Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE9UEJC)

• DOT Name: NPC intracellular cholesterol transporter 2 (NPC2)
• Synonyms: Epididymal secretory protein E1; Human epididymis-specific protein 1; He1; Niemann-Pick disease type C2 protein
• Gene Name: NPC2
• Related Disease:
  Cerebellar degeneration
  Metabolic disorder
  Niemann-Pick disease, type C2
  Non-insulin dependent diabetes
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Carcinoma of liver and intrahepatic biliary tract
  Clear cell renal carcinoma
  Lipoid proteinosis
  Liver cancer
  Liver cirrhosis
  Liver failure
  Lysosomal lipid storage disorder
  Lysosomal storage disease
  Melanoma
  Nasopharyngeal carcinoma
  Niemann-pick disease
  Niemann-Pick disease, type C1
  Parkinson disease
  Progressive supranuclear palsy
  Pulmonary disease
  Renal cell carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Hydrops fetalis
  Tangier disease
  Niemann-Pick disease type C, adult neurologic onset
  Niemann-Pick disease type C, juvenile neurologic onset
  Niemann-Pick disease type C, late infantile neurologic onset
  Niemann-Pick disease type C, severe early infantile neurologic onset
  Niemann-Pick disease type C, severe perinatal form
  Dementia
  Dystonia
  Hepatocellular carcinoma
  Nervous system disease
  Niemann-Pick disease type C
  Rheumatoid arthritis
  Sandhoff disease
• UniProt ID: NPC2_HUMAN
• PDB ID: 5KWY; 6W5V
• Pfam ID: PF02221
• Sequence:
  MRFLAATFLLLALSTAAQAEPVQFKDCGSVDGVIKEVNVSPCPTQPCQLSKGQSYSVNVT
  FTSNIQSKSSKAVVHGILMGVPVPFPIPEPDGCKSGINCPIQKDKTYSYLNKLPVKSEYP
  SIKLVVEWQLQDDKNQSLFCWEIPVQIVSHL
• Function: Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment. Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1. May bind and mobilize cholesterol that is associated with membranes. NPC2 binds cholesterol with a 1:1 stoichiometry. Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport.
• Tissue Specificity: Detected in gallbladder bile . Detected in fibroblasts, kidney, liver, spleen, small intestine, placenta and testis (at protein level) . Epididymis.
• KEGG Pathway:
  Lysosome (hsa04142)
  Cholesterol metabolism (hsa04979)
• Reactome Pathway:
  LDL clearance (R-HSA-8964038)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar degeneration	DISPBCM3	Definitive	Biomarker	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Niemann-Pick disease, type C2	DISLYVZZ	Definitive	Autosomal recessive	[3]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Lipoid proteinosis	DISHAODY	Strong	Biomarker	[7]
Liver cancer	DISDE4BI	Strong	Biomarker	[6]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[4]
Liver failure	DISLGEL6	Strong	Genetic Variation	[8]
Lysosomal lipid storage disorder	DISXQRTX	Strong	Genetic Variation	[9]
Lysosomal storage disease	DIS6QM6U	Strong	Genetic Variation	[10]
Melanoma	DIS1RRCY	Strong	Biomarker	[11]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[12]
Niemann-pick disease	DISKS5FO	Strong	Genetic Variation	[13]
Niemann-Pick disease, type C1	DIS9HUE3	Strong	Genetic Variation	[14]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[15]
Progressive supranuclear palsy	DISO5KRQ	Strong	Genetic Variation	[15]
Pulmonary disease	DIS6060I	Strong	Biomarker	[16]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[17]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[17]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[17]
Hydrops fetalis	DISD9BBF	moderate	Genetic Variation	[18]
Tangier disease	DIS57P0M	moderate	Biomarker	[19]
Niemann-Pick disease type C, adult neurologic onset	DISVQ9PR	Supportive	Autosomal recessive	[20]
Niemann-Pick disease type C, juvenile neurologic onset	DISBAITH	Supportive	Autosomal recessive	[20]
Niemann-Pick disease type C, late infantile neurologic onset	DISOO4DE	Supportive	Autosomal recessive	[20]
Niemann-Pick disease type C, severe early infantile neurologic onset	DISK3V8S	Supportive	Autosomal recessive	[20]
Niemann-Pick disease type C, severe perinatal form	DISOIE66	Supportive	Autosomal recessive	[20]
Dementia	DISXL1WY	Limited	Genetic Variation	[21]
Dystonia	DISJLFGW	Limited	Biomarker	[22]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[23]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[24]
Niemann-Pick disease type C	DIS492ZO	Limited	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[25]
Sandhoff disease	DISELKA4	Limited	Biomarker	[26]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of NPC intracellular cholesterol transporter 2 (NPC2).	[27]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[30]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[29]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[31]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[32]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[33]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[34]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[28]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[35]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[38]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of NPC intracellular cholesterol transporter 2 (NPC2).	[39]

References

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