Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT09YHAQ)

• DOT Name: Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS)
• Synonyms: ADAMS proteinase-related protein; Solute carrier family 7 member 6 opposite strand transcript
• Gene Name: SLC7A6OS
• Related Disease:
  Schizophrenia
  Epilepsy
  Epilepsy, progressive myoclonic, 12
• UniProt ID: S7A6O_HUMAN
• Pfam ID: PF08574
• Sequence:
  MEAARTAVLRVKRKRSAEPAEALVLACKRLRSDAVESAAQKTSEGLERAAENNVFHLVAT
  VCSQEEPVQPLLREVLRPSRDSQQRVRRNLRASAREVRQEGRYRVLSSRRSLGTTSSGQE
  SEYTPGNPEAAGNSGFQLLDLVHEEGEPEAASAGSCKTSDPDVILCNSVELIRERLTVSE
  DGPGVRRQEEQKHDDYVYDIYYLETATPGWIENILSVQPYSQEWELVNDDQEPEDIYDDE
  DDENSENNWRNEYPEEESSDGDEDSRGSADYNSLSEEERGSSRQRMWSKYPLDVQKEFGY
  DSPHDLDSD
• Function: Directs RNA polymerase II nuclear import.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Epilepsy	DISBB28L	Limited	Autosomal recessive	[2]
Epilepsy, progressive myoclonic, 12	DISVT955	Limited	Autosomal recessive	[3]

7 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 Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS).	[11]

References

• [1] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Progressive Myoclonus Epilepsy Caused by a Homozygous Splicing Variant of SLC7A6OS. Ann Neurol. 2021 Feb;89(2):402-407. doi: 10.1002/ana.25941. Epub 2020 Nov 5.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.