ST6GALNAC4 Gene - Function, Expression, and Disease Associations

ST6GALNAC4 encodes a Golgi membrane-bound sialyltransferase that catalyzes the transfer of sialic acid from CMP-sialic acid to N-acetylgalactosamine (GalNAc) residues on glycoproteins and glycolipids, forming the sialyl-Tn (STn) antigen (Neu5Acα2-6GalNAcα1-O-Ser/Thr). This enzyme is a member of the ST6GalNAc family and plays a critical role in O-glycan biosynthesis, particularly in cancer-associated aberrant glycosylation. The sialyl-Tn antigen is a well-known tumor-associated carbohydrate antigen expressed in various carcinomas and is linked to poor prognosis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG: Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)

• KEGG: Mucin type O-glycan biosynthesis (hsa00512)

• Reactome: O-linked glycosylation (R-HSA-5173105)

ST6GALNAC4 is a type II transmembrane protein localized to the Golgi apparatus. It contains a short N-terminal cytoplasmic tail, a transmembrane domain, and a large C-terminal catalytic domain facing the Golgi lumen. The enzyme specifically adds sialic acid in an α2-6 linkage to GalNAc residues on O-glycans, generating the sialyl-Tn epitope. This modification is often upregulated in cancer and contributes to tumor progression, immune evasion, and metastasis. The protein is encoded by 9 exons and has a molecular weight of approximately 40 kDa.