Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXZD3DG)

• DOT Name: ADP-ribosylation factor-like protein 17 (ARL17B)
• Synonyms: ADP-ribosylation factor 7 variant
• Gene Name: ARL17B
• Related Disease:
  Alzheimer disease
  Breast carcinoma
  Progressive supranuclear palsy
  Androgenetic alopecia
  Baldness, male pattern
• UniProt ID: ARL17_HUMAN
• Pfam ID: PF00025 ; PF15840
• Sequence:
  MGNIFEKLFKSLLGKKKMRILILSLDTAGKTTILYKLKLGETVPAVPTVGFCVETVEYKN
  NTFAVWDVGSHFKIRPLWQHFFQNTKGARSPGSTHQGSLASGVLPIKCSHVEFGMWKGGR
  SHPFLPHSSRCAGSGGQLDSILPHQSPAWGPWGCKDLSSGFPSFLTSSILWKSAVVK
• Function: GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Progressive supranuclear palsy	DISO5KRQ	Strong	Biomarker	[3]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[4]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[4]

8 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 ADP-ribosylation factor-like protein 17 (ARL17B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of ADP-ribosylation factor-like protein 17 (ARL17B).	[13]

1 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 ADP-ribosylation factor-like protein 17 (ARL17B).	[8]

References

• [1] Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.Alzheimers Dement. 2019 Oct;15(10):1333-1347. doi: 10.1016/j.jalz.2019.06.4950. Epub 2019 Aug 28.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] Gene expression, methylation and neuropathology correlations at progressive supranuclear palsy risk loci.Acta Neuropathol. 2016 Aug;132(2):197-211. doi: 10.1007/s00401-016-1576-7. Epub 2016 Apr 26.
• [4] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells. Environ Mol Mutagen. 2009 Mar;50(2):134-44.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.