Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF3FR4A)

• DOT Name: Schwannomin-interacting protein 1 (SCHIP1)
• Synonyms: SCHIP-1
• Gene Name: SCHIP1
• Related Disease:
  Familial adenomatous polyposis
  Complex neurodevelopmental disorder
• UniProt ID: SCHI1_HUMAN
• Pfam ID: PF10148
• Sequence:
  MERSGQRVTTWDCDQGKHSDSDYREDGMDLGSDAGSSSSSSRASSQSNSTKVTPCSECKS
  SSSPGGSLDLVSALEDYEEPFPVYQKKVIDEWAPEEDGEEEEEEDERDQRGYRDDRSPAR
  EPGDVSARTRSGGGGGRSATTAMPPPVPNGNLHQHDPQDLRHNGNVVVAGRPSCSRGPRR
  AIQKPQPAGGRRSGRGPAAGGLCLQPPDGGTCVPEEPPVPPMDWEALEKHLAGLQFREQE
  VRNQGQARTNSTSAQKNERESIRQKLALGSFFDDGPGIYTSCSKSGKPSLSSRLQSGMNL
  QICFVNDSGSDKDSDADDSKTETSLDTPLSPMSKQSSSYSDRDTTEEESESLDDMDFLTR
  QKKLQAEAKMALAMAKPMAKMQVEVEKQNRKKSPVADLLPHMPHISECLMKRSLKPTDLR
  DMTIGQLQVIVNDLHSQIESLNEELVQLLLIRDELHTEQDAMLVDIEDLTRHAESQQKHM
  AEKMPAK
• Tissue Specificity: Preferentially expressed in brain, skeletal muscles and heart. Also expressed in detected in pancreas, kidney, liver, lung, and placenta.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[1]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Schwannomin-interacting protein 1 (SCHIP1) affects the response to substance of Mitoxantrone.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Schwannomin-interacting protein 1 (SCHIP1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Schwannomin-interacting protein 1 (SCHIP1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Schwannomin-interacting protein 1 (SCHIP1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Schwannomin-interacting protein 1 (SCHIP1).	[18]

References

• [1] Microarray analysis of pediatric ependymoma identifies a cluster of 112 candidate genes including four transcripts at 22q12.1-q13.3.Neuro Oncol. 2005 Jan;7(1):20-31. doi: 10.1215/S1152851704000596).
• [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] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [11] 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.
• [12] 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.
• [13] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [14] 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.
• [15] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [16] 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.
• [17] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [18] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [19] 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.