Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBHQK29)

• DOT Name: IQ motif and SEC7 domain-containing protein 3 (IQSEC3)
• Gene Name: IQSEC3
• Related Disease: Intellectual disability
• UniProt ID: IQEC3_HUMAN
• Pfam ID: PF16453 ; PF01369
• Sequence:
  MESLLENPVRAVLYLKELTAIVQNQQSLIHTQRERIDELERRLDELSAENRSLWEHQQLL
  QAQPPPGLVPPSSAPLPAAPATAPAAAARAQEPLQDQGQRSAAAPHPAPDRPPRQHHGQL
  LEQPQRGPGSRAHTPQSPHKHLGTQGAVTDKEKERPPSCCAAAGALLQHKSPSALGKGVL
  SRRPENETVLHQFCCPAADACSDLASQSDGSCTQAGGGMEDSVVAAAAVAAGRPSAHAPK
  AQAQELQEEEERPGAGAASPRAGPQHKASPGRQQPALATALCPHAPAASDYELSLDLKNK
  QIEMLEHKYGGHLVSRRAACTIQTAFRQYQLSKNFEKIRNSLLESRLPRRISLRKVRSPT
  AESLAAEKALMEGYGLVGLPLVRSPSLPPTFAGTLTELEDSFTEQVQSLAKSIDDALSTW
  SLKTMCSLRESGAYQLHQALQAAAGPPGLEAEGRAPESAGPGPGDDAAETPGLPPAHSGT
  LMMAFRDVTVQIANQNISVSSSTALSVANCLGAQTVQAPAEPAAGKAEQGETSGREAPEA
  PAVGREDASAEDSCAEAAASGAADGATAPKTEEEEEEEETAEVGRGAEAEAGDLEQLSSS
  STSTKSAKSGSEASASASKDALQAMILSLPRYHCENPASCKSPTLSTDTLRKRLYRIGLN
  LFNINPDKGIQFLISRGFIPDTPIGVAHFLLQRKGLSRQMIGEFLGNSKKQFNRDVLDCV
  VDEMDFSSMELDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCMCNPEVVQQFHNPDTIF
  ILAFAIILLNTDMYSPNIKPDRKMMLEDFIRNLRGVDDGADIPRELVVGIYERIQQKELK
  SNEDHVTYVTKVEKSIVGMKTVLSVPHRRLVCCSRLFEVTDVNKLQKQAAHQREVFLFND
  LLVILKLCPKKKSSSTYTFCKSVGLLGMQFQLFENEYYSHGITLVTPLSGSEKKQVLHFC
  ALGSDEMQKFVEDLKESIAEVTELEQIRIEWELEKQQGTKTLSFKPCGAQGDPQSKQGSP
  TAKREAALRERPAESTVEVSIHNRLQTSQHNSGLGAERGAPVPPPDLQPSPPRQQTPPLP
  PPPPTPPGTLVQCQQIVKVIVLDKPCLARMEPLLSQALSCYTSSSSDSCGSTPLGGPGSP
  VKVTHQPPLPPPPPPYNHPHQFCPPGSLLHGHRYSSGSRSLV
• Function: Acts as a guanine nucleotide exchange factor (GEF) for ARF1.
• Tissue Specificity: Expressed specifically in the adult brain, predominantly in the cerebral cortex and the olfactory bulb, but not in the fetal brain. Expressed only in mature neurons, but not in undifferentiated neural stem precursor cells (NSPCs), nor in glioma cells.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway: NPAS4 regulates expression of target genes (R-HSA-9768919)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]

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 IQ motif and SEC7 domain-containing protein 3 (IQSEC3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of IQ motif and SEC7 domain-containing protein 3 (IQSEC3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of IQ motif and SEC7 domain-containing protein 3 (IQSEC3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of IQ motif and SEC7 domain-containing protein 3 (IQSEC3).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of IQ motif and SEC7 domain-containing protein 3 (IQSEC3).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of IQ motif and SEC7 domain-containing protein 3 (IQSEC3).	[5]

References

• [1] Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.Am J Hum Genet. 2019 Jun 6;104(6):1182-1201. doi: 10.1016/j.ajhg.2019.04.011. Epub 2019 May 23.
• [2] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] 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.
• [7] 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.