Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL29A51)

• DOT Name: Tetratricopeptide repeat protein 9A (TTC9)
• Synonyms: TPR repeat protein 9A
• Gene Name: TTC9
• Related Disease: Opioid dependence
• UniProt ID: TTC9A_HUMAN
• Pfam ID: PF07719
• Sequence:
  MERKGSAAGAKGNPSPPAAGEGQRPPPPLCVPGGGGGAPARGQVGAAAEPAELIRRAHEF
  KSQGAQCYKDKKFREAIGKYHRALLELKGLLPPPGERERDSRPASPAGALKPGRLSEEQS
  KTVEAIEIDCYNSLAACLLQAELVNYERVKEYCLKVLKKEGENFKALYRSGVAFYHLGDY
  DKALYYLKEARTQQPTDTNVIRYIQLTEMKLSRCSQREKEAM

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Opioid dependence	DIS6WEHK	Strong	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 increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[9]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Tetratricopeptide repeat protein 9A (TTC9).	[10]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Tetratricopeptide repeat protein 9A (TTC9).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tetratricopeptide repeat protein 9A (TTC9).	[12]

References

• [1] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.