Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZLRZ55)

• DOT Name: Late secretory pathway protein AVL9 homolog (AVL9)
• Gene Name: AVL9
• Related Disease:
  Juvenile idiopathic arthritis
  Osteoarthritis
  Clear cell renal carcinoma
  Renal cell carcinoma
• UniProt ID: AVL9_HUMAN
• Pfam ID: PF09794
• Sequence:
  MEKARRGGDGVPRGPVLHIVVVGFHHKKGCQVEFSYPPLIPGDGHDSHTLPEEWKYLPFL
  ALPDGAHNYQEDTVFFHLPPRNGNGATVFGISCYRQIEAKALKVRQADITRETVQKSVCV
  LSKLPLYGLLQAKLQLITHAYFEEKDFSQISILKELYEHMNSSLGGASLEGSQVYLGLSP
  RDLVLHFRHKVLILFKLILLEKKVLFYISPVNKLVGALMTVLSLFPGMIEHGLSDCSQYR
  PRKSMSEDGGLQESNPCADDFVSASTADVSHTNLGTIRKVMAGNHGEDAAMKTEEPLFQV
  EDSSKGQEPNDTNQYLKPPSRPSPDSSESDWETLDPSVLEDPNLKEREQLGSDQTNLFPK
  DSVPSESLPITVQPQANTGQVVLIPGLISGLEEDQYGMPLAIFTKGYLCLPYMALQQHHL
  LSDVTVRGFVAGATNILFRQQKHLSDAIVEVEEALIQIHDPELRKLLNPTTADLRFADYL
  VRHVTENRDDVFLDGTGWEGGDEWIRAQFAVYIHALLAATLQLDNEKILSDYGTTFVTAW
  KNTHNYRVWNSNKHPALAEINPNHPFQGQYSVSDMKLRFSHSVQNSERGKKIGNVMVTTS
  RNVVQTGKAVGQSVGGAFSSAKTAMSSWLSTFTTSTSQSLTEPPDEKP
• Function: Functions in cell migration.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[2]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[3]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[3]

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 Late secretory pathway protein AVL9 homolog (AVL9).	[4]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Late secretory pathway protein AVL9 homolog (AVL9).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Late secretory pathway protein AVL9 homolog (AVL9).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Late secretory pathway protein AVL9 homolog (AVL9).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Late secretory pathway protein AVL9 homolog (AVL9).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Late secretory pathway protein AVL9 homolog (AVL9).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Late secretory pathway protein AVL9 homolog (AVL9).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Late secretory pathway protein AVL9 homolog (AVL9).	[10]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [2] Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.Lancet. 2012 Sep 1;380(9844):815-23. doi: 10.1016/S0140-6736(12)60681-3. Epub 2012 Jul 3.
• [3] Hypoxia-regulated lncRNA CRPAT4 promotes cell migration via regulating AVL9 in clear cell renal cell carcinomas.Onco Targets Ther. 2018 Aug 3;11:4537-4545. doi: 10.2147/OTT.S169155. eCollection 2018.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.