Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8RE3IM)

• DOT Name: RING finger protein 122 (RNF122)
• Gene Name: RNF122
• Related Disease: Attention deficit hyperactivity disorder
• UniProt ID: RN122_HUMAN
• Pfam ID: PF13639
• Sequence:
  MHPFQWCNGCFCGLGLVSTNKSCSMPPISFQDLPLNIYMVIFGTGIFVFMLSLIFCCYFI
  SKLRNQAQSERYGYKEVVLKGDAKKLQLYGQTCAVCLEDFKGKDELGVLPCQHAFHRKCL
  VKWLEVRCVCPMCNKPIASPSEATQNIGILLDELV
• Function: May induce necrosis and apoptosis. May play a role in cell viability.
• Tissue Specificity: Widely expressed in several tissues and cell lines.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RING finger protein 122 (RNF122).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RING finger protein 122 (RNF122).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger protein 122 (RNF122).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of RING finger protein 122 (RNF122).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of RING finger protein 122 (RNF122).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of RING finger protein 122 (RNF122).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RING finger protein 122 (RNF122).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of RING finger protein 122 (RNF122).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RING finger protein 122 (RNF122).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RING finger protein 122 (RNF122).	[11]

References

• [1] Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder.Sci Rep. 2017 Jul 14;7(1):5407. doi: 10.1038/s41598-017-05514-7.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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.