C1GALT1-specific chaperone 1 (C1GALT1C1)

C1GALT1-specific chaperone 1 (C1GALT1C1, also known as Cosmc) is a type II transmembrane protein residing in the endoplasmic reticulum. It acts as a unique, specific molecular chaperone required for the correct folding, stability, and enzymatic activity of core 1 beta1,3-galactosyltransferase 1 (C1GALT1, T-synthase), which is essential for the biosynthesis of the core-1 O-glycan structure (T antigen) on glycoproteins. Unlike C1GALT1, Cosmc does not possess galactosyltransferase activity itself, but is indispensable for proper O-glycosylation in mucin-type proteins—which is critical for cell-cell interactions, immune functions, platelet production, and kidney development. Loss or mutation in C1GALT1C1 disrupts this process, leading to inherited or acquired glycosylation disorders such as Tn syndrome, atypical hemolytic uremic syndrome (COSMC-CDG), and is implicated in cancer and immune diseases. C1GALT1C1 is increasingly recognized as a potential therapeutic and diagnostic target, though currently only complement inhibition (as with eculizumab) is clinically used for associated conditions.

Other names

CosmcHSPC067MSTP143C38H2-L1C1Gal-T2Core 1 beta3-Gal-T2C1GALT2Core 1 beta1,3-galactosyltransferase 2Core 1 beta3-galactosyltransferase-specific molecular chaperoneAHUS8MST143TNPSC38H2-like protein 1beta 1,3-galactosyltransferase 2

Drugs such as eculizumab act by inhibiting the complement pathway (not directly on C1GALT1C1, but as a treatment in disease context). Experimental restoration of glycosylation via wild-type C1GALT1C1 gene transfection.