Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT95SQHR)

• DOT Name: Apolipoprotein L3 (APOL3)
• Synonyms: Apolipoprotein L-III; ApoL-III; TNF-inducible protein CG12-1; CG12_1
• Gene Name: APOL3
• Related Disease:
  Hepatitis C virus infection
  Hereditary chronic pancreatitis
  Diabetic kidney disease
• UniProt ID: APOL3_HUMAN
• Pfam ID: PF05461
• Sequence:
  MGLGQGWGWEASCFACLIRSCCQVVTFTFPFGFQGISQSLENVSGYYADARLEVGSTQLR
  TAGSCSHSFKRSFLEKKRFTEEATKYFRERVSPVHLQILLTNNEAWKRFVTAAELPRDEA
  DALYEALKKLRTYAAIEDEYVQQKDEQFREWFLKEFPQVKRKIQESIEKLRALANGIEEV
  HRGCTISNVVSSSTGAASGIMSLAGLVLAPFTAGTSLALTAAGVGLGAASAVTGITTSIV
  EHSYTSSAEAEASRLTATSIDRLKVFKEVMRDITPNLLSLLNNYYEATQTIGSEIRAIRQ
  ARARARLPVTTWRISAGSGGQAERTIAGTTRAVSRGARILSATTSGIFLALDVVNLVYES
  KHLHEGAKSASAEELRRQAQELEENLMELTQIYQRLNPCHTH
• Function: May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles.
• Tissue Specificity: Widely expressed; the highest levels are in prostate, lung and placenta; also detected in kidney, bone marrow, spleen, thymus, spinal cord, adrenal gland, salivary gland, trachea and mammary gland; levels are low in brain, heart, fetal liver, pancreas and testis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[1]
Hereditary chronic pancreatitis	DISF0J1Q	Strong	Genetic Variation	[2]
Diabetic kidney disease	DISJMWEY	Limited	Genetic Variation	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Apolipoprotein L3 (APOL3) increases the Neutropenia ADR of Chlorothiazide.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Apolipoprotein L3 (APOL3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Apolipoprotein L3 (APOL3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein L3 (APOL3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Apolipoprotein L3 (APOL3).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Apolipoprotein L3 (APOL3).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Apolipoprotein L3 (APOL3).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Apolipoprotein L3 (APOL3).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Apolipoprotein L3 (APOL3).	[10]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Apolipoprotein L3 (APOL3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Apolipoprotein L3 (APOL3).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Apolipoprotein L3 (APOL3).	[14]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Apolipoprotein L3 (APOL3).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Apolipoprotein L3 (APOL3).	[9]

References

• [1] Elevated hepatic lipid and interferon stimulated gene expression in HCV GT3 patients relative to non-alcoholic steatohepatitis.Hepatol Int. 2016 Nov;10(6):937-946. doi: 10.1007/s12072-016-9733-6. Epub 2016 May 18.
• [2] Family-based association analysis of 42 hereditary prostate cancer families identifies the Apolipoprotein L3 region on chromosome 22q12 as a risk locus.Hum Mol Genet. 2010 Oct 1;19(19):3852-62. doi: 10.1093/hmg/ddq283. Epub 2010 Jul 14.
• [3] A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy.Nephrol Dial Transplant. 2018 Feb 1;33(2):323-330. doi: 10.1093/ndt/gfw451.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
• [15] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.