Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNTKWS2)

• DOT Name: Protein turtle homolog A (IGSF9)
• Synonyms: Immunoglobulin superfamily member 9A; IgSF9A
• Gene Name: IGSF9
• Related Disease:
  Advanced cancer
  Endometrial cancer
  Endometrial carcinoma
  Insulinoma
  Pancreatic ductal carcinoma
  Pancreatitis
• UniProt ID: TUTLA_HUMAN
• PDB ID: 1V5J
• Pfam ID: PF00041 ; PF13927
• Sequence:
  MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRF
  GFLLPIFIQFGLYSPRIDPDYVGRVRLQKGASLQIEGLRVEDQGWYECRVFFLDQHIPED
  DFANGSWVHLTVNSPPQFQETPPAVLEVQELEPVTLRCVARGSPLPHVTWKLRGKDLGQG
  QGQVQVQNGTLRIRRVERGSSGVYTCQASSTEGSATHATQLLVLGPPVIVVPPKNSTVNA
  SQDVSLACHAEAYPANLTYSWFQDNINVFHISRLQPRVRILVDGSLRLLATQPDDAGCYT
  CVPSNGLLHPPSASAYLTVLYPAQVTAMPPETPLPIGMPGVIRCPVRANPPLLFVSWTKD
  GKALQLDKFPGWSQGTEGSLIIALGNEDALGEYSCTPYNSLGTAGPSPVTRVLLKAPPAF
  IERPKEEYFQEVGRELLIPCSAQGDPPPVVSWTKVGRGLQGQAQVDSNSSLILRPLTKEA
  HGHWECSASNAVARVATSTNVYVLGTSPHVVTNVSVVALPKGANVSWEPGFDGGYLQRFS
  VWYTPLAKRPDRMHHDWVSLAVPVGAAHLLVPGLQPHTQYQFSVLAQNKLGSGPFSEIVL
  SAPEGLPTTPAAPGLPPTEIPPPLSPPRGLVAVRTPRGVLLHWDPPELVPKRLDGYVLEG
  RQGSQGWEVLDPAVAGTETELLVPGLIKDVLYEFRLVAFAGSFVSDPSNTANVSTSGLEV
  YPSRTQLPGLLPQPVLAGVVGGVCFLGVAVLVSILAGCLLNRRRAARRRRKRLRQDPPLI
  FSPTGKSAAPSALGSGSPDSVAKLKLQGSPVPSLRQSLLWGDPAGTPSPHPDPPSSRGPL
  PLEPICRGPDGRFVMGPTVAAPQERSGREQAEPRTPAQRLARSFDCSSSSPSGAPQPLCI
  EDISPVAPPPAAPPSPLPGPGPLLQYLSLPFFREMNVDGDWPPLEEPSPAAPPDYMDTRR
  CPTSSFLRSPETPPVSPRESLPGAVVGAGATAEPPYTALADWTLRERLLPGLLPAAPRGS
  LTSQSSGRGSASFLRPPSTAPSAGGSYLSPAPGDTSSWASGPERWPRREHVVTVSKRRNT
  SVDENYEWDSEFPGDMELLETLHLGLASSRLRPEAEPELGVKTPEEGCLLNTAHVTGPEA
  RCAALREEFLAFRRRRDATRARLPAYRQPVPHPEQATLL
• Function: Functions in dendrite outgrowth and synapse maturation.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[1]
Insulinoma	DISIU1JS	Strong	Altered Expression	[2]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[2]
Pancreatitis	DIS0IJEF	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein turtle homolog A (IGSF9).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein turtle homolog A (IGSF9).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein turtle homolog A (IGSF9).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein turtle homolog A (IGSF9).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein turtle homolog A (IGSF9).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein turtle homolog A (IGSF9).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein turtle homolog A (IGSF9).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein turtle homolog A (IGSF9).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein turtle homolog A (IGSF9).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein turtle homolog A (IGSF9).	[5]

References

• [1] RNA-seq Reveals the Overexpression of IGSF9 in Endometrial Cancer.J Oncol. 2018 Feb 14;2018:2439527. doi: 10.1155/2018/2439527. eCollection 2018.
• [2] Evaluation of neurotensin receptor 1 as a potential imaging target in pancreatic ductal adenocarcinoma.Amino Acids. 2017 Aug;49(8):1325-1335. doi: 10.1007/s00726-017-2430-5. Epub 2017 May 23.
• [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] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [5] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] 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.