Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKKI81C)

• DOT Name: Tetratricopeptide repeat protein 39C (TTC39C)
• Synonyms: TPR repeat protein 39C
• Gene Name: TTC39C
• Related Disease: Non-insulin dependent diabetes
• UniProt ID: TT39C_HUMAN
• Pfam ID: PF10300
• Sequence:
  MAGSEQQRPRRRDDGDSDAAAAAAAPLQDAELALAGINMLLNNGFRESDQLFKQYRNHSP
  LMSFGASFVSFLNAMMTFEEEKMQLACDDLKTTEKLCESEEAGVIETIKNKIKKNVDVRK
  SAPSMVDRLQRQIIIADCQVYLAVLSFVKQELSAYIKGGWILRKAWKIYNKCYLDINALQ
  ELYQKKLTEESLTSDAANDNHIVAEGVSEESLNRLKGAVSFGYGLFHLCISMVPPNLLKI
  INLLGFPGDRLQGLSSLMYASESKDMKAPLATLALLWYHTVVRPFFALDGSDNKAGLDEA
  KEILLKKEAAYPNSSLFMFFKGRIQRLECQINSALTSFHTALELAVDQREIQHVCLYEIG
  WCSMIELNFKDAFDSFERLKNESRWSQCYYAYLTAVCQGATGDVDGAQIVFKEVQKLFKR
  KNNQIEQFSVKKAERFRKQTPTKALCVLASIEVLYLWKALPNCSFPNLQRMSQACHEVDD
  SSVVGLKYLLLGAIHKCLGNSEDAVQYFQRAVKDELCRQNNLYVQPYACYELGCLLLDKP
  ETVGRGRALLLQAKEDFSGYDFENRLHVRIHAALASLRELVPQ

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Tetratricopeptide repeat protein 39C (TTC39C).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tetratricopeptide repeat protein 39C (TTC39C).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tetratricopeptide repeat protein 39C (TTC39C).	[18]

References

• [1] A genome-wide association study implicates that the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity.Ophthalmic Genet. 2019 Jun;40(3):252-258. doi: 10.1080/13816810.2019.1633549. Epub 2019 Jul 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] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] 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.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] 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.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.