Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZA6I9L)

• DOT Name: Transmembrane protein 139 (TMEM139)
• Gene Name: TMEM139
• Related Disease: Thyroid gland papillary carcinoma
• UniProt ID: TM139_HUMAN
• Sequence:
  MVPMHLLGRLEKPLLLLCCASFLLGLALLGIKTDITPVAYFFLTLGGFFLFAYLLVRFLE
  WGLRSQLQSMQTESPGPSGNARDNEAFEVPVYEEAVVGLESQCRPQELDQPPPYSTVVIP
  PAPEEEQPSHPEGSRRAKLEQRRMASEGSMAQEGSPGRAPINLRLRGPRAVSTAPDLQSL
  AAVPTLEPLTPPPAYDVCFGHPDDDSVFYEDNWAPP
• Function: May be involved in cellular trafficking of proteins such as SLC4A1.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[1]

13 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 139 (TMEM139).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 139 (TMEM139).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 139 (TMEM139).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 139 (TMEM139).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 139 (TMEM139).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 139 (TMEM139).	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Transmembrane protein 139 (TMEM139).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane protein 139 (TMEM139).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transmembrane protein 139 (TMEM139).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protein 139 (TMEM139).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 139 (TMEM139).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transmembrane protein 139 (TMEM139).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transmembrane protein 139 (TMEM139).	[13]

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 increases the phosphorylation of Transmembrane protein 139 (TMEM139).	[12]

References

• [1] A novel RNA sequencing-based risk score model to predict papillary thyroid carcinoma recurrence.Clin Exp Metastasis. 2020 Apr;37(2):257-267. doi: 10.1007/s10585-019-10011-4. Epub 2019 Dec 2.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] 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.
• [8] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [9] 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.
• [10] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [11] 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.
• [12] 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.
• [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.