Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFW880A)

• DOT Name: Synaptic plasticity regulator PANTS (C22ORF39)
• Synonyms: Plasticity-associated neural transcript short
• Gene Name: C22ORF39
• UniProt ID: CV039_HUMAN
• Pfam ID: PF11326
• Sequence:
  MADGSGWQPPRPCEAYRAEWKLCRSARHFLHHYYVHGERPACEQWQRDLASCRDWEERRN
  AEAQQSLCESERARVRAARKHILVWAPRQSPPPDWHLPLPQEKDE
• Function: Negatively regulates long-term potentiation and modulates adult synaptic plasticity. Stabilizes the interaction of RTN4 isoform A/Nogo-A with its receptors, inhibiting clustering of postsynaptic AMPA receptors at synaptic sites. Upon neuronal stimulation, degraded at synapses, reducing RTN4 signaling and allowing AMPA receptor clustering at individual synapses.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Synaptic plasticity regulator PANTS (C22ORF39).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synaptic plasticity regulator PANTS (C22ORF39).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptic plasticity regulator PANTS (C22ORF39).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Synaptic plasticity regulator PANTS (C22ORF39).	[5]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Synaptic plasticity regulator PANTS (C22ORF39).	[6]

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 affects the methylation of Synaptic plasticity regulator PANTS (C22ORF39).	[3]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.