Details of Drug Off-Target (DOT)

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

• DOT Name: Mid1-interacting protein 1 (MID1IP1)
• Synonyms: Gastrulation-specific G12-like protein; Mid1-interacting G12-like protein; Protein STRAIT11499; Spot 14-related protein; S14R; Spot 14-R
• Gene Name: MID1IP1
• Related Disease:
  Androgen insensitivity syndrome
  Fatty liver disease
  Hyperlipidemia
  X-linked Opitz G/BBB syndrome
• UniProt ID: M1IP1_HUMAN
• Pfam ID: PF07084
• Sequence:
  MMQICDTYNQKHSLFNAMNRFIGAVNNMDQTVMVPSLLRDVPLADPGLDNDVGVEVGGSG
  GCLEERTPPVPDSGSANGSFFAPSRDMYSHYVLLKSIRNDIEWGVLHQPPPPAGSEEGSA
  WKSKDILVDLGHLEGADAGEEDLEQQFHYHLRGLHTVLSKLTRKANILTNRYKQEIGFGN
  WGH
• Function: Plays a role in the regulation of lipogenesis in liver. Up-regulates ACACA enzyme activity. Required for efficient lipid biosynthesis, including triacylglycerol, diacylglycerol and phospholipid. Involved in stabilization of microtubules.
• Reactome Pathway: Carnitine metabolism (R-HSA-200425)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[1]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[2]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[2]
X-linked Opitz G/BBB syndrome	DISQ14EC	Strong	Biomarker	[3]

12 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 Mid1-interacting protein 1 (MID1IP1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mid1-interacting protein 1 (MID1IP1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Mid1-interacting protein 1 (MID1IP1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mid1-interacting protein 1 (MID1IP1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mid1-interacting protein 1 (MID1IP1).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Mid1-interacting protein 1 (MID1IP1).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Mid1-interacting protein 1 (MID1IP1).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Mid1-interacting protein 1 (MID1IP1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mid1-interacting protein 1 (MID1IP1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mid1-interacting protein 1 (MID1IP1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mid1-interacting protein 1 (MID1IP1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mid1-interacting protein 1 (MID1IP1).	[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 Mid1-interacting protein 1 (MID1IP1).	[8]

References

• [1] Spot14/Spot14R expression may be involved in MSC adipogenic differentiation in patients with adolescent idiopathic scoliosis.Mol Med Rep. 2016 Jun;13(6):4636-42. doi: 10.3892/mmr.2016.5109. Epub 2016 Apr 12.
• [2] Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC.Int J Mol Sci. 2019 Jan 29;20(3):582. doi: 10.3390/ijms20030582.
• [3] Mig12, a novel Opitz syndrome gene product partner, is expressed in the embryonic ventral midline and co-operates with Mid1 to bundle and stabilize microtubules.BMC Cell Biol. 2004 Feb 29;5:9. doi: 10.1186/1471-2121-5-9.
• [4] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [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] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [11] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] 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.