Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFD17IL)

• DOT Name: Exocyst complex component 3-like protein 4 (EXOC3L4)
• Gene Name: EXOC3L4
• Related Disease:
  Alzheimer disease
  Primary biliary cholangitis
• UniProt ID: EX3L4_HUMAN
• Pfam ID: PF06046
• Sequence:
  MPSPQTDTPGPELQSPKEAEEPQTPAQGSRRTSSRKEPNAHRKDGTRLGLGSLRQAFSRA
  SQRALTQVSKEDTGLFRRSSCSLFRSFRQALNDGPATGHSQATPEVPSGVMNGVSQQAST
  GAASEELKPEAEGKSVADLITERQLLAAFEQLLRLETLLVAEKASRTFEQDPTAFARRAM
  DVCLLYDGLAAEIGAIVRETLDSDGVDAAALAELARVVSAEEEAHPSPPDDGDFLRTPRR
  WRQHWEEAVRRSAQERVRRPGAGWAFGEAEGASGLAQLLAELGGLVRRDLQKVRQEVQPA
  YAAAGFPAWEVYLRAFHSAVAQRLQELARDARGCEQLYILLDWAANVYGSPDFLGAPGLA
  LPAEPLPPLLAPDVWARLESDYTSFLEAKIASCFDSILQLEQSHWAAAEVPEVLQGLYQA
  PLSMDVHMLVAEHVKAAGAISAELEATTLRICTRALGLFVPRFEKAFLASEAVSEPHLGA
  YINACEELRTSLLSRFPGTQEELEKPLVTATCSFQKHLLQGLQRELQPLFRVVCTRDWLT
  QDWLHPLMDKVVTFAGHLQRVARPRAQETLQEVHRFVVREYLARALRPRERFRGMERMHG
  SQKMSLDAQAISDTFQGLGSEATWLDQAIQCVAEILGETYKDDIQRHLETLIRSYPDIRR
  DHILAILALRRLGRQRNQHLLQHTQDLLRAAAGAAGAEAPRGRVLFEEIKVPSAMAVLIT
  CV

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[2]

2 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 Exocyst complex component 3-like protein 4 (EXOC3L4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Exocyst complex component 3-like protein 4 (EXOC3L4).	[9]

5 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 Exocyst complex component 3-like protein 4 (EXOC3L4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Exocyst complex component 3-like protein 4 (EXOC3L4).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Exocyst complex component 3-like protein 4 (EXOC3L4).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Exocyst complex component 3-like protein 4 (EXOC3L4).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Exocyst complex component 3-like protein 4 (EXOC3L4).	[8]

References

• [1] Rare variants in the splicing regulatory elements of EXOC3L4 are associated with brain glucose metabolism in Alzheimer's disease.BMC Med Genomics. 2018 Sep 14;11(Suppl 3):76. doi: 10.1186/s12920-018-0390-6.
• [2] International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.Nat Commun. 2015 Sep 22;6:8019. doi: 10.1038/ncomms9019.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.