NUS1 dehydrodolichyl diphosphate synthase subunit (NUS1)

NUS1 dehydrodolichyl diphosphate synthase subunit (also known as NgBR, Nogo-B receptor) is a type I transmembrane protein, encoded by the gene NUS1 located on chromosome 6q22.31. It functions as a subunit of the cis-prenyltransferase enzyme complex, partnering with DHDDS to synthesize dolichol, an obligate lipid carrier required for protein glycosylation in the endoplasmic reticulum. This glycosylation process is critical for the function of many proteins including those involved in neuronal development and function. NUS1 also acts as a specific receptor for Nogo-B, a neural and cardiovascular regulator, and is involved in cholesterol transport from lysosomes. Pathogenic mutations in NUS1 disrupt protein glycosylation, leading to a spectrum of neurological disorders such as congenital disorder of glycosylation, epilepsy, intellectual disability, ataxia, and—more rarely—autism spectrum disorder. Biallelic mutations typically cause more severe phenotypes, while haploinsufficiency is sufficient to cause progressive neurological disease. NUS1 is also implicated in certain cancers, with overexpression in some tumor types associated with poor prognosis. The gene is evolutionarily conserved, and knockout in mice is embryonically lethal, highlighting its essential biological role. Despite its clear importance in glycosylation and neurological disease, there remains limited information on its therapeutic targeting or drug interactions. No specific drugs targeting NUS1 are currently known, and biomarker applications for patient selection are not defined. Safety concerns primarily revolve around the severe developmental and neurological consequences of its dysfunction.

Other names

NgBRNogo-B receptorC6orf68TANGO14MGC7199Nuclear undecaprenyl pyrophosphate synthase 1 homologDehydrodolichyl diphosphate synthase complex subunit NUS1CDG1AAMRD55transport and golgi organization 14 homolog (Drosophila)di-trans,poly-cis-decaprenylcistransferase