Details of Drug Off-Target (DOT)

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

• DOT Name: PI-PLC X domain-containing protein 3 (PLCXD3)
• Gene Name: PLCXD3
• Related Disease:
  Bipolar disorder
  Creutzfeldt Jacob disease
  Prion disease
• UniProt ID: PLCX3_HUMAN
• Pfam ID: PF00388
• Sequence:
  MASSQGKNELKLADWMATLPESMHSIPLTNLAIPGSHDSFSFYIDEASPVGPEQPETVQN
  FVSVFGTVAKKLMRKWLATQTMNFTGQLGAGIRYFDLRISTKPRDPDNELYFAHGLFSAK
  VNEGLEEINAFLTDHHKEVVFLDFNHFYGMQKYHHEKLVQMLKDIYGNKMCPAIFAQEVS
  LKYLWEKDYQVLVFYHSPVALEVPFLWPGQMMPAPWANTTDPEKLIQFLQASITERRKKG
  SFFISQVVLTPKASTVVKGVASGLRETITERALPAMMQWVRTQKPGESGINIVTADFVEL
  GDFISTVIKLNYVFDEGEANT
• Tissue Specificity: Expressed at highest levels in heart. Also detected in kidney, lung, small intestine and colon. Expressed at very low levels, if any, in leukocytes, thymus and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Genetic Variation	[2]
Prion disease	DISOUMB0	Strong	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 affects the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[4]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PI-PLC X domain-containing protein 3 (PLCXD3).	[12]

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 increases the methylation of PI-PLC X domain-containing protein 3 (PLCXD3).	[10]

References

• [1] Common and rare variant analysis in early-onset bipolar disorder vulnerability.PLoS One. 2014 Aug 11;9(8):e104326. doi: 10.1371/journal.pone.0104326. eCollection 2014.
• [2] Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk.Neurobiol Aging. 2012 Jul;33(7):1487.e21-8. doi: 10.1016/j.neurobiolaging.2011.10.011. Epub 2011 Dec 2.
• [3] Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study.BMC Med Genet. 2016 Apr 7;17:28. doi: 10.1186/s12881-016-0278-2.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] 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.