N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase 2 (GCNT2)

N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase 2 (GCNT2) is a glycosyltransferase enzyme that catalyzes the addition of β1,6-linked N-acetylglucosamine to poly-N-lactosamine chains, generating branched glycans known as I antigen determinants. These I-branched glycans play pivotal roles in normal development, immune cell differentiation, cell–cell interactions, and receptor signaling. GCNT2 influences the EMT process and contributes to cancer metastasis, especially in breast cancer, by modifying E-cadherin and affecting cellular adhesion and migration. Its activity is required for conversion of fetal i antigen to adult I antigen in red blood cells and other tissues. Loss-of-function mutations cause congenital cataracts and the rare “ii” blood group phenotype. GCNT2 expression serves as both a functional modulator and biomarker of stemness in hematopoietic malignancies, making it a potential therapeutic target, but inhibition could impact normal physiological glycosylation and blood group antigen expression, presenting safety challenges.

Other names

Glucosaminyl transferase 2I-branching enzymeIi blood group enzymeN-acetylglucosaminyltransferase 2GCNT5NACGT1NAGCT1IGNTN-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferasebeta-1,6-N-acetylglucosaminyltransferase 2Ii blood groupunassigned linkage group 3bA421M1.1bA360O19.2ULG3CCATCTRCT13

Inhibition would block I antigen synthesis and associated glycosylation changes (potential anti-metastatic effect in breast cancer and melanoma). Modulation of TGF-β/GCNT2 signaling may interfere with EMT and cancer progression.