Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAH2JOK)

• DOT Name: POM121 and ZP3 fusion protein (POMZP3)
• Synonyms: POM-ZP3
• Gene Name: POMZP3
• Related Disease: Cone dystrophy
• UniProt ID: POZP3_HUMAN
• Pfam ID: PF00100
• Sequence:
  MVCSPVTLRIAPPDRRFSRSAIPEQIISSTLSSPSSNAPDPCAKETVLSALKEKKKKRTV
  EEEDQIFLDGQENKRSCLVDGLTDASSAFKVPRPGPDTLQFTVDVFHFANDSRNMIYITC
  HLKVTLAEQDPDELNKACSFSKPSNSWFPVEGLADICQCCNKGDCGTPSHSRRQPRVVSQ
  WSTSASL
• Tissue Specificity: Expressed in spleen, thymus, pancreas, testis, ovary, small intestine, colon and lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone dystrophy	DIS7SAZZ	moderate	Biomarker	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	POM121 and ZP3 fusion protein (POMZP3) affects the response to substance of Etoposide.	[10]
Paclitaxel	DMLB81S	Approved	POM121 and ZP3 fusion protein (POMZP3) affects the response to substance of Paclitaxel.	[10]
Mitoxantrone	DMM39BF	Approved	POM121 and ZP3 fusion protein (POMZP3) affects the response to substance of Mitoxantrone.	[10]

8 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 POM121 and ZP3 fusion protein (POMZP3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of POM121 and ZP3 fusion protein (POMZP3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of POM121 and ZP3 fusion protein (POMZP3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of POM121 and ZP3 fusion protein (POMZP3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of POM121 and ZP3 fusion protein (POMZP3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of POM121 and ZP3 fusion protein (POMZP3).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of POM121 and ZP3 fusion protein (POMZP3).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of POM121 and ZP3 fusion protein (POMZP3).	[9]

References

• [1] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [6] 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.
• [7] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.