Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWQ6GA3)

• DOT Name: BTB/POZ domain-containing protein 9 (BTBD9)
• Gene Name: BTBD9
• Related Disease:
  Chronic renal failure
  End-stage renal disease
  Attention deficit hyperactivity disorder
  Chronic obstructive pulmonary disease
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Hemochromatosis
  Obsessive compulsive disorder
  Schizophrenia
  Tourette syndrome
  Trichohepatoenteric syndrome
  Acute myelogenous leukaemia
  Lung squamous cell carcinoma
• UniProt ID: BTBD9_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF00754
• Sequence:
  MSNSHPLRPFTAVGEIDHVHILSEHIGALLIGEEYGDVTFVVEKKRFPAHRVILAARCQY
  FRALLYGGMRESQPEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLLDFLSLAHKY
  GFPELEDSTSEYLCTILNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLS
  LSKTALLNIVLRDSFAAPEKDIFLALLNWCKHNSKENHAEIMQAVRLPLMSLTELLNVVR
  PSGLLSPDAILDAIKVRSESRDMDLNYRGMLIPEENIATMKYGAQVVKGELKSALLDGDT
  QNYDLDHGFSRHPIDDDCRSGIEIKLGQPSIINHIRILLWDRDSRSYSYFIEVSMDELDW
  VRVIDHSQYLCRSWQKLYFPARVCRYIRIVGTHNTVNKIFHIVAFECMFTNKTFTLEKGL
  IVPMENVATIADCASVIEGVSRSRNALLNGDTKNYDWDSGYTCHQLGSGAIVVQLAQPYM
  IGSIRLLLWDCDDRSYSYYVEVSTNQQQWTMVADRTKVSCKSWQSVTFERQPASFIRIVG
  THNTANEVFHCVHFECPEQQSSQKEENSEESGTGDTSLAGQQLDSHALRAPSGSSLPSSP
  GSNSRSPNRQHQ
• Tissue Specificity: Detected in the brain (at protein level) . Moderately expressed in all specific brain regions examined . Expressed in the dopaminergic neurons of the substantia nigra and A11 neurons . Highly expressed in kidney and moderately expressed in all other adult and fetal tissues .

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
End-stage renal disease	DISXA7GG	Definitive	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[4]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[4]
Hemochromatosis	DISAPY0H	Strong	Genetic Variation	[5]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[6]
Schizophrenia	DISSRV2N	Strong	Biomarker	[7]
Tourette syndrome	DISX9D54	Strong	Genetic Variation	[8]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[9]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[10]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[11]

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 BTB/POZ domain-containing protein 9 (BTBD9).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of BTB/POZ domain-containing protein 9 (BTBD9).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BTB/POZ domain-containing protein 9 (BTBD9).	[20]

References

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• [2] Exploring the genetic link between RLS and ADHD.J Psychiatr Res. 2009 Jul;43(10):941-5. doi: 10.1016/j.jpsychires.2009.01.003. Epub 2009 Feb 14.
• [3] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [4] Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.Oncotarget. 2017 Oct 9;8(58):98623-98634. doi: 10.18632/oncotarget.21697. eCollection 2017 Nov 17.
• [5] Genetic factors influencing hemoglobin levels in 15,567 blood donors: results from the Danish Blood Donor Study.Transfusion. 2019 Jan;59(1):226-231. doi: 10.1111/trf.15075. Epub 2018 Dec 7.
• [6] Association of intronic variants of the BTBD9 gene with Tourette syndrome.Arch Neurol. 2009 Oct;66(10):1267-72. doi: 10.1001/archneurol.2009.213.
• [7] The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia.Hum Psychopharmacol. 2013 Mar;28(2):117-23. doi: 10.1002/hup.2287. Epub 2013 Jan 30.
• [8] The BTBD9 gene polymorphisms in Polish patients with Gilles de la Tourette syndrome.Acta Neurobiol Exp (Wars). 2014;74(2):218-26. doi: 10.55782/ane-2014-1987.
• [9] Neurological disorders: towards a mechanistic understanding of restless legs syndrome.Curr Biol. 2012 Jun 19;22(12):R485-6. doi: 10.1016/j.cub.2012.05.004.
• [10] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [11] Genome-wide association study of familial lung cancer.Carcinogenesis. 2018 Sep 21;39(9):1135-1140. doi: 10.1093/carcin/bgy080.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [19] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [20] 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.