Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5GE8IO)

• DOT Name: Testis-expressed basic protein 1 (TSBP1)
• Synonyms: Uncharacterized protein C6orf10
• Gene Name: TSBP1
• Related Disease:
  Non-insulin dependent diabetes
  Alopecia areata
  Atopic dermatitis
  Frontotemporal dementia
  Graves disease
  Hypothyroidism
  Juvenile idiopathic arthritis
  Lung adenocarcinoma
  Membranous glomerulonephritis
  Multiple sclerosis
  Myasthenia gravis
  Narcolepsy
  Polymyalgia rheumatica
  Primary biliary cholangitis
  Sarcoidosis
  Schizophrenia
  Type-1 diabetes
  Vitiligo
  Asthma
  Small lymphocytic lymphoma
  Amyotrophic lateral sclerosis
  Bipolar disorder
  Lung cancer
  Pick disease
  Systemic lupus erythematosus
• UniProt ID: TSBP1_HUMAN
• Sequence:
  MTVLEITLAVILTLLGLAILAILLTRWARCKQSEMYISRYSSEQSARLLDYEDGRGSRHA
  YSTQSDTSYDNRERSKRDYTPSTNSLVSMASKFSLGQTELILLLMCFILALSRSSIGSIK
  CLQTTEEPPSRTAGAMMQFTAPIPGATGPIKLSQKTIVQTPGPIVQYPGSNAGPPSAPRG
  PPMAPIIISQRTARIPQVHTMDSSGKITLTPVVILTGYMDEELAKKSCSKIQILKCGGTA
  RSQNSREENKEALKNDIIFTNSVESLKSAHIKEPEREGKGTDLEKDKIGMEVKVDSDAGI
  PKRQETQLKISEMSIPQGQGAQIKKSVSDVPRGQESQVKKSESGVPKGQEAQVTKSGLVV
  LKGQEAQVEKSEMGVPRRQESQVKKSQSGVSKGQEAQVKKRESVVLKGQEAQVEKSELKV
  PKGQEGQVEKTEADVPKEQEVQEKKSEAGVLKGPESQVKNTEVSVPETLESQVKKSESGV
  LKGQEAQEKKESFEDKGNNDKEKERDAEKDPNKKEKGDKNTKGDKGKDKVKGKRESEING
  EKSKGSKRAKANTGRKYNKKVEE

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Alopecia areata	DIS0XXBJ	Strong	Genetic Variation	[2]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[3]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[4]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[5]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[6]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[7]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[8]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[9]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[10]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[11]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[12]
Polymyalgia rheumatica	DIS5F36E	Strong	Genetic Variation	[6]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[13]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[14]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[15]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[16]
Vitiligo	DISR05SL	Strong	Genetic Variation	[17]
Asthma	DISW9QNS	moderate	Genetic Variation	[18]
Small lymphocytic lymphoma	DIS30POX	Disputed	Genetic Variation	[19]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[20]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[21]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[22]
Pick disease	DISP6X50	Limited	Biomarker	[20]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Testis-expressed basic protein 1 (TSBP1) increases the Liver injury ADR of Aspirin.	[27]

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 Testis-expressed basic protein 1 (TSBP1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Testis-expressed basic protein 1 (TSBP1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Testis-expressed basic protein 1 (TSBP1).	[25]

References

• [1] Phenome-Wide Association Study to Explore Relationships between Immune System Related Genetic Loci and Complex Traits and Diseases.PLoS One. 2016 Aug 10;11(8):e0160573. doi: 10.1371/journal.pone.0160573. eCollection 2016.
• [2] Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata.Eur J Hum Genet. 2012 Mar;20(3):326-32. doi: 10.1038/ejhg.2011.185. Epub 2011 Oct 26.
• [3] Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.Nat Genet. 2012 Nov;44(11):1222-6. doi: 10.1038/ng.2438. Epub 2012 Oct 7.
• [4] An update on genetic frontotemporal dementia.J Neurol. 2019 Aug;266(8):2075-2086. doi: 10.1007/s00415-019-09363-4. Epub 2019 May 22.
• [5] Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.J Hum Genet. 2011 Nov;56(11):772-8. doi: 10.1038/jhg.2011.99. Epub 2011 Sep 8.
• [6] Identifying genetically driven clinical phenotypes using linear mixed models.Nat Commun. 2016 Apr 25;7:11433. doi: 10.1038/ncomms11433.
• [7] Association of the TRAF1-C5 locus on chromosome 9 with juvenile idiopathic arthritis.Arthritis Rheum. 2008 Jul;58(7):2206-7. doi: 10.1002/art.23603.
• [8] A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.Am J Hum Genet. 2009 Nov;85(5):679-91. doi: 10.1016/j.ajhg.2009.09.012. Epub 2009 Oct 15.
• [9] Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
• [10] A genome-wide association study in progressive multiple sclerosis.Mult Scler. 2012 Oct;18(10):1384-94. doi: 10.1177/1352458512439118. Epub 2012 Mar 28.
• [11] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [12] Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy.Nat Genet. 2010 Sep;42(9):786-9. doi: 10.1038/ng.647. Epub 2010 Aug 15.
• [13] Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.N Engl J Med. 2009 Jun 11;360(24):2544-55. doi: 10.1056/NEJMoa0810440. Epub 2009 May 20.
• [14] High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.Am J Respir Crit Care Med. 2016 May 1;193(9):1008-22. doi: 10.1164/rccm.201507-1372OC.
• [15] Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
• [16] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [17] Genome-wide analysis identifies a quantitative trait locus in the MHC class II region associated with generalized vitiligo age of onset.J Invest Dermatol. 2011 Jun;131(6):1308-12. doi: 10.1038/jid.2011.12. Epub 2011 Feb 17.
• [18] Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.Nat Genet. 2011 Jul 31;43(9):893-6. doi: 10.1038/ng.887.
• [19] A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.
• [20] A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.Brain. 2018 Oct 1;141(10):2895-2907. doi: 10.1093/brain/awy238.
• [21] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [22] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [23] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [24] 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.
• [25] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [26] 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.
• [27] A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet. 2010 Aug;42(8):711-4. doi: 10.1038/ng.632. Epub 2010 Jul 18.