Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT23FQIB)

• DOT Name: Astrotactin-1 (ASTN1)
• Gene Name: ASTN1
• Related Disease:
  Narcolepsy
  Advanced cancer
  Alcohol dependence
  Atopic dermatitis
  Bipolar disorder
  Brain disease
  Cervical cancer
  Cervical carcinoma
  Epilepsy
  Intellectual disability
  Major depressive disorder
  Neurodevelopmental disorder
  Schizophrenia
  Substance abuse
  Autism
• UniProt ID: ASTN1_HUMAN
• Pfam ID: PF18411 ; PF19743 ; PF19441
• Sequence:
  MALAGLCALLACCWGPAAVLATAAGDVDPSKELECKLKSITVSALPFLRENDLSIMHSPS
  ASEPKLLFSVRNDFPGEMVVVDDLENTELPYFVLEISGNTEDIPLVRWRQQWLENGTLLF
  HIHHQDGAPSLPGQDPTEEPQHESAEEELRILHISVMGGMIALLLSILCLVMILYTRRRW
  CKRRRVPQPQKSASAEAANEIHYIPSVLIGGHGRESLRNARVQGHNSSGTLSIRETPILD
  GYEYDITDLRHHLQRECMNGGEDFASQVTRTLDSLQGCNEKSGMDLTPGSDNAKLSLMNK
  YKDNIIATSPVDSNHQQATLLSHTSSSQRKRINNKARAGSAFLNPEGDSGTEAENDPQLT
  FYTDPSRSRRRSRVGSPRSPVNKTTLTLISITSCVIGLVCSSHVNCPLVVKITLHVPEHL
  IADGSRFILLEGSQLDASDWLNPAQVVLFSQQNSSGPWAMDLCARRLLDPCEHQCDPETG
  RREHRAAGECLCYEGYMKDPVHKHLCIRNEWGTNQGPWPYTIFQRGFDLVLGEQPSDKIF
  RFTYTLGEGMWLPLSKSFVIPPAELAINPSAKCKTDMTVMEDAVEVREELMTSSSFDSLE
  VLLDSFGPVRDCSKDNGGCSKNFRCISDRKLDSTGCVCPSGLSPMKDSSGCYDRHIGVDC
  SDGFNGGCEQLCLQQMAPFPDDPTLYNILMFCGCIEDYKLGVDGRSCQLITETCPEGSDC
  GESRELPMNQTLFGEMFFGYNNHSKEVAAGQVLKGTFRQNNFARGLDQQLPDGLVVATVP
  LENQCLEEISEPTPDPDFLTGMVNFSEVSGYPVLQHWKVRSVMYHIKLNQVAISQALSNA
  LHSLDGATSRADFVALLDQFGNHYIQEAIYGFEESCSIWYPNKQVQRRLWLEYEDISKGN
  SPSDESEERERDPKVLTFPEYITSLSDSGTKHMAAGVRMECHSKGRCPSSCPLCHVTSSP
  DTPAEPVLLEVTKAAPIYELVTNNQTQRLLQEATMSSLWCSGTGDVIEDWCRCDSTAFGA
  DGLPTCAPLPQPVLRLSTVHEPSSTLVVLEWEHSEPPIGVQIVDYLLRQEKVTDRMDHSK
  VETETVLSFVDDIISGAKSPCAMPSQVPDKQLTTISLIIRCLEPDTIYMFTLWGVDNTGR
  RSRPSDVIVKTPCPVVDDVKAQEIADKIYNLFNGYTSGKEQQTAYNTLLDLGSPTLHRVL
  YHYNQHYESFGEFTWRCEDELGPRKAGLILSQLGDLSSWCNGLLQEPKISLRRSSLKYLG
  CRYSEIKPYGLDWAELSRDLRKTCEEQTLSIPYNDYGDSKEI
• Function: Neuronal adhesion molecule that is required for normal migration of young postmitotic neuroblasts along glial fibers, especially in the cerebellum. Required for normal rate of migration of granule cells during brain development and for normal cerebellum development.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[3]
Brain disease	DIS6ZC3X	Strong	Genetic Variation	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Epilepsy	DISBB28L	Strong	Biomarker	[6]
Intellectual disability	DISMBNXP	Strong	Biomarker	[6]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[7]
Neurodevelopmental disorder	DIS372XH	Strong	Altered Expression	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Substance abuse	DIS327VW	Strong	Genetic Variation	[3]
Autism	DISV4V1Z	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Astrotactin-1 (ASTN1) affects the response to substance of Cisplatin.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Astrotactin-1 (ASTN1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Astrotactin-1 (ASTN1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Astrotactin-1 (ASTN1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Astrotactin-1 (ASTN1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Astrotactin-1 (ASTN1).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Astrotactin-1 (ASTN1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Astrotactin-1 (ASTN1).	[14]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Astrotactin-1 (ASTN1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Astrotactin-1 (ASTN1).	[17]

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 Astrotactin-1 (ASTN1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Astrotactin-1 (ASTN1).	[16]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] Cleave but not leave: Astrotactin proteins in development and disease.IUBMB Life. 2017 Aug;69(8):572-577. doi: 10.1002/iub.1641. Epub 2017 May 18.
• [3] ASTN1 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.Am J Med Genet B Neuropsychiatr Genet. 2012 Jun;159B(4):445-55. doi: 10.1002/ajmg.b.32048. Epub 2012 Apr 9.
• [4] Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide, astrotactin 1-derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis-like and psoriasis-like dermatitis.J Allergy Clin Immunol. 2018 Jan;141(1):137-151. doi: 10.1016/j.jaci.2017.04.007. Epub 2017 Apr 26.
• [5] Performance of a DNA methylation marker panel using liquid-based cervical scrapes to detect cervical cancer and its precancerous stages.BMC Cancer. 2018 Dec 3;18(1):1197. doi: 10.1186/s12885-018-5125-8.
• [6] Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. Neuron. 2015 Nov 4;88(3):499-513. doi: 10.1016/j.neuron.2015.09.048.
• [7] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways.Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.
• [8] ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins.Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9717-E9726. doi: 10.1073/pnas.1809382115. Epub 2018 Sep 21.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [16] 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.
• [17] 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.
• [18] 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.