The human AMPKγ3 R225W mutation negatively impacts site-1 nucleotide binding and does not enhance basal AMPKγ3-associated activity nor glycogen production in human or mouse skeletal muscle.

The AMPKγ3 R225W mutation does not impact the AMPK-associated activity in human skeletal muscle and the mutation is not linked to glycogen accumulation. The R225W mutation ablates the AMPKγ3-associated activation by AICAR/muscle contractions, presumably due to loss of nucleotide binding in the CBS 1 domain of AMPKγ3.