Defective C1GALT1C1 causes TNPS

Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1GALT1; MIM:610555) mediates the transfer of Galactose (Gal) from UDP-galactose to single O-linked GalNAc residues (Tn antigens) to form Core 1 structures on glycoproteins. C1GALT1 is active when in complex with the molecular chaperone C1GALT1C1 (aka COSMC; MIM:300611) which assists the folding and/or stability of C1GALT1. Defects in C1GALT1C1 causes somatic Tn polyagglutination syndrome (TNPS; MIM:300622), characterised by the polyagglutination of erythrocytes by naturally occurring anti-Tn antibodies following exposure of the Tn antigen on their surface. Defects in C1GALT1C1 render C1GALT1 inactive and results in the accumulation of the incompletely glycosylated Tn antigen. The Tn antigen is tumour-associated, found in a majority of human carcinomas, and is not normally expressed in peripheral tissues or blood cells (Crew et al. 2008, Ju et al. 2014). C1GALT1 and C1GALT1C1 belong to the CAZy family GT31 (www.cazy.org).

糖蛋白-N-乙酰半乳糖胺3-β-半乳糖基转移酶1（C1GALT1；MIM:610555）介导半乳糖（Gal）从UDP-半乳糖转移到单个O-连接的N-乙酰半乳糖胺残基（Tn抗原），从而在糖蛋白上形成核心1结构。C1GALT1在与分子伴侣C1GALT1C1（又称COSMC；MIM:300611）复合时活性增强，后者有助于C1GALT1的折叠和/或稳定性。C1GALT1C1基因缺陷导致体细胞Tn多凝集综合征（TNPS；MIM:300622），其特征为红细胞被自然发生的抗-Tn抗体多凝集，这是由于Tn抗原在红细胞表面的暴露。C1GALT1C1基因缺陷使C1GALT1失活，导致未完全糖基化的Tn抗原积累。Tn抗原与肿瘤相关，存在于大多数人类癌肿中，通常不在外围组织或血细胞中表达（Crew等，2008年，Ju等，2014年）。C1GALT1和C1GALT1C1属于CAZy家族GT31（www.cazy.org）。