Details of Drug Off-Target (DOT)

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

• DOT Name: Ataxin-10 (ATXN10)
• Synonyms: Brain protein E46 homolog; Spinocerebellar ataxia type 10 protein
• Gene Name: ATXN10
• Related Disease:
  Autosomal recessive spinocerebellar ataxia 10
  Cardiac arrest
  Cerebellar ataxia
  Dentatorubral-pallidoluysian atrophy
  Friedreich's ataxia
  Parkinson disease
  Sleep disorder
  Spinocerebellar ataxia type 10
  Spinocerebellar ataxia type 3
  Spinocerebellar ataxia type 36
  Choreatic disease
  Fragile X-associated tremor/ataxia syndrome
  Huntington disease-like 2
  Myotonic dystrophy type 2
  Nephronophthisis
• UniProt ID: ATX10_HUMAN
• Pfam ID: PF09759
• Sequence:
  MAAPRPPPARLSGVMVPAPIQDLEALRALTALFKEQRNRETAPRTIFQRVLDILKKSSHA
  VELACRDPSQVENLASSLQLITECFRCLRNACIECSVNQNSIRNLDTIGVAVDLILLFRE
  LRVEQESLLTAFRCGLQFLGNIASRNEDSQSIVWVHAFPELFLSCLNHPDKKIVAYSSMI
  LFTSLNHERMKELEENLNIAIDVIDAYQKHPESEWPFLIITDLFLKSPELVQAMFPKLNN
  QERVTLLDLMIAKITSDEPLTKDDIPVFLRHAELIASTFVDQCKTVLKLASEEPPDDEEA
  LATIRLLDVLCEMTVNTELLGYLQVFPGLLERVIDLLRVIHVAGKETTNIFSNCGCVRAE
  GDISNVANGFKSHLIRLIGNLCYKNKDNQDKVNELDGIPLILDNCNISDSNPFLTQWVIY
  AIRNLTEDNSQNQDLIAKMEEQGLADASLLKKVGFEVEKKGEKLILKSTRDTPKP
• Function: Necessary for the survival of cerebellar neurons. Induces neuritogenesis by activating the Ras-MAP kinase pathway. May play a role in the maintenance of a critical intracellular glycosylation level and homeostasis.
• Tissue Specificity: Expressed in the central nervous system.
• KEGG Pathway: Spinocerebellar ataxia (hsa05017)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive spinocerebellar ataxia 10	DISAQ91A	Strong	Genetic Variation	[1]
Cardiac arrest	DIS9DIA4	Strong	Biomarker	[2]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[3]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Genetic Variation	[4]
Friedreich's ataxia	DIS5DV35	Strong	Biomarker	[5]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[6]
Spinocerebellar ataxia type 10	DISEJVJK	Strong	Autosomal dominant	[7]
Spinocerebellar ataxia type 3	DISQBQID	Strong	Biomarker	[8]
Spinocerebellar ataxia type 36	DISP7IPL	Strong	Genetic Variation	[9]
Choreatic disease	DISH8K3M	moderate	Biomarker	[10]
Fragile X-associated tremor/ataxia syndrome	DISKB25R	moderate	Biomarker	[11]
Huntington disease-like 2	DISM3G09	moderate	Biomarker	[11]
Myotonic dystrophy type 2	DIS5ZWF1	moderate	Biomarker	[11]
Nephronophthisis	DISXU4HY	Limited	Biomarker	[12]

1 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 Ataxin-10 (ATXN10).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ataxin-10 (ATXN10).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ataxin-10 (ATXN10).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ataxin-10 (ATXN10).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ataxin-10 (ATXN10).	[17]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Ataxin-10 (ATXN10).	[18]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Ataxin-10 (ATXN10).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ataxin-10 (ATXN10).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ataxin-10 (ATXN10).	[20]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ataxin-10 (ATXN10).	[21]

References

• [1] ANO10 mutations cause ataxia and coenzyme Q deficiency.J Neurol. 2014 Nov;261(11):2192-8. doi: 10.1007/s00415-014-7476-7. Epub 2014 Sep 3.
• [2] Olfactory Function in SCA10.Cerebellum. 2019 Feb;18(1):85-90. doi: 10.1007/s12311-018-0954-1.
• [3] The occurrence of spinocerebellar ataxias caused by dynamic mutations in Polish patients.Neurol Neurochir Pol. 2010 May-Jun;44(3):238-45. doi: 10.1016/s0028-3843(14)60037-2.
• [4] Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent.J Hum Genet. 2016 Mar;61(3):215-22. doi: 10.1038/jhg.2015.131. Epub 2015 Nov 5.
• [5] Detection of large pathogenic expansions in FRDA1, SCA10, and SCA12 genes using a simple fluorescent repeat-primed PCR assay.J Mol Diagn. 2004 May;6(2):96-100. doi: 10.1016/S1525-1578(10)60496-5.
• [6] Sleep disorders in spinocerebellar ataxia type 10.J Sleep Res. 2018 Oct;27(5):e12688. doi: 10.1111/jsr.12688. Epub 2018 Apr 6.
• [7] Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol. 2001 Aug;50(2):234-9. doi: 10.1002/ana.1081.
• [8] Autosomal dominant cerebellar ataxia: frequency analysis and clinical characterization of 45 families from Portugal.Eur J Neurol. 2010 Jan;17(1):124-8. doi: 10.1111/j.1468-1331.2009.02757.x. Epub 2009 Jul 29.
• [9] 'Costa da Morte' ataxia is spinocerebellar ataxia 36: clinical and genetic characterization.Brain. 2012 May;135(Pt 5):1423-35. doi: 10.1093/brain/aws069. Epub 2012 Apr 3.
• [10] Should spinocerebellar ataxias be included in the differential diagnosis for Huntington's diseases-like syndromes?.J Neurol Sci. 2014 Dec 15;347(1-2):356-8. doi: 10.1016/j.jns.2014.09.050. Epub 2014 Oct 8.
• [11] RNA-mediated neuromuscular disorders.Annu Rev Neurosci. 2006;29:259-77. doi: 10.1146/annurev.neuro.29.051605.113014.
• [12] Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011 May 13;145(4):513-28. doi: 10.1016/j.cell.2011.04.019.
• [13] 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.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [21] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.