Details of Drug Off-Target (DOT)

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

• DOT Name: Apolipoprotein L6 (APOL6)
• Synonyms: Apolipoprotein L-VI; ApoL-VI
• Gene Name: APOL6
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Cardiovascular disease
  Influenza
  Rheumatoid arthritis
• UniProt ID: APOL6_HUMAN
• Pfam ID: PF05461
• Sequence:
  MDNQAERESEAGVGLQRDEDDAPLCEDVELQDGDLSPEEKIFLREFPRLKEDLKGNIDKL
  RALADDIDKTHKKFTKANMVATSTAVISGVMSLLGLALAPATGGGSLLLSTAGQGLATAA
  GVTSIVSGTLERSKNKEAQARAEDILPTYDQEDREDEEEKADYVTAAGKIIYNLRNTLKY
  AKKNVRAFWKLRANPRLANATKRLLTTGQVSSRSRVQVQKAFAGTTLAMTKNARVLGGVM
  SAFSLGYDLATLSKEWKHLKEGARTKFAEELRAKALELERKLTELTQLYKSLQQKVRSRA
  RGVGKDLTGTCETEAYWKELREHVWMWLWLCVCLCVCVYVQFT
• Function: May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles.
• Tissue Specificity: Widely expressed; highly expressed in the uterus, fetal brain and spinal cord, also detected in heart, liver, lung, colon, spleen, thymus, prostate, placenta, adrenal gland, salivary and mammary gland.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]
Influenza	DIS3PNU3	Strong	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Disputed	Genetic Variation	[3]

9 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 L6 (APOL6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Apolipoprotein L6 (APOL6).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein L6 (APOL6).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Apolipoprotein L6 (APOL6).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Apolipoprotein L6 (APOL6).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Apolipoprotein L6 (APOL6).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Apolipoprotein L6 (APOL6).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Apolipoprotein L6 (APOL6).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Apolipoprotein L6 (APOL6).	[13]

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 L6 (APOL6).	[9]

References

• [1] Apolipoprotein L6, induced in atherosclerotic lesions, promotes apoptosis and blocks Beclin 1-dependent autophagy in atherosclerotic cells.J Biol Chem. 2011 Aug 5;286(31):27389-98. doi: 10.1074/jbc.M110.210245. Epub 2011 Jun 6.
• [2] A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
• [3] Identification of pathogenic genes related to rheumatoid arthritis through integrated analysis of DNA methylation and gene expression profiling.Gene. 2017 Nov 15;634:62-67. doi: 10.1016/j.gene.2017.08.032. Epub 2017 Sep 4.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.