ST8SIA5 Gene: Function, Expression, Mutations & Disease | Biomedical SEO

ST8SIA5 encodes a member of the glycosyltransferase family 29, specifically an alpha-2,8-sialyltransferase. This enzyme catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to form GD3, a key step in the biosynthesis of b- and c-series gangliosides. Gangliosides are sialic acid-containing glycosphingolipids abundant in the nervous system and involved in cell-cell recognition, adhesion, and signaling. ST8SIA5 is predominantly expressed in brain and plays a critical role in neural development, differentiation, and plasticity. Aberrant expression and mutations have been linked to neurodevelopmental disorders and various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Ganglioside biosynthesis (b-series) - Reactome R-HSA-1660662

• Sphingolipid metabolism - KEGG hsa00600

• Glycosphingolipid biosynthesis - KEGG hsa00603

ST8SIA5 is a 359-amino acid 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 a sialic acid residue in alpha-2,8 linkage to GM3 to produce GD3. GD3 is a precursor for b- and c-series gangliosides, which are critical for neural development, cell differentiation, and tumor progression. Structural studies indicate that the catalytic domain adopts a GT-A fold typical of glycosyltransferases, with a conserved DXD motif essential for metal ion coordination and substrate binding.