Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFI1IPG)

• DOT Name: Exocyst complex component 6B (EXOC6B)
• Synonyms: Exocyst complex component Sec15B; SEC15-like protein 2
• Gene Name: EXOC6B
• Related Disease:
  Intellectual disability
  Microcephaly
  Movement disorder
  Myopia
  Pathologic nystagmus
  Pneumococcal meningitis
  Spondyloepimetaphyseal dysplasia with joint laxity, type 3
  Spondyloepimetaphyseal dysplasia with joint laxity
• UniProt ID: EXC6B_HUMAN
• Pfam ID: PF20651 ; PF04091
• Sequence:
  MERGKMAEAESLETAAEHERILREIESTDTACIGPTLRSVYDGEEHGRFMEKLETRIRNH
  DREIEKMCNFHYQGFVDSITELLKVRGEAQKLKNQVTDTNRKLQHEGKELVIAMEELKQC
  RLQQRNISATVDKLMLCLPVLEMYSKLRDQMKTKRHYPALKTLEHLEHTYLPQVSHYRFC
  KVMVDNIPKLREEIKDVSMSDLKDFLESIRKHSDKIGETAMKQAQQQRNLDNIVLQQPRI
  GSKRKSKKDAYIIFDTEIESTSPKSEQDSGILDVEDEEDDEEVPGAQDLVDFSPVYRCLH
  IYSVLGARETFENYYRKQRRKQARLVLQPPSNMHETLDGYRKYFNQIVGFFVVEDHILHT
  TQGLVNRAYIDELWEMALSKTIAALRTHSSYCSDPNLVLDLKNLIVLFADTLQVYGFPVN
  QLFDMLLEIRDQYSETLLKKWAGIFRNILDSDNYSPIPVTSEEMYKKVVGQFPFQDIELE
  KQPFPKKFPFSEFVPKVYNQIKEFIYACLKFSEDLHLSSTEVDDMIRKSTNLLLTRTLSN
  SLQNVIKRKNIGLTELVQIIINTTHLEKSCKYLEEFITNITNVLPETVHTTKLYGTTTFK
  DARHAAEEEIYTNLNQKIDQFLQLADYDWMTGDLGNKASDYLVDLIAFLRSTFAVFTHLP
  GKVAQTACMSACKHLATSLMQLLLEAEVRQLTLGALQQFNLDVRECEQFARSGPVPGFQE
  DTLQLAFIDLRQLLDLFIQWDWSTYLADYGQPNCKYLRVNPVTALTLLEKMKDTSRKNNM
  FAQFRKNERDKQKLIDTVAKQLRGLISSHHS
• Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Microcephaly	DIS2GRD8	Strong	Genetic Variation	[1]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[2]
Myopia	DISK5S60	Strong	Genetic Variation	[1]
Pathologic nystagmus	DIS1QSPO	Strong	Genetic Variation	[1]
Pneumococcal meningitis	DISM5U0L	Strong	Genetic Variation	[3]
Spondyloepimetaphyseal dysplasia with joint laxity, type 3	DIS4Q0EA	Strong	Autosomal recessive	[2]
Spondyloepimetaphyseal dysplasia with joint laxity	DIS94DW9	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Exocyst complex component 6B (EXOC6B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Exocyst complex component 6B (EXOC6B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Exocyst complex component 6B (EXOC6B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Exocyst complex component 6B (EXOC6B).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Exocyst complex component 6B (EXOC6B).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Exocyst complex component 6B (EXOC6B).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Exocyst complex component 6B (EXOC6B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Exocyst complex component 6B (EXOC6B).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Exocyst complex component 6B (EXOC6B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Exocyst complex component 6B (EXOC6B).	[14]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Exocyst complex component 6B (EXOC6B).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Exocyst complex component 6B (EXOC6B).	[15]

References

• [1] Mosaic deletion of EXOC6B: further evidence for an important role of the exocyst complex in the pathogenesis of intellectual disability.Am J Med Genet A. 2014 Dec;164A(12):3088-94. doi: 10.1002/ajmg.a.36770. Epub 2014 Sep 24.
• [2] A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. Eur J Hum Genet. 2016 Aug;24(8):1206-10. doi: 10.1038/ejhg.2015.261. Epub 2015 Dec 16.
• [3] Exome Array Analysis of Susceptibility to Pneumococcal Meningitis.Sci Rep. 2016 Jul 8;6:29351. doi: 10.1038/srep29351.
• [4] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [5] 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.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [12] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.
• [15] 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.