Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT26DGM9)

• DOT Name: Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B)
• Synonyms: Amyloid-beta protein intracellular domain-associated protein 1; AIDA-1; E2A-PBX1-associated protein; EB-1
• Gene Name: ANKS1B
• Related Disease:
  Nephropathy
  Alcohol dependence
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autism
  Cardiac failure
  Familial adenomatous polyposis
  Heroin dependence
  Leukemia
  Neoplasm
  Neurodevelopmental disorder
  Stroke
  Ulcerative colitis
  Wilson disease
  Alcohol-induced disorders
  Alcohol-related disorders
  Complex neurodevelopmental disorder
  Squamous cell carcinoma
  Bipolar disorder
  Schizophrenia
• UniProt ID: ANS1B_HUMAN
• PDB ID: 2EAM; 2KE7; 2KIV; 2M38
• Pfam ID: PF12796 ; PF00640 ; PF00536
• Sequence:
  MGKDQELLEAARTGNVALVEKLLSGRKGGILGGGSGPLPLSNLLSIWRGPNVNCTDSSGY
  TALHHAALNGHKDIVLKLLQYEASTNVADNKGYFPIHLAAWKGDVEIVKILIHHGPSHSR
  VNEQNNENETALHCAAQYGHSEVVAVLLEELTDPTIRNSKLETPLDLAALYGRLRVVKMI
  ISAHPNLMSCNTRKHTPLHLAARNGHKAVVQVLLEAGMDVSCQTEKGSALHEAALFGKVD
  VVRVLLETGIDANIKDSLGRTVLDILKEHPSQKSLQIATLLQEYLEGVGRSTVLEEPVQE
  DATQETHISSPVESPSQKTKSETVTGELSKLLDEIKLCQEKDYSFEDLCHTISDHYLDNL
  SKISEEELGKNGSQSVRTSSTINLSPGEVEEEDDDENTCGPSGLWEALTPCNGCRNLGFP
  MLAQESYPKKRNYTMEIVPSASLDTFPSENENFLCDLMDTAVTKKPCSLEIARAPSPRTD
  NASEVAVTTPGTSNHRNSSTGPTPDCSPPSPDTALKNIVKVIRPQPKQRTSIVSSLDFHR
  MNHNQEYFEINTSTGCTSFTASPPASPPTSSVGTTEVKNEGTNHTDDLSRQDDNDPPKEY
  DPGQFAGLLHGSSPACESPENPFHLYGKREQCEKGQDEVSLANSPLPFKQSPIENNSEPL
  VKKIKPKVVSRTIFHKKSNQLENHTIVGTRSTRSGSRNGDQWVMNAGGFVERACTLGRIR
  SLPKALIDMHLSKSVSKSDSDLIAYPSNEKTSRVNWSESSTAEHSSKGNSERTPSFTSEW
  EEIDKIMSSIDVGINNELKEMNGETTRPRCPVQTVGQWLESIGLPQYENHLMANGFDNVQ
  FMGSNVMEDQDLLEIGILNSGHRQRILQAIQLLPKMRPIGHDGYHPTSVAEWLDSIELGD
  YTKAFLINGYTSMDLLKKIWEVELINVLKINLIGHRKRILASLGDRLHDDPPQKPPRSIT
  LREPSGNHTPPQLSPSLSQSTYTTGGSLDVPHIIMQGDARRRRNENYFDDIPRSKLERQM
  AQTGDWGEPSITLRPPNEATASTPVQYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTES
  TQDACAKMRANCQKSTEQMKKVPTIILSVSYKGVKFIDATNKNIIAEHEIRNISCAAQDP
  EDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKGGHSST
  LPESFENKPSKPIPKPRVSIRKSVDLLHASHTGQEPSERHTEEALRKF
• Function: Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells.; Isoform 3 can regulate global protein synthesis by altering nucleolar numbers; Isoform 4 may play a role as a modulator of APP processing. Overexpression can down-regulate APP processing.
• Tissue Specificity: Highly expressed in marrow from patients with pre-B ALL associated with the t(1;19) translocation. Strongly expressed in brain and testis. Expressed in fetal brain. Isoform 4 is highly expressed in brain (at protein level). Isoform 6 is expressed in brain and several cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[1]
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[4]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Cardiac failure	DISDC067	Strong	Genetic Variation	[6]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[7]
Heroin dependence	DISQ1H57	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[5]
Stroke	DISX6UHX	Strong	Genetic Variation	[4]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[9]
Wilson disease	DISVS9H7	Strong	Biomarker	[10]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[2]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[2]
Complex neurodevelopmental disorder	DISB9AFI	Moderate	Autosomal dominant	[5]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[11]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[12]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[19]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[20]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[22]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[24]

4 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 Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B).	[21]

References

• [1] The genetic background difference between diabetic patients with and without nephropathy in a Taiwanese population by linkage disequilibrium mapping using 382 autosomal STR markers.Genet Test Mol Biomarkers. 2010 Jun;14(3):433-8. doi: 10.1089/gtmb.2009.0179.
• [2] Identification of novel risk loci with shared effects on alcoholism, heroin, and methamphetamine dependence.Mol Psychiatry. 2021 Apr;26(4):1152-1161. doi: 10.1038/s41380-019-0497-y. Epub 2019 Aug 28.
• [3] The intracellular localization of amyloid beta protein precursor (AbetaPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AbetaPP and alternative splicing.J Alzheimers Dis. 2004 Feb;6(1):67-78. doi: 10.3233/jad-2004-6108.
• [4] Association of frequent genetic variants in platelet activation pathway genes with large-vessel ischemic stroke in Polish population.Platelets. 2017 Jan;28(1):66-73. doi: 10.1080/09537104.2016.1203404. Epub 2016 Aug 17.
• [5] Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. Nat Commun. 2019 Aug 6;10(1):3529. doi: 10.1038/s41467-019-11437-w.
• [6] Genetics of heart rate in heart failure patients (GenHRate).Hum Genomics. 2019 May 21;13(1):22. doi: 10.1186/s40246-019-0206-6.
• [7] Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.Br J Cancer. 1998 Nov;78(10):1356-60. doi: 10.1038/bjc.1998.684.
• [8] Clinical relevance of cytoskeleton associated proteins for ovarian cancer.J Cancer Res Clin Oncol. 2018 Nov;144(11):2195-2205. doi: 10.1007/s00432-018-2710-9. Epub 2018 Aug 9.
• [9] EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.Oncotarget. 2017 Jul 4;8(33):54939-54950. doi: 10.18632/oncotarget.18978. eCollection 2017 Aug 15.
• [10] The early molecular processes underlying the neurological manifestations of an animal model of Wilson's disease.Metallomics. 2013 May;5(5):532-40. doi: 10.1039/c3mt20243g. Epub 2013 Mar 21.
• [11] End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.Clin Chim Acta. 2016 Aug 1;459:45-52. doi: 10.1016/j.cca.2016.05.012. Epub 2016 May 18.
• [12] 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.
• [13] rs7968606 polymorphism of ANKS1B is associated with improvement in the PANSS general score of schizophrenia caused by amisulpride.Hum Psychopharmacol. 2017 Mar;32(2). doi: 10.1002/hup.2562. Epub 2017 Mar 23.
• [14] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [15] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [16] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [17] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [18] 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.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] 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.
• [22] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [25] 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.