated function.•G1Δnab variants bind FcRn in a pH-dependent manner but with altered kinetics.•G1Δnab variants are transported to a lesser degree across polarized cells and placenta.•Data collectively point to residues originating from IgG2 affecting IgG transport.