Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1IH086)

• DOT Name: bMERB domain-containing protein 1 (BMERB1)
• Gene Name: BMERB1
• Related Disease: Testicular germ cell tumor
• UniProt ID: MERB1_HUMAN
• Pfam ID: PF12130
• Sequence:
  MELKQSLSTHLEAEKPLRRYGAVEETAWKTERLGRNQLDIISMAETTMMPEEIELEMAKI
  QRLREVLVRRESELRFMMDDIQLCKDIMDLKQELQNLVAIPEKEKTKLQKQREDELIQKI
  HKLVQKRDFLVDDAEVERLREQEEDKEMADFLRIKLKPLDKVTKSPASSRAEKKAEPPPS
  KPTVAKTGLALIKDCCGATQCNIM

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of bMERB domain-containing protein 1 (BMERB1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of bMERB domain-containing protein 1 (BMERB1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of bMERB domain-containing protein 1 (BMERB1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of bMERB domain-containing protein 1 (BMERB1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of bMERB domain-containing protein 1 (BMERB1).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of bMERB domain-containing protein 1 (BMERB1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of bMERB domain-containing protein 1 (BMERB1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of bMERB domain-containing protein 1 (BMERB1).	[10]

References

• [1] Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.Nat Genet. 2017 Jul;49(7):1133-1140. doi: 10.1038/ng.3896. Epub 2017 Jun 12.
• [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] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] 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.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [13] 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.
• [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.