Details of Disease

Disease Name

Niemann-Pick disease type C

NPC; Niemann Pick Disease Type C

Definition

NPC is a complex lipid storage disease mainly characterized by the accumulation of unesterified cholesterol in the late endosomal/lysosomal compartment.

Disease Hierarchy

DISCPWH9: Autosomal recessive disease

DISKS5FO: Niemann-pick disease

DIS492ZO: Niemann-Pick disease type C

Disease Identifiers

MONDO ID

MONDO_0018982

MESH ID

D052556

UMLS CUI

C0220756

MedGen ID

67399

Orphanet ID

646

SNOMED CT ID

66751000

General Information of Disease (ID: DIS492ZO)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Miglustat	DM5J64S	Approved	Small molecular drug	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 18 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GBA	TT1B5PU	Limited	Biomarker	[2]
RAB9A	TT958S6	Limited	Biomarker	[3]
CD58	TT5KSBY	moderate	Biomarker	[4]
CHIT1	TTDYX6T	moderate	Altered Expression	[5]
IGFBP6	TTLAYV8	moderate	Altered Expression	[6]
LPAR5	TTABCJ6	moderate	Biomarker	[7]
OTC	TT5KIO9	moderate	Biomarker	[8]
S1PR3	TTDYP7I	moderate	Altered Expression	[9]
ST3GAL5	TTVF2BJ	moderate	Genetic Variation	[10]
TMEM97	TT9NXW4	moderate	Altered Expression	[11]
ABCA1	TTJW1GN	Strong	Biomarker	[12]
APP	TTE4KHA	Strong	Biomarker	[13]
BACE1	TTJUNZF	Strong	Biomarker	[14]
FCER2	TTCH6MU	Strong	Altered Expression	[15]
LAMP1	TTC214J	Strong	Biomarker	[16]
LIPA	TTS8T1M	Strong	Therapeutic	[17]
PSMB9	TTOUSTQ	Strong	Biomarker	[18]
SMPD1	TTJTM88	Strong	Biomarker	[19]
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⏷ Show the Full List of 18 DTT(s)

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GBA2	OTOZXG5D	Limited	Biomarker	[2]
NPC2	OTE9UEJC	Limited	Biomarker	[20]
APOBEC3A	OTYO6F5P	moderate	Biomarker	[21]
APOD	OTT77XW8	moderate	Altered Expression	[22]
ARF6	OTVV7KJO	moderate	Biomarker	[23]
ARHGAP42	OTIDSJMK	moderate	Altered Expression	[24]
ARL2BP	OT7REEDA	moderate	Altered Expression	[25]
BSND	OTYWZWPD	moderate	Altered Expression	[25]
CUL9	OTPUCLZT	moderate	Biomarker	[26]
FATE1	OTPYXV64	moderate	Biomarker	[27]
HOXC6	OTBCRAZV	moderate	Altered Expression	[28]
NBEAL2	OTMCAXWR	moderate	Biomarker	[29]
NEGR1	OT57ECW9	moderate	Biomarker	[30]
NEUROG2	OTAEMIGT	moderate	Biomarker	[31]
NLK	OT2LETFS	moderate	Altered Expression	[32]
NPB	OT0U82T3	moderate	Genetic Variation	[33]
OSCP1	OTZ4IFGJ	moderate	Altered Expression	[34]
OTUD4	OT7U62SW	moderate	Posttranslational Modification	[35]
OVOL2	OTFM1GKF	moderate	Biomarker	[36]
RBM3	OTAJ7R31	moderate	Biomarker	[37]
RTRAF	OTJ6NVMW	moderate	Altered Expression	[38]
SCGB3A1	OTIR98RB	moderate	Posttranslational Modification	[35]
SEZ6	OTCD8K5D	moderate	Biomarker	[14]
SEZ6L	OT5Z9CUA	moderate	Biomarker	[14]
SPNS1	OTSJ3BJ2	moderate	Biomarker	[39]
STPG4	OT5K4UFL	moderate	Altered Expression	[40]
TRIM29	OT2DNESG	moderate	Altered Expression	[41]
PDLIM7	OTAZVODU	Strong	Biomarker	[42]
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⏷ Show the Full List of 28 DOT(s)

