Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJMJZW8)

• DOT Name: Autophagy-related protein 9B (ATG9B)
• Synonyms: APG9-like 2; Nitric oxide synthase 3-overlapping antisense gene protein; Protein sONE
• Gene Name: ATG9B
• Related Disease:
  Oral lichen planus
  Clear cell renal carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: ATG9B_HUMAN
• PDB ID: 8POE
• Pfam ID: PF04109
• Sequence:
  MVSRMGWGGRRRRLGRWGDLGPGSVPLLPMPLPPPPPPSCRGPGGGRISIFSLSPAPHTR
  SSPSSFSPPTAGPPCSVLQGTGASQSCHSALPIPATPPTQAQPAMTPASASPSWGSHSTP
  PLAPATPTPSQQCPQDSPGLRVGPLIPEQDYERLEDCDPEGSQDSPIHGEEQQPLLHVPE
  GLRGSWHHIQNLDSFFTKIYSYHQRNGFACILLEDVFQLGQFIFIVTFTTFLLRCVDYNV
  LFANQPSNHTRPGPFHSKVTLSDAILPSAQCAERIRSSPLLVLLLVLAAGFWLVQLLRSV
  CNLFSYWDIQVFYREALHIPPEELSSVPWAEVQSRLLALQRSGGLCVQPRPLTELDIHHR
  ILRYTNYQVALANKGLLPARCPLPWGGSAAFLSRGLALNVDLLLFRGPFSLFRGGWELPH
  AYKRSDQRGALAARWGRTVLLLAALNLALSPLVLAWQVLHVFYSHVELLRREPGALGARG
  WSRLARLQLRHFNELPHELRARLARAYRPAAAFLRTAAPPAPLRTLLARQLVFFAGALFA
  ALLVLTVYDEDVLAVEHVLTAMTALGVTATVARSFIPEEQCQGRAPQLLLQTALAHMHYL
  PEEPGPGGRDRAYRQMAQLLQYRAVSLLEELLSPLLTPLFLLFWFRPRALEIIDFFHHFT
  VDVAGVGDICSFALMDVKRHGHPQWLSAGQTEASLSQRAEDGKTELSLMRFSLAHPLWRP
  PGHSSKFLGHLWGRVQQDAAAWGATSARGPSTPGVLSNCTSPLPEAFLANLFVHPLLPPR
  DLSPTAPCPAAATASLLASISRIAQDPSSVSPGGTGGQKLAQLPELASAEMSLHVIYLHQ
  LHQQQQQQEPWGEAAASILSRPCSSPSQPPSPDEEKPSWSSDGSSPASSPRQQWGTQKAR
  NLFPGGFQVTTDTQKEPDRASCTD
• Function: Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion. Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome. Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion. In addition to autophagy, also plays a role in necrotic cell death.
• Tissue Specificity: Highly expressed in placenta (trophoblast cells) and pituitary gland. Not expressed in vascular endothelial.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
• Reactome Pathway: Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral lichen planus	DISVEAJA	Definitive	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[3]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[3]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[3]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Autophagy-related protein 9B (ATG9B).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Autophagy-related protein 9B (ATG9B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Autophagy-related protein 9B (ATG9B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Autophagy-related protein 9B (ATG9B).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Autophagy-related protein 9B (ATG9B).	[7]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Autophagy-related protein 9B (ATG9B).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Autophagy-related protein 9B (ATG9B).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Autophagy-related protein 9B (ATG9B).	[11]

References

• [1] Altered Autophagy-Associated Genes Expression in T Cells of Oral Lichen Planus Correlated with Clinical Features.Mediators Inflamm. 2016;2016:4867368. doi: 10.1155/2016/4867368. Epub 2016 Feb 15.
• [2] The role of CRP and ATG9B expression in clear cell renal cell carcinoma.Biosci Rep. 2017 Nov 15;37(6):BSR20171082. doi: 10.1042/BSR20171082. Print 2017 Dec 22.
• [3] Comprehensive analysis of the clinical significance and prospective molecular mechanisms of differentially expressed autophagy-related genes in thyroid cancer.Int J Oncol. 2018 Aug;53(2):603-619. doi: 10.3892/ijo.2018.4404. Epub 2018 May 11.
• [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] 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.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] TNF enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy. Toxicol Lett. 2021 May 15;342:73-84. doi: 10.1016/j.toxlet.2021.02.009. Epub 2021 Feb 17.
• [9] 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.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.