Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGJ4X9N)

• DOT Name: Apolipoprotein L domain-containing protein 1 (APOLD1)
• Synonyms: Vascular early response gene protein
• Gene Name: APOLD1
• Related Disease:
  Cardiovascular disease
  Prostate carcinoma
  Testicular germ cell tumor
• UniProt ID: APLD1_HUMAN
• Pfam ID: PF05461
• Sequence:
  MFRAPCHRLRARGTRKARAGAWRGCTFPCLGKGMERPAAREPHGPDALRRFQGLLLDRRG
  RLHGQVLRLREVARRLERLRRRSLVANVAGSSLSATGALAAIVGLSLSPVTLGTSLLVSA
  VGLGVATAGGAVTITSDLSLIFCNSRELRRVQEIAATCQDQMREILSCLEFFCRWQGCGD
  RQLLQCGRNASIALYNSVYFIVFFGSRGFLIPRRAEGDTKVSQAVLKAKIQKLAESLESC
  TGALDELSEQLESRVQLCTKSSRGHDLKISADQRAGLFF
• Function: May be involved in angiogenesis. May play a role in activity-dependent changes of brain vasculature. May affect blood-brain permeability.
• Tissue Specificity: Expressed in neonatal dermal microvascular endothelial cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[2]
Testicular germ cell tumor	DIS5RN24	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Apolipoprotein L domain-containing protein 1 (APOLD1).	[16]

3 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 L domain-containing protein 1 (APOLD1).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Apolipoprotein L domain-containing protein 1 (APOLD1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Apolipoprotein L domain-containing protein 1 (APOLD1).	[15]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population.Nat Commun. 2019 Sep 27;10(1):4422. doi: 10.1038/s41467-019-12267-6.
• [3] Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.Br J Cancer. 2010 Jan 19;102(2):419-27. doi: 10.1038/sj.bjc.6605505. Epub 2010 Jan 5.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.