References

1	Miglustat FDA Label
2	Cytosolic glucosylceramide regulates endolysosomal function in Niemann-Pick type C disease.Neurobiol Dis. 2019 Jul;127:242-252. doi: 10.1016/j.nbd.2019.03.005. Epub 2019 Mar 12.
3	Accumulation of sphingomyelin in Niemann-Pick disease type C cells disrupts Rab9-dependent vesicular trafficking of cholesterol.J Cell Physiol. 2020 Mar;235(3):2300-2309. doi: 10.1002/jcp.29137. Epub 2019 Sep 6.
4	Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in Epstein-Barr-virus-positive nasopharyngeal carcinoma cells.Int J Cancer. 1992 Apr 1;50(6):863-7. doi: 10.1002/ijc.2910500605.
5	Oxysterol/chitotriosidase based selective screening for Niemann-Pick type C in infantile cholestasis syndrome patients.BMC Med Genet. 2019 Jul 11;20(1):123. doi: 10.1186/s12881-019-0857-0.
6	IGFBP-6 plays a role as an oncosuppressor gene in NPC pathogenesis through regulating EGR-1 expression.J Pathol. 2010 Nov;222(3):299-309. doi: 10.1002/path.2735.
7	Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma.J Pathol. 2015 Feb;235(3):456-65. doi: 10.1002/path.4460. Epub 2014 Dec 18.
8	Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King's College Hospital experience.Eur J Pediatr. 2015 Oct;174(10):1387-92. doi: 10.1007/s00431-015-2540-6. Epub 2015 Apr 24.
9	Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.J Pathol. 2017 May;242(1):62-72. doi: 10.1002/path.4879. Epub 2017 Mar 15.
10	Inhibition of GM3 synthase attenuates neuropathology of Niemann-Pick disease Type C. by affecting sphingolipid metabolism.Mol Cells. 2014 Feb;37(2):161-71. doi: 10.14348/molcells.2014.2347. Epub 2014 Feb 19.
11	Reduction of TMEM97 increases NPC1 protein levels and restores cholesterol trafficking in Niemann-pick type C1 disease cells.Hum Mol Genet. 2016 Aug 15;25(16):3588-3599. doi: 10.1093/hmg/ddw204. Epub 2016 Jul 4.
12	Mechanistic convergence and shared therapeutic targets in Niemann-Pick disease.J Inherit Metab Dis. 2020 May;43(3):574-585. doi: 10.1002/jimd.12191. Epub 2019 Dec 5.
13	Loss of amyloid precursor protein exacerbates early inflammation in Niemann-Pick disease type C.J Neuroinflammation. 2019 Dec 17;16(1):269. doi: 10.1186/s12974-019-1663-5.
14	BACE1-cleavage of Sez6 and Sez6L is elevated in Niemann-Pick type C disease mouse brains.PLoS One. 2018 Jul 6;13(7):e0200344. doi: 10.1371/journal.pone.0200344. eCollection 2018.
15	Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas.Am J Pathol. 1992 Apr;140(4):879-87.
16	N-glycome of the Lysosomal Glycocalyx is Altered in Niemann-Pick Type C Disease (NPC) Model Cells.Mol Cell Proteomics. 2018 Apr;17(4):631-642. doi: 10.1074/mcp.RA117.000129. Epub 2018 Jan 24.
17	Thiadiazole carbamates: potent inhibitors of lysosomal acid lipase and potential Niemann-Pick type C disease therapeutics.J Med Chem. 2010 Jul 22;53(14):5281-9. doi: 10.1021/jm100499s.
18	Epstein-Barr virus latent membrane protein 2 effects on epithelial acinus development reveal distinct requirements for the PY and YEEA motifs.J Virol. 2013 Dec;87(24):13803-15. doi: 10.1128/JVI.02203-13. Epub 2013 Oct 9.
19	The impact of biomarkers analysis in the diagnosis of Niemann-Pick C disease and acid sphingomyelinase deficiency.Clin Chim Acta. 2018 Nov;486:387-394. doi: 10.1016/j.cca.2018.08.039. Epub 2018 Aug 25.
20	The characteristics and biological significance of NPC2: Mutation and disease.Mutat Res Rev Mutat Res. 2019 Oct-Dec;782:108284. doi: 10.1016/j.mrrev.2019.108284. Epub 2019 Jul 8.
21	Prevalent somatic BRCA1 mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe.Int J Cancer. 2018 Jan 1;142(1):66-80. doi: 10.1002/ijc.31023. Epub 2017 Sep 30.
22	Apolipoprotein D expression in retinoblastoma.Ophthalmic Res. 2003 Mar-Apr;35(2):111-6. doi: 10.1159/000069130.
