Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUE51B3)

• DOT Name: Tetratricopeptide repeat protein 7B (TTC7B)
• Synonyms: TPR repeat protein 7B; Tetratricopeptide repeat protein 7-like-1; TPR repeat protein 7-like-1
• Gene Name: TTC7B
• Related Disease:
  Cutaneous melanoma
  Cardiovascular disease
  Stroke
• UniProt ID: TTC7B_HUMAN
• PDB ID: 5DSE; 6BQ1
• Pfam ID: PF12895 ; PF13424 ; PF13181 ; PF19440
• Sequence:
  MATKKAGSRLETEIERCRSECQWERIPELVKQLSAKLIANDDMAELLLGESKLEQYLKEH
  PLRQGASPRGPKPQLTEVRKHLTAALDRGNLKSEFLQESNLIMAKLNYVEGDYKEALNIY
  ARVGLDDLPLTAVPPYRLRVIAEAYATKGLCLEKLPISSSTSNLHVDREQDVITCYEKAG
  DIALLYLQEIERVILSNIQNRSPKPGPAPHDQELGFFLETGLQRAHVLYFKNGNLTRGVG
  RFRELLRAVETRTTQNLRMTIARQLAEILLRGMCEQSYWNPLEDPPCQSPLDDPLRKGAN
  TKTYTLTRRARVYSGENIFCPQENTEEALLLLLISESMANRDAVLSRIPEHKSDRLISLQ
  SASVVYDLLTIALGRRGQYEMLSECLERAMKFAFEEFHLWYQFALSLMAAGKSARAVKVL
  KECIRLKPDDATIPLLAAKLCMGSLHWLEEAEKFAKTVVDVGEKTSEFKAKGYLALGLTY
  SLQATDASLRGMQEVLQRKALLAFQRAHSLSPTDHQAAFYLALQLAISRQIPEALGYVRQ
  ALQLQGDDANSLHLLALLLSAQKHYHDALNIIDMALSEYPENFILLFSKVKLQSLCRGPD
  EALLTCKHMLQIWKSCYNLTNPSDSGRGSSLLDRTIADRRQLNTITLPDFSDPETGSVHA
  TSVAASRVEQALSEVASSLQSSAPKQGPLHPWMTLAQIWLHAAEVYIGIGKPAEATACTQ
  EAANLFPMSHNVLYMRGQIAELRGSMDEARRWYEEALAISPTHVKSMQRLALILHQLGRY
  SLAEKILRDAVQVNSTAHEVWNGLGEVLQAQGNDAAATECFLTALELEASSPAVPFTIIP
  RVL
• Function: Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Stroke	DISX6UHX	Strong	Biomarker	[2]

12 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 Tetratricopeptide repeat protein 7B (TTC7B).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tetratricopeptide repeat protein 7B (TTC7B).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cotinine	DMCEZ1B	Approved	Cotinine affects the methylation of Tetratricopeptide repeat protein 7B (TTC7B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tetratricopeptide repeat protein 7B (TTC7B).	[15]

References

• [1] Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.Nat Commun. 2018 Nov 14;9(1):4774. doi: 10.1038/s41467-018-06649-5.
• [2] TTC7B emerges as a novel risk factor for ischemic stroke through the convergence of several genome-wide approaches.J Cereb Blood Flow Metab. 2012 Jun;32(6):1061-72. doi: 10.1038/jcbfm.2012.24. Epub 2012 Mar 28.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] 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.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2012 Oct;120(10):1425-31. doi: 10.1289/ehp.1205412. Epub 2012 Jul 31.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] 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.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.