GGTA1

GGTA1 is a gene that encodes the enzyme alpha-1,3-galactosyltransferase, a Golgi-resident glycosyltransferase. The enzyme catalyzes the transfer of galactose from UDP-galactose to the Galβ1-4GlcNAc-R acceptor, producing the Galα1-3Galβ1-4GlcNAc-R epitope, commonly known as the alpha-Gal epitope. This epitope is expressed on glycoproteins and glycolipids of most non-primate mammals and some other species.

In humans and other Catarrhini (Old World monkeys, apes, and humans), GGTA1 is inactivated and does not produce a functional enzyme, so human cells lack the Galα1-3Gal epitope. Humans possess natural anti-Gal antibodies (mainly IgG and IgM), which recognize this epitope and are thought to arise from exposure to gut microbiota expressing similar Gal structures.

GGTA1 has particular significance in xenotransplantation. The Gal epitope is a major xenoantigen that can trigger hyperacute rejection when tissues from Gal-positive animals are transplanted into humans. A key strategy to improve xenograft survival is the knockout or silencing of GGTA1 in donor animals, such as pigs, to eliminate Gal epitopes. Advances in genome editing, including CRISPR/Cas9, have produced GGTA1-knockout animals that show reduced acute rejection responses and improved graft compatibility in research settings.

Overall, GGTA1 plays a central role in glycan biosynthesis and has been a focal point in transplantation research due to its role in generating a dominant human xenoantigen.