23	ARF6-mediated endosome recycling reverses lipid accumulation defects in Niemann-Pick Type C disease.PLoS One. 2009;4(4):e5193. doi: 10.1371/journal.pone.0005193. Epub 2009 Apr 14.
24	ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma.Cancer Med. 2018 Aug;7(8):3862-3874. doi: 10.1002/cam4.1552. Epub 2018 Jun 24.
25	Interplay of Viral Infection, Host Cell Factors and Tumor Microenvironment in the Pathogenesis of Nasopharyngeal Carcinoma.Cancers (Basel). 2018 Apr 4;10(4):106. doi: 10.3390/cancers10040106.
26	Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: a prospective observational study.J Transl Med. 2017 Feb 21;15(1):43. doi: 10.1186/s12967-017-1146-3.
27	Automated microscopy screening for compounds that partially revert cholesterol accumulation in Niemann-Pick C cells.J Lipid Res. 2006 Feb;47(2):284-301. doi: 10.1194/jlr.M500388-JLR200. Epub 2005 Nov 15.
28	HOXC6 Overexpression Is Associated With Ki-67 Expression and Poor Survival in NPC Patients.J Cancer. 2017 Jun 3;8(9):1647-1654. doi: 10.7150/jca.18893. eCollection 2017.
29	The Ratio of C-Reactive Protein/Albumin is a Novel Inflammatory Predictor of Overall Survival in Cisplatin-Based Treated Patients with Metastatic Nasopharyngeal Carcinoma.Dis Markers. 2017;2017:6570808. doi: 10.1155/2017/6570808. Epub 2017 Jun 6.
30	The new obesity-associated protein, neuronal growth regulator 1 (NEGR1), is implicated in Niemann-Pick disease Type C (NPC2)-mediated cholesterol trafficking.Biochem Biophys Res Commun. 2017 Jan 22;482(4):1367-1374. doi: 10.1016/j.bbrc.2016.12.043. Epub 2016 Dec 9.
31	Neurogenin-2-transduced human neural progenitor cells attenuate neonatal hypoxic-ischemic brain injury.Transl Res. 2017 May;183:121-136.e9. doi: 10.1016/j.trsl.2016.12.010. Epub 2016 Dec 29.
32	The effect of EBV on WIF1, NLK, and APC gene methylation and expression in gastric carcinoma and nasopharyngeal cancer.J Med Virol. 2017 Oct;89(10):1844-1851. doi: 10.1002/jmv.24863. Epub 2017 Jul 6.
33	Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?.J Inherit Metab Dis. 2006 Aug;29(4):591. doi: 10.1007/s10545-006-0330-z. Epub 2006 Jun 26.
34	Oxidored-nitro domain containing protein 1 (NOR1) expression suppresses slug/vimentin but not snail in nasopharyngeal carcinoma: Inhibition of EMT in vitro and in vivo in mice.Cancer Lett. 2014 Jun 28;348(1-2):109-18. doi: 10.1016/j.canlet.2014.03.005. Epub 2014 Mar 18.
35	Promoter hypermethylation of high-in-normal 1 gene in primary nasopharyngeal carcinoma.Clin Cancer Res. 2003 Aug 1;9(8):3042-6.
36	OVOL2 in metastasis prevention in NPC.Theranostics. 2018 Mar 8;8(8):2242-2244. doi: 10.7150/thno.25181. eCollection 2018.
37	RNA binding motif protein 3 (RBM3) drives radioresistance in nasopharyngeal carcinoma by reducing apoptosis via the PI3K/AKT/Bcl-2 signaling pathway.Am J Transl Res. 2018 Dec 15;10(12):4130-4140. eCollection 2018.
38	Overexpression of chromosome 14 open reading frame 166 correlates with disease progression and poorer prognosis in human NPC.Tumour Biol. 2015 Sep;36(10):7977-86. doi: 10.1007/s13277-015-3518-8. Epub 2015 May 12.
39	L-leucine and SPNS1 coordinately ameliorate dysfunction of autophagy in mouse and human Niemann-Pick type C disease.Sci Rep. 2017 Nov 21;7(1):15944. doi: 10.1038/s41598-017-15305-9.
40	Downregulation of FoxM1 sensitizes nasopharyngeal carcinoma cells to cisplatin via inhibition of MRN-ATM-mediated DNA repair.BMB Rep. 2019 Mar;52(3):208-213. doi: 10.5483/BMBRep.2019.52.3.249.
41	Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway.Oncotarget. 2016 Mar 22;7(12):13634-50. doi: 10.18632/oncotarget.7215.
42	Targeting Exosomal EBV-LMP1 Transfer and miR-203 Expression via the NF-B Pathway: The Therapeutic Role of Aspirin in NPC.Mol Ther Nucleic Acids. 2019 Sep 6;17:175-184. doi: 10.1016/j.omtn.2019.05.023. Epub 2019 Jun 7.