Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT05YQ1E)

• DOT Name: Transmembrane protein 18 (TMEM18)
• Gene Name: TMEM18
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
  Acute myelogenous leukaemia
  Arteriosclerosis
  Atherosclerosis
  Polycystic ovarian syndrome
  Type-1/2 diabetes
  Non-insulin dependent diabetes
  Asthma
• UniProt ID: TMM18_HUMAN
• Pfam ID: PF14770
• Sequence:
  MPSAFSVSSFPVSIPAVLTQTDWTEPWLMGLATFHALCVLLTCLSSRSYRLQIGHFLCLV
  ILVYCAEYINEAAAMNWRLFSKYQYFDSRGMFISIVFSAPLLVNAMIIVVMWVWKTLNVM
  TDLKNAQERRKEKKRRRKED
• Function: Transcription repressor. Sequence-specific ssDNA and dsDNA binding protein, with preference for GCT end CTG repeats. Cell migration modulator which enhances the glioma-specific migration ability of neural stem cells (NSC) and neural precursor cells (NPC).

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[5]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[6]
Asthma	DISW9QNS	Limited	Genetic Variation	[7]

10 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 Transmembrane protein 18 (TMEM18).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 18 (TMEM18).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 18 (TMEM18).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transmembrane protein 18 (TMEM18).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane protein 18 (TMEM18).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Transmembrane protein 18 (TMEM18).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transmembrane protein 18 (TMEM18).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transmembrane protein 18 (TMEM18).	[15]
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of Transmembrane protein 18 (TMEM18).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transmembrane protein 18 (TMEM18).	[17]

References

• [1] Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells.Cancer Res. 2008 Jun 15;68(12):4614-22. doi: 10.1158/0008-5472.CAN-07-5291.
• [2] TMEM18: A Novel Prognostic Marker in Acute Myeloid Leukemia.Acta Haematol. 2018;140(2):71-76. doi: 10.1159/000492742. Epub 2018 Sep 10.
• [3] Sequence variation in TMEM18 in association with body mass index: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.Circ Cardiovasc Genet. 2014 Jun;7(3):344-9. doi: 10.1161/CIRCGENETICS.13.000067.
• [4] BMI-associated alleles do not constitute risk alleles for polycystic ovary syndrome independently of BMI: a case-control study.PLoS One. 2014 Jan 31;9(1):e87335. doi: 10.1371/journal.pone.0087335. eCollection 2014.
• [5] Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes.Gene. 2013 Sep 25;527(2):462-8. doi: 10.1016/j.gene.2013.06.079. Epub 2013 Jul 13.
• [6] Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes.Obes Facts. 2019;12(3):328-343. doi: 10.1159/000500490. Epub 2019 Jun 5.
• [7] Obese individuals experience wheezing without asthma but not asthma without wheezing: a Mendelian randomisation study of 85,437 adults from the Copenhagen General Population Study.Thorax. 2016 Mar;71(3):247-54. doi: 10.1136/thoraxjnl-2015-207379. Epub 2015 Oct 26.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] 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.
• [11] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [12] 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.
• [13] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] 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.
• [16] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.