Details of Drug Off-Target (DOT)

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

• DOT Name: Small integral membrane protein 8 (SMIM8)
• Gene Name: SMIM8
• Related Disease: Bipolar disorder
• UniProt ID: SMIM8_HUMAN
• Pfam ID: PF14937
• Sequence:
  MSSAPEPPTFKKEPPKEKEFQSPGLRGVRTTTLFRAVNPELFIKPNKPVMAFGLVTLSLC
  VAYIGYLHAIQENKKDLYEAIDSEGHSYMRRKTSKWD

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[1]

12 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 Small integral membrane protein 8 (SMIM8).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small integral membrane protein 8 (SMIM8).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small integral membrane protein 8 (SMIM8).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Small integral membrane protein 8 (SMIM8).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small integral membrane protein 8 (SMIM8).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Small integral membrane protein 8 (SMIM8).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small integral membrane protein 8 (SMIM8).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Small integral membrane protein 8 (SMIM8).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Small integral membrane protein 8 (SMIM8).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Small integral membrane protein 8 (SMIM8).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small integral membrane protein 8 (SMIM8).	[13]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Small integral membrane protein 8 (SMIM8).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Small integral membrane protein 8 (SMIM8).	[7]

References

• [1] Genetics of long-term treatment outcome in bipolar disorder.Prog Neuropsychopharmacol Biol Psychiatry. 2016 Feb 4;65:17-24. doi: 10.1016/j.pnpbp.2015.08.008. Epub 2015 Aug 20.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.