Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8ZUXY)

• DOT Name: Apolipoprotein C-IV (APOC4)
• Synonyms: Apo-CIV; ApoC-IV; Apolipoprotein C4
• Gene Name: APOC4
• Related Disease:
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Alzheimer disease
  Fatty liver disease
  Hepatitis C virus infection
  Myocardial infarction
  Coronary heart disease
  Non-insulin dependent diabetes
• UniProt ID: APOC4_HUMAN
• Pfam ID: PF15119
• Sequence:
  MSLLRNRLQALPALCLCVLVLACIGACQPEAQEGTLSPPPKLKMSRWSLVRGRMKELLET
  VVNRTRDGWQWFWSPSTFRGFMQTYYDDHLRDLGPLTKAWFLESKDSLLKKTHSLCPRLV
  CGDKDQG
• Function: May participate in lipoprotein metabolism.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• Reactome Pathway:
  VLDL clearance (R-HSA-8964046)
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  VLDL assembly (R-HSA-8866423)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[5]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein C-IV (APOC4).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Apolipoprotein C-IV (APOC4).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Apolipoprotein C-IV (APOC4).	[9]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Apolipoprotein C-IV (APOC4).	[10]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Apolipoprotein C-IV (APOC4).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Apolipoprotein C-IV (APOC4).	[13]
GW7647	DM9RD0C	Investigative	GW7647 decreases the expression of Apolipoprotein C-IV (APOC4).	[14]
Farnesol	DMV2X1B	Investigative	Farnesol decreases the expression of Apolipoprotein C-IV (APOC4).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Apolipoprotein C-IV (APOC4).	[12]

References

• [1] Diagnostic and prognostic significance of mRNA expressions of apolipoprotein A and C family genes in hepatitis B virus-related hepatocellular carcinoma.J Cell Biochem. 2019 Oct;120(10):18246-18265. doi: 10.1002/jcb.29131. Epub 2019 Jun 18.
• [2] GWAS on family history of Alzheimer's disease.Transl Psychiatry. 2018 May 18;8(1):99. doi: 10.1038/s41398-018-0150-6.
• [3] Expression of apolipoprotein C-IV is regulated by Ku antigen/peroxisome proliferator-activated receptor gamma complex and correlates with liver steatosis.J Hepatol. 2008 Nov;49(5):787-98. doi: 10.1016/j.jhep.2008.06.029. Epub 2008 Sep 7.
• [4] Association of an HDL Apolipoproteomic Score With Coronary Atherosclerosis and Cardiovascular Death.J Am Coll Cardiol. 2019 May 7;73(17):2135-2145. doi: 10.1016/j.jacc.2019.01.073.
• [5] The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.Lipids Health Dis. 2015 Jun 28;14:63. doi: 10.1186/s12944-015-0065-7.
• [6] Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM).Diabetes Metab Res Rev. 2015 Oct;31(7):663-71. doi: 10.1002/dmrr.2630. Epub 2015 Mar 5.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [9] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [10] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [11] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.