Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLPN3D0)

• DOT Name: Mirror-image polydactyly gene 1 protein (MIPOL1)
• Gene Name: MIPOL1
• Related Disease:
  Polydactyly
  Neoplasm
  Laurin-Sandrow syndrome
• UniProt ID: MIPO1_HUMAN
• Sequence:
  MENWSKDITHSYLEQETTGINKSTQPDEQLTMNSEKSMHRKSTELVNEITCENTEWPGQR
  STNFQIISSYPDDESVYCTTEKYNVMEHRHNDMHYECMTPCQVTSDSDKEKTIAFLLKEL
  DILRTSNKKLQQKLAKEDKEQRKLKFKLELQEKETEAKIAEKTAALVEEVYFAQKERDEA
  VMSRLQLAIEERDEAIARAKHMEMSLKVLENINPEENDMTLQELLNRINNADTGIAIQKN
  GAIIVDRIYKTKECKMRITAEEMSALIEERDAALSKCKRLEQELHHVKEQNQTSANNMRH
  LTAENNQERALKAKLLSMQQARETAVQQYKKLEEEIQTLRVYYSLHKSLSQEENLKDQFN
  YTLSTYEEALKNRENIVSITQQQNEELATQLQQALTERANMELQLQHAREASQVANEKVQ
  KLERLVDVLRKKVGTGTMRTVI
• Tissue Specificity: Expressed very weakly in heart, liver, skeletal muscle, kidney, pancreas and fetal kidney. Not detected in brain, placenta and lung.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polydactyly	DIS25BMZ	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]
Laurin-Sandrow syndrome	DISOYBC3	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Mirror-image polydactyly gene 1 protein (MIPOL1) affects the binding of PEITC.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[8]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mirror-image polydactyly gene 1 protein (MIPOL1).	[13]

References

• [1] Exome sequencing revealed a splice site variant in the IQCE gene underlying post-axial polydactyly type A restricted to lower limb. Eur J Hum Genet. 2017 Aug;25(8):960-965. doi: 10.1038/ejhg.2017.83. Epub 2017 May 10.
• [2] Functional characterization of a candidate tumor suppressor gene, Mirror Image Polydactyly 1, in nasopharyngeal carcinoma.Int J Cancer. 2020 May 15;146(10):2891-2900. doi: 10.1002/ijc.32732. Epub 2019 Nov 1.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.