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FB2026_02
,
released June 18, 2026
This report describes Niemann-Pick disease, type C2 (NPC2), which is a subtype of Niemann-Pick disease; NPC2 is inherited as an autosomal recessive. The human gene implicated in this disease is NPC2, which encodes a cholesterol-binding protein involved in cholesterol transport between endosomes and lysosomes; the human gene NPC1 acts in the same process. There are eight genes in flies orthologous to human NPC2; two of these, Dmel\Npc2a and Dmel\Npc2b, have been used to model Niemann-Pick disease, type C2. Classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both these Drosophila genes.
A UAS construct with a tagged wild-type human Hsap\NPC2 gene has been introduced into flies, but has not been characterized.
Homozygous amorphic mutations in either Dmel\Npc2a and Dmel\Npc2b are viable and fertile, with no significant sterol distribution abnormality. Animals homozygous for the amorphic mutations in both genes are semi-lethal; surviving adults have a reduced lifespan and show increased cell death in the brain.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Multiple types of Niemann-Pick disease include the classic infantile form (type A; MIM:257200), the visceral form (type B; MIM:607616), and the subacute or juvenile form (type C; MIM:257220 and MIM:607625). [from MIM:257220; 2016.09.09]
Niemann-Pick disease comprises a group of lipid metabolism and lysosomal storage diseases with a wide range of symptoms and variable severity. Abnormal lipid metabolism causes a buildup of harmful amounts of lipids in various organs, primarily the liver, spleen, brain, and bone marrow. Affected organs, symptoms, and treatments vary based on the specific sub-type. However, every type is severe and can shorten a person's life expectancy. [http://www.healthline.com/health/niemann-pick-disease; 2016.09.26]
[NIEMANN-PICK DISEASE, TYPE C2; NPC2](https://omim.org/entry/607625)
[NPC INTRACELLULAR CHOLESTEROL TRANSPORTER 2; NPC2](https://omim.org/entry/601015)
Niemann-Pick type C (NPC) disease is an autosomal recessive lipid storage disorder characterized by progressive neurodegeneration and a highly variable clinical phenotype. Patients with the 'classic' childhood onset type C usually appear normal for 1 or 2 years with symptoms appearing between 2 and 4 years. They gradually develop neurologic abnormalities which are initially manifested by ataxia, grand mal seizures, and loss of previously learned speech. Spasticity is striking and seizures, particularly myoclonic jerks, are common. In the childhood-onset form, death usually occurs at age 5 to 15; adult-onset forms, with slower progression, have also been reported [from MIM:257220; 2016.09.09]
Niemann-Pick disease type C2 is caused by homozygous mutation in the NPC2 gene. Approximately 5% of cases of Niemann-Pick type C are caused by mutations in the NPC2 gene. [from MIM:607625; 2016.09.09]
Niemann-Pick disease type C (NPC) is characterized by defective transport of cholesterol and other lipids inside of cells. Excessive amounts of cholesterol accumulate within the liver and spleen and excessive amounts of other lipids accumulate in the brain (http://nnpdf.org/the-disease/overview/).
NPC2 (NPC intracellular cholesterol transporter 2) encodes a protein containing a lipid recognition domain; it functions in regulating the transport of cholesterol through the late endosomal/lysosomal system, acting in concert with NPC1. [from Gene Cards, NPC2; 2016.09.09]