Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXAAA11)

• DOT Name: B-cell scaffold protein with ankyrin repeats (BANK1)
• Gene Name: BANK1
• Related Disease:
  Small lymphocytic lymphoma
  Cardiovascular disease
  Dermatomyositis
  Diffuse systemic sclerosis
  Inflammatory bowel disease
  Insulinoma
  Lupus
  Multiple sclerosis
  Psoriasis
  Scleroderma
  Systemic sclerosis
  Graft-versus-host disease
  Graves disease
  Hashimoto thyroiditis
  Ankylosing spondylitis
  Autoimmune disease
  Crohn disease
  Sclerosing cholangitis
  Type-1 diabetes
  Ulcerative colitis
• UniProt ID: BANK1_HUMAN
• Pfam ID: PF14545 ; PF18567
• Sequence:
  MLPAAPGKGLGSPDPAPCGPAPPGNTKDIIMIYEEDAEEWALYLTEVFLHVVKREAILLY
  RLENFSFRHLELLNLTSYKCKLLILSNSLLRDLTPKKCQFLEKILHSPKSVVTLLCGVKS
  SDQLYELLNISQSRWEISTEQEPEDYISVIQSIIFKDSEDYFEVNIPTDLRAKHSGEISE
  RKEIEELSEASRNTIPLAVVLPTEIPCENPGEIFIILRDEVIGDTVEVEFTSSNKRIRTR
  PALWNKKVWCMKALEFPAGSVHVNVYCDGIVKATTKIKYYPTAKAKECLFRMADSGESLC
  QNSIEELDGVLTSIFKHEIPYYEFQSLQTEICSQNKYTHFKELPTLLHCAAKFGLKNLAI
  HLLQCSGATWASKMKNMEGSDPAHIAERHGHKELKKIFEDFSIQEIDINNEQENDYEEDI
  ASFSTYIPSTQNPAFHHESRKTYGQSADGAEANEMEGEGKQNGSGMETKHSPLEVGSESS
  EDQYDDLYVFIPGADPENNSQEPLMSSRPPLPPPRPVANAFQLERPHFTLPGTMVEGQME
  RSQNWGHPGVRQETGDEPKGEKEKKEEEKEQEEEEDPYTFAEIDDSEYDMILANLSIKKK
  TGSRSFIINRPPAPTPRPTSIPPKEETTPYIAQVFQQKTARRQSDDDKFCGLPKKQDRAR
  IESPAFSTLRGCLTDGQEELILLQEKVKNGKMSMDEALEKFKHWQMGKSGLEMIQQEKLR
  QLRDCIIGKRPEEENVYNKLTIVHHPGGKETAHNENKFYNVHFSNKLPARPQVEKEFGFC
  CKKDH
• Function: Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores. Promotes Lyn-mediated phosphorylation of IP3 receptors 1 and 2.
• Tissue Specificity: Expressed in B-cell but not T-cell or myeloid cell lines. Highest expression in CD19(+) B-cells, with very low expression in other cell populations.
• KEGG Pathway: B cell receptor sig.ling pathway (hsa04662)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small lymphocytic lymphoma	DIS30POX	Definitive	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Dermatomyositis	DIS50C5O	Strong	Genetic Variation	[3]
Diffuse systemic sclerosis	DISYF5LP	Strong	Genetic Variation	[4]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[5]
Insulinoma	DISIU1JS	Strong	Altered Expression	[6]
Lupus	DISOKJWA	Strong	Genetic Variation	[7]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[8]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[9]
Scleroderma	DISVQ342	Strong	Biomarker	[10]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[11]
Graft-versus-host disease	DIS0QADF	moderate	Genetic Variation	[12]
Graves disease	DISU4KOQ	moderate	Genetic Variation	[13]
Hashimoto thyroiditis	DIS77CDF	moderate	Genetic Variation	[13]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[9]
Autoimmune disease	DISORMTM	Limited	Biomarker	[14]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[15]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[9]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[16]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[9]

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 B-cell scaffold protein with ankyrin repeats (BANK1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of B-cell scaffold protein with ankyrin repeats (BANK1).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[20]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[26]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of B-cell scaffold protein with ankyrin repeats (BANK1).	[27]

References

• [1] Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.Nat Commun. 2017 Feb 6;8:14175. doi: 10.1038/ncomms14175.
• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] Association between the BANK1 rs3733197 polymorphism and polymyositis/dermatomyositis in a Chinese Han population.Clin Rheumatol. 2019 Feb;38(2):431-436. doi: 10.1007/s10067-018-4257-1. Epub 2018 Aug 25.
• [4] BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians.Ann Rheum Dis. 2010 Apr;69(4):700-5. doi: 10.1136/ard.2009.118174. Epub 2009 Oct 8.
• [5] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [6] DcR3 protects islet beta cells from apoptosis through modulating Adcyap1 and Bank1 expression.J Immunol. 2009 Dec 15;183(12):8157-66. doi: 10.4049/jimmunol.0901165.
• [7] Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus.Nat Commun. 2019 May 17;10(1):2201. doi: 10.1038/s41467-019-10242-9.
• [8] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
• [9] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [10] The genetics of scleroderma (systemic sclerosis).Curr Opin Rheumatol. 2010 Mar;22(2):133-8. doi: 10.1097/BOR.0b013e3283367c17.
• [11] Association study of B-cell marker gene polymorphisms in European Caucasian patients with systemic sclerosis.Clin Exp Rheumatol. 2011 Sep-Oct;29(5):839-42. Epub 2011 Oct 31.
• [12] Genetic risk factors for sclerotic graft-versus-host disease.Blood. 2016 Sep 15;128(11):1516-24. doi: 10.1182/blood-2016-05-715342. Epub 2016 Jun 16.
• [13] Genetic variants of BANK1 gene in autoimmune thyroid diseases: a case-control association study.Exp Clin Endocrinol Diabetes. 2013 Oct;121(9):556-60. doi: 10.1055/s-0033-1348220. Epub 2013 Oct 14.
• [14] Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development.PLoS One. 2018 Jul 17;13(7):e0199979. doi: 10.1371/journal.pone.0199979. eCollection 2018.
• [15] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [16] Association of BANK1 and cytokine gene polymorphisms with type 1 diabetes in Tunisia.Gene. 2014 Feb 25;536(2):296-301. doi: 10.1016/j.gene.2013.12.008. Epub 2013 Dec 14.
• [17] 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.
• [18] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] 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.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [23] 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.
• [24] 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.
• [25] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.