Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1FUV6)

• DOT Name: Plexin domain-containing protein 2 (PLXDC2)
• Synonyms: Tumor endothelial marker 7-related protein
• Gene Name: PLXDC2
• Related Disease:
  Chronic kidney disease
  Chronic renal failure
  Glaucoma/ocular hypertension
  Epithelial ovarian cancer
  OPTN-related open angle glaucoma
  Venous thromboembolism
  Acute myelogenous leukaemia
• UniProt ID: PXDC2_HUMAN
• Pfam ID: PF01437
• Sequence:
  MARFPKADLAAAGVMLLCHFFTDQFQFADGKPGDQILDWQYGVTQAFPHTEEEVEVDSHA
  YSHRWKRNLDFLKAVDTNRASVGQDSPEPRSFTDLLLDDGQDNNTQIEEDTDHNYYISRI
  YGPSDSASRDLWVNIDQMEKDKVKIHGILSNTHRQAARVNLSFDFPFYGHFLREITVATG
  GFIYTGEVVHRMLTATQYIAPLMANFDPSVSRNSTVRYFDNGTALVVQWDHVHLQDNYNL
  GSFTFQATLLMDGRIIFGYKEIPVLVTQISSTNHPVKVGLSDAFVVVHRIQQIPNVRRRT
  IYEYHRVELQMSKITNISAVEMTPLPTCLQFNRCGPCVSSQIGFNCSWCSKLQRCSSGFD
  RHRQDWVDSGCPEESKEKMCENTEPVETSSRTTTTVGATTTQFRVLTTTRRAVTSQFPTS
  LPTEDDTKIALHLKDNGASTDDSAAEKKGGTLHAGLIIGILILVLIVATAILVTVYMYHH
  PTSAASIFFIERRPSRWPAMKFRRGSGHPAYAEVEPVGEKEGFIVSEQC
• Function: May play a role in tumor angiogenesis.
• Tissue Specificity: Expressed in the endothelial cells of the stroma but not in the endothelial cells of normal colonic tissue.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Glaucoma/ocular hypertension	DISLBXBY	Definitive	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
OPTN-related open angle glaucoma	DISDR98A	Strong	Genetic Variation	[2]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Plexin domain-containing protein 2 (PLXDC2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Plexin domain-containing protein 2 (PLXDC2).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[15]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Plexin domain-containing protein 2 (PLXDC2).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Plexin domain-containing protein 2 (PLXDC2).	[20]

References

• [1] Genetic loci associated with renal function measures and chronic kidney disease in children: the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium.Nephrol Dial Transplant. 2016 Feb;31(2):262-9. doi: 10.1093/ndt/gfv342. Epub 2015 Sep 28.
• [2] Genetic Variant Near PLXDC2 Influences the Risk of Primary Open-angle Glaucoma by Increasing Intraocular Pressure in the Japanese Population.J Glaucoma. 2017 Nov;26(11):963-966. doi: 10.1097/IJG.0000000000000790.
• [3] Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics.Oncol Lett. 2018 Jun;15(6):9793-9801. doi: 10.3892/ol.2018.8600. Epub 2018 Apr 27.
• [4] A Genome Wide Association Study on plasma FV levels identified PLXDC2 as a new modifier of the coagulation process.J Thromb Haemost. 2019 Nov;17(11):1808-1814. doi: 10.1111/jth.14562. Epub 2019 Jul 22.
• [5] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [6] 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.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [15] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [16] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.