Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBOXM33)

• DOT Name: Protein DGCR6 (DGCR6)
• Synonyms: DiGeorge syndrome critical region 6
• Gene Name: DGCR6
• Related Disease:
  DiGeorge syndrome
  Autism
  Schizophrenia
  Shprintzen-Goldberg syndrome
  Velocardiofacial syndrome
  Anxiety disorder
  Autism spectrum disorder
• UniProt ID: DGCR6_HUMAN
• Pfam ID: PF07324
• Sequence:
  MERYAGALEEVADGARQQERHYQLLSALQSLVKELPSSFQQRLSYTTLSDLALALLDGTV
  FEIVQGLLEIQHLTEKSLYNQRLRLQNEHRVLRQALRQKHQEAQQACRPHNLPVLQAAQQ
  RELEAVEHRIREEQRAMDQKIVLELDRKVADQQSTLEKAGVAGFYVTTNPQELMLQMNLL
  ELIRKLQQRGCWAGKAALGLGGPWQLPAAQCDQKGSPVPP
• Function: May play a role in neural crest cell migration into the third and fourth pharyngeal pouches.
• Tissue Specificity: Found in all tissues examined with highest expression in liver, heart and skeletal muscle. Lower levels in pancreas and placenta. Weak expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
DiGeorge syndrome	DIST1RKO	Definitive	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Biomarker	[1]
Velocardiofacial syndrome	DISOSBTY	moderate	Biomarker	[4]
Anxiety disorder	DISBI2BT	Limited	Altered Expression	[5]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Protein DGCR6 (DGCR6) affects the response to substance of Methotrexate.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein DGCR6 (DGCR6).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein DGCR6 (DGCR6).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein DGCR6 (DGCR6).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein DGCR6 (DGCR6).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein DGCR6 (DGCR6).	[12]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Protein DGCR6 (DGCR6).	[13]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Protein DGCR6 (DGCR6).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein DGCR6 (DGCR6).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Protein DGCR6 (DGCR6).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein DGCR6 (DGCR6).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein DGCR6 (DGCR6).	[14]

References

• [1] GABA(B) receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome.Biochem Biophys Res Commun. 2010 Mar 5;393(2):185-9. doi: 10.1016/j.bbrc.2009.12.120. Epub 2009 Dec 28.
• [2] Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.Arch Gen Psychiatry. 2009 Sep;66(9):947-56. doi: 10.1001/archgenpsychiatry.2009.80.
• [3] Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population.Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):13-5. doi: 10.1002/ajmg.b.30049.
• [4] Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes.Hum Genet. 2005 Jun;117(1):70-80. doi: 10.1007/s00439-005-1267-2. Epub 2005 Apr 9.
• [5] Dysregulation of DGCR6 and DGCR6L: psychopathological outcomes in chromosome 22q11.2 deletion syndrome.Transl Psychiatry. 2012 Apr 24;2(4):e105. doi: 10.1038/tp.2012.31.
• [6] The 22q11 PRODH/DGCR6 deletion is frequent in hyperprolinemic subjects but is not a strong risk factor for ASD.Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):377-82. doi: 10.1002/ajmg.b.32416. Epub 2016 Jan 14.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [14] 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.
• [15] 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.
• [16] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.