Beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) (B4GALNT2)

Beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) is a glycosyltransferase enzyme that catalyzes the final step in the biosynthesis of the Sd(a) and Cad histo-blood group antigens by adding N-acetylgalactosamine to sialylated galactose residues [1.2.1, 1.3.4]. In the field of xenotransplantation, the porcine B4GALNT2 gene is a major therapeutic target because the glycans it produces are immunogenic xenoantigens recognized by preformed human antibodies, leading to hyperacute or acute vascular rejection [1.1.1, 1.4.1]. To overcome this barrier, B4GALNT2 is frequently inactivated in genetically engineered pigs, often as part of a triple-knockout (TKO) strategy alongside GGTA1 and CMAH [1.4.2, 1.4.5]. Beyond transplantation, B4GALNT2 plays a role in cancer biology, where its expression levels are linked to prognosis in colorectal and breast cancers, and it is being investigated as a gene therapy target for Duchenne muscular dystrophy to induce utrophin expression [1.3.1, 1.5.1]. While no small-molecule drugs currently target the enzyme, its activity is modulated through gene editing technologies like CRISPR/Cas9 and viral-mediated gene delivery [1.4.2, 1.2.5]. A significant challenge in targeting this gene in pigs is the presence of a paralog, B4GALNT2-like, which can provide residual antigenicity if not also inactivated [1.4.3]. The enzyme also influences susceptibility to certain infectious diseases, including avian influenza, by modulating the availability of sialic acid receptors [1.3.1].

Other names

GALGT2Sd(a) synthaseUDP-GalNAc:Neu5Aca2-3Galb-R beta-1,4-N-acetylgalactosaminyltransferaseSda beta-1,4-GalNAc transferaseCad antigen synthase

Gene knockout to eliminate immunogenic xenoantigens in xenotransplantation; Gene overexpression to induce utrophin expression in muscular dystrophy