A mutation in the 5' untranslated region of the human alpha-galactosidase A gene in high-activity variants inhibits specific protein binding.

Recently, normal individuals were identified who had high levels of plasma alpha-galactosidase A activity and a G to A transition in the 5' untranslated (5' UT) region of the alpha-galactosidase A gene. Electrophoretic mobility shift assays revealed that the wild-type sequence at the site of this mutation complexed with specific nuclear proteins. A standard NF-kappa B site competed with the 5' UT site for formation of these DNA-protein complexes. Complex formation was inhibited by the transition mutation. Therefore, the wild-type site might down-modulate expression of the alpha-galactosidase A gene from this 5' untranslated region, which includes a previously described protein-binding site for another family of sequence-specific DNA-binding proteins, methylated DNA-binding protein.