Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0UZ3EP)

• DOT Name: GATA zinc finger domain-containing protein 1 (GATAD1)
• Synonyms: Ocular development-associated gene protein
• Gene Name: GATAD1
• Related Disease:
  Advanced cancer
  Dilated cardiomyopathy 1A
  Familial dilated cardiomyopathy
  Glioma
  Neoplasm
  Choriocarcinoma
  Obsolete familial isolated dilated cardiomyopathy
  Carcinoma of liver and intrahepatic biliary tract
  Dilated cardiomyopathy
  Dilated cardiomyopathy 2B
  Hepatocellular carcinoma
  Liver cancer
• UniProt ID: GATD1_HUMAN
• Sequence:
  MPLGLKPTCSVCKTTSSSMWKKGAQGEILCHHCTGRGGAGSGGAGSGAAGGTGGSGGGGF
  GAATFASTSATPPQSNGGGGGKQSKQEIHRRSARLRNTKYKSAPAAEKKVSTKGKGRRHI
  FKLKNPIKAPESVSTIITAESIFYKGVYYQIGDVVSVIDEQDGKPYYAQIRGFIQDQYCE
  KSAALTWLIPTLSSPRDQFDPASYIIGPEEDLPRKMEYLEFVCHAPSEYFKSRSSPFPTV
  PTRPEKGYIWTHVGPTPAITIKESVANHL
• Function: Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).
• Tissue Specificity: Ubiquitously expressed among various tissue types. Expressed in left ventricular myocytes.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[2]
Familial dilated cardiomyopathy	DISBHDU9	Strong	GermlineCausalMutation	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[3]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[4]
Dilated cardiomyopathy	DISX608J	Limited	Autosomal recessive	[5]
Dilated cardiomyopathy 2B	DIST1JCO	Limited	Autosomal recessive	[6]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[4]
Liver cancer	DISDE4BI	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[18]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of GATA zinc finger domain-containing protein 1 (GATAD1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of GATA zinc finger domain-containing protein 1 (GATAD1).	[14]

References

• [1] GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription.Cancer Med. 2019 Sep;8(11):5242-5253. doi: 10.1002/cam4.2405. Epub 2019 Jul 8.
• [2] Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy. Circ Cardiovasc Genet. 2011 Dec;4(6):585-94. doi: 10.1161/CIRCGENETICS.111.961052. Epub 2011 Sep 30.
• [3] Decreased expression and DNA methylation levels of GATAD1 in preeclamptic placentas.Cell Signal. 2014 May;26(5):959-67. doi: 10.1016/j.cellsig.2014.01.013. Epub 2014 Jan 22.
• [4] Increased expression of GATA zinc finger domain containing 1 through gene amplification promotes liver cancer by directly inducing phosphatase of regenerating liver 3.Hepatology. 2018 Jun;67(6):2302-2319. doi: 10.1002/hep.29750. Epub 2018 Mar 23.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [16] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [19] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.