NPC1
MIM.607623 18q11-q12
The gene NPC1 encodes a protein involved in cholesterol trafficking; therefore, in this disorder, cholesterol accumulates in the affected cells.
The NPC1 gene encodes a 1,278-amino acid protein with sequence similarity to the morphogen receptor ’patched’ (MIM.601309), which is mutant in the basal cell nevus syndrome (BCNS) (MIM.109400), and to the putative sterol-sensing regions of SREBP cleavage-activating protein (MIM.601510) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (MIM.142910).
In the brain, NPC1 is present in astrocytic processes in close apposition to nerve terminals. With defective cholesterol trafficking, terminal axons and dendrites degenerate. NPC is clinically very heterogeneous.