A4GALT

A4GALT stands for alpha-1,4-galactosyltransferase, a human gene that encodes the enzyme alpha-1,4-galactosyltransferase. The enzyme catalyzes the transfer of galactose from UDP-galactose to lactosylceramide, producing globotriaosylceramide (Gb3), a glycosphingolipid also known as CD77. Gb3 is expressed on the membranes of many cell types, including erythrocytes and endothelial cells, and it plays a role in glycosphingolipid biosynthesis.

Gb3 serves as a receptor for Shiga toxins produced by certain bacteria and is involved in the biology of the P blood group system, where Gb3-derived structures contribute to P-related antigens. Because A4GALT drives Gb3 production, variations in this gene can influence the presence and distribution of these glycolipids on cell surfaces across tissues.

Genetic variants or loss-of-function changes in A4GALT can lead to altered Gb3 expression and, in rare cases, are associated with the P phenotype, a human blood group variant characterized by abnormal P antigen expression and sometimes anti-P antibodies. Beyond blood group considerations, A4GALT and Gb3 have been studied in infectious disease and cancer contexts due to Gb3’s role as a toxin receptor and as a component of cell surface glycosphingolipids. The gene remains a focus of glycobiology and hematology research, with ongoing interest in how its regulation affects glycosphingolipid composition and pathogen interactions.