Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5EZO0M)

• DOT Name: Ataxin-7-like protein 1 (ATXN7L1)
• Synonyms: Ataxin-7-like protein 4
• Gene Name: ATXN7L1
• Related Disease:
  Alzheimer disease
  Chronic obstructive pulmonary disease
  Dental caries
  Venous thromboembolism
• UniProt ID: AT7L1_HUMAN
• Pfam ID: PF08313
• Sequence:
  MTSERSRIPCLSAAAAEGTGKKQQEGRAMATLDRKVPSPEAFLGKPWSSWIDAAKLHCSD
  NVDLEEAGKEGGKSREVMRLNKEDMHLFGHYPAHDDFYLVVCSACNQVVKPQVFQSHCER
  RHGSMCRPSPSPVSPASNPRTSLVQVKTKACLSGHHSASSTSKPFKTPKDNLLTSSSKQH
  TVFPAKGSRDKPCVPVPVVSLEKIPNLVKADGANVKMNSTTTTAVSASSTSSSAVSTPPL
  IKPVLMSKSVPPSPEKILNGKGILPTTIDKKHQNGTKNSNKPYRRLSEREFDPNKHCGVL
  DPETKKPCTRSLTCKTHSLSHRRAVPGRKKQFDLLLAEHKAKSREKEVKDKEHLLTSTRE
  ILPSQSGPAQDSLLGSSGSSGPEPKVASPAKSRPPNSVLPRPSSANSISSSTSSNHSGHT
  PEPPLPPVGGDLASRLSSDEGEMDGADESEKLDCQFSTHHPRPLAFCSFGSRLMGRGYYV
  FDRRWDRFRFALNSMVEKHLNSQMWKKIPPAADSPLPSPAAHITTPVPASVLQPFSNPSA
  VYLPSAPISSRLTSSYIMTSAMLSNAAFVTSPDPSALMSHTTAFPHVAATLSIMDSTFKA
  PSAVSPIPAVIPSPSHKPSKTKTSKSSKVKDLSTRSDESPSNKKRKPQSSTSSSSSSSSS
  SLQTSLSSPLSGPHKKNCVLNASSALNSYQAAPPYNSLSVHNSNNGVSPLSAKLEPSGRT
  SLPGGPADIVRQVGAVGGSSDSCPLSVPSLALHAGDLSLASHNAVSSLPLSFDKSEGKKR
  KNSSSSSKACKITKMPGMNSVHKKNPPSLLAPVPDPVNSTSSRQVGKNSSLALSQSSPSS
  ISSPGHSRQNTNRTGRIRTLP

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Dental caries	DISRBCMD	Strong	Genetic Variation	[3]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[4]

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 Ataxin-7-like protein 1 (ATXN7L1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ataxin-7-like protein 1 (ATXN7L1).	[14]

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-7-like protein 1 (ATXN7L1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[11]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ataxin-7-like protein 1 (ATXN7L1).	[15]

References

• [1] Genome-wide association and linkage study in the Amish detects a novel candidate late-onset Alzheimer disease gene.Ann Hum Genet. 2012 Sep;76(5):342-51. doi: 10.1111/j.1469-1809.2012.00721.x.
• [2] The genetics of smoking in individuals with chronic obstructive pulmonary disease.Respir Res. 2018 Apr 10;19(1):59. doi: 10.1186/s12931-018-0762-7.
• [3] GWAS of dental caries patterns in the permanent dentition.J Dent Res. 2013 Jan;92(1):38-44. doi: 10.1177/0022034512463579. Epub 2012 Oct 11.
• [4] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [5] 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.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] 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.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] 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.
• [15] 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.