Normal Function
The NPC2 gene provides instructions for making a protein that is located inside lysosomes, which are compartments in the cell that digest and recycle materials. The NPC2 protein attaches (binds) to cholesterol. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods. Research suggests that the NPC2 protein plays an important role in moving cholesterol and certain other fats (lipids) out of the lysosomes to other parts of the cell.
Health Conditions Related to Genetic Changes
Niemann-Pick disease
More than 20 mutations in the NPC2 gene have been found to cause Niemann-Pick disease type C2. This type of Niemann-Pick disease is characterized by a buildup of fat within cells that leads to movement problems, neurological impairment, lung and liver disease, and speech and feeding problems. The NPC2 gene mutations that cause Niemann-Pick disease type C2 reduce or eliminate NPC2 protein activity, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells. Because these lipids are not in their proper location in cells, many normal cell functions that require lipids (such as cell membrane formation) are impaired. The accumulation of lipids and the cell dysfunction eventually leads to cell death, causing the tissue and organ damage seen in Niemann-Pick disease type C2.
More About This Health ConditionOther Names for This Gene
- epididymal secretory protein
- HE1
- MGC1333
- Niemann-Pick disease, type C2
- NP-C2
- NPC2_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Chikh K, Vey S, Simonot C, Vanier MT, Millat G. Niemann-Pick type C disease: importance of N-glycosylation sites for function and cellular location of the NPC2 protein. Mol Genet Metab. 2004 Nov;83(3):220-30. doi: 10.1016/j.ymgme.2004.06.013. Citation on PubMed
- Mengel E, Klunemann HH, Lourenco CM, Hendriksz CJ, Sedel F, Walterfang M, Kolb SA. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis. 2013 Oct 17;8:166. doi: 10.1186/1750-1172-8-166. Citation on PubMed or Free article on PubMed Central
- Patterson MC, Mengel E, Wijburg FA, Muller A, Schwierin B, Drevon H, Vanier MT, Pineda M. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis. 2013 Jan 16;8:12. doi: 10.1186/1750-1172-8-12. Erratum In: Orphanet J Rare Dis. 2013;8:73. Citation on PubMed or Free article on PubMed Central
- Sturley SL, Patterson MC, Balch W, Liscum L. The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):83-7. doi: 10.1016/j.bbalip.2004.08.014. Citation on PubMed
- Vanier MT, Millat G. Structure and function of the NPC2 protein. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):14-21. doi: 10.1016/j.bbalip.2004.08.007. Citation on PubMed
- Verot L, Chikh K, Freydiere E, Honore R, Vanier MT, Millat G. Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2. Clin Genet. 2007 Apr;71(4):320-30. doi: 10.1111/j.1399-0004.2007.00782.x. Citation on PubMed
- Xu S, Benoff B, Liou HL, Lobel P, Stock AM. Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease. J Biol Chem. 2007 Aug 10;282(32):23525-31. doi: 10.1074/jbc.M703848200. Epub 2007 Jun 14. Citation on PubMed or Free article on PubMed Central
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