Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT303Q7B)

• DOT Name: Apolipoprotein L2 (APOL2)
• Synonyms: Apolipoprotein L-II; ApoL-II
• Gene Name: APOL2
• Related Disease:
  Cocaine addiction
  Irritable bowel syndrome
  Pleuropulmonary blastoma
  Schizophrenia
• UniProt ID: APOL2_HUMAN
• PDB ID: 7LF8
• Pfam ID: PF05461
• Sequence:
  MNPESSIFIEDYLKYFQDQVSRENLLQLLTDDEAWNGFVAAAELPRDEADELRKALNKLA
  SHMVMKDKNRHDKDQQHRQWFLKEFPRLKRELEDHIRKLRALAEEVEQVHRGTTIANVVS
  NSVGTTSGILTLLGLGLAPFTEGISFVLLDTGMGLGAAAAVAGITCSVVELVNKLRARAQ
  ARNLDQSGTNVAKVMKEFVGGNTPNVLTLVDNWYQVTQGIGRNIRAIRRARANPQLGAYA
  PPPHVIGRISAEGGEQVERVVEGPAQAMSRGTMIVGAATGGILLLLDVVSLAYESKHLLE
  GAKSESAEELKKRAQELEGKLNFLTKIHEMLQPGQDQ
• 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 found in lung, thymus, pancreas, placenta, adult brain and prostate; also detected in spleen, liver, kidney, colon, small intestine, uterus, spinal cord, adrenal gland, salivary gland, trachea, mammary gland, skeletal muscle, testis and fetal brain and liver.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cocaine addiction	DISHTRXG	Strong	Biomarker	[1]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[2]
Pleuropulmonary blastoma	DIS3UCS9	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	No Known	Autosomal dominant	[4]

12 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 Apolipoprotein L2 (APOL2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein L2 (APOL2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Apolipoprotein L2 (APOL2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Apolipoprotein L2 (APOL2).	[8]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Apolipoprotein L2 (APOL2).	[1]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Apolipoprotein L2 (APOL2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Apolipoprotein L2 (APOL2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Apolipoprotein L2 (APOL2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Apolipoprotein L2 (APOL2).	[13]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Apolipoprotein L2 (APOL2).	[14]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Apolipoprotein L2 (APOL2).	[1]
Manganese	DMKT129	Investigative	Manganese increases the expression of Apolipoprotein L2 (APOL2).	[15]

References

• [1] Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2006 Dec 27;1(1):e114. doi: 10.1371/journal.pone.0000114.
• [2] Gene expression profiles in peripheral blood mononuclear cells correlate with salience network activity in chronic visceral pain: A pilot study.Neurogastroenterol Motil. 2017 Jun;29(6):10.1111/nmo.13027. doi: 10.1111/nmo.13027. Epub 2017 Feb 12.
• [3] Lichen planopilaris and pseudopelade of Brocq involve distinct disease associated gene expression patterns by microarray.J Dermatol Sci. 2010 Jan;57(1):27-36. doi: 10.1016/j.jdermsci.2009.10.011. Epub 2009 Nov 22.
• [4] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2006 Dec 27;1(1):e114. doi: 10.1371/journal.pone.0000114.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
• [15] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.