Details of Drug Off-Target (DOT)

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

• DOT Name: Syntaxin-binding protein 6 (STXBP6)
• Synonyms: Amisyn
• Gene Name: STXBP6
• Related Disease:
  Autism
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Rheumatoid arthritis
  Type-1/2 diabetes
• UniProt ID: STXB6_HUMAN
• Pfam ID: PF15277 ; PF00957
• Sequence:
  MSAKSAISKEIFAPLDERMLGAVQVKRRTKKKIPFLATGGQGEYLTYICLSVTNKKPTQA
  SITKVKQFEGSTSFVRRSQWMLEQLRQVNGIDPNGDSAEFDLLFENAFDQWVASTASEKC
  TFFQILHHTCQRYLTDRKPEFINCQSKIMGGNSILHSAADSVTSAVQKASQALNERGERL
  GRAEEKTEDLKNSAQQFAETAHKLAMKHKC
• Function: Forms non-fusogenic complexes with SNAP25 and STX1A and may thereby modulate the formation of functional SNARE complexes and exocytosis.
• Tissue Specificity: Detected at low levels in brain, and at very low levels in heart, adrenal gland, testis, liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Limited	Posttranslational Modification	[2]
Lung cancer	DISCM4YA	Limited	Posttranslational Modification	[2]
Lung carcinoma	DISTR26C	Limited	Posttranslational Modification	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[3]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Syntaxin-binding protein 6 (STXBP6) affects the response to substance of DTI-015.	[22]

17 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 Syntaxin-binding protein 6 (STXBP6).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[11]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[12]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Syntaxin-binding protein 6 (STXBP6).	[13]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Syntaxin-binding protein 6 (STXBP6).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntaxin-binding protein 6 (STXBP6).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Syntaxin-binding protein 6 (STXBP6).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Syntaxin-binding protein 6 (STXBP6).	[21]

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 Syntaxin-binding protein 6 (STXBP6).	[17]

References

• [1] SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles.Hum Mol Genet. 2010 Apr 1;19(7):1368-78. doi: 10.1093/hmg/ddq013. Epub 2010 Jan 12.
• [2] Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma.Sci Rep. 2017 Feb 15;7:42573. doi: 10.1038/srep42573.
• [3] CD6 and syntaxin binding protein 6 variants and response to tumor necrosis factor alpha inhibitors in Danish patients with rheumatoid arthritis.PLoS One. 2012;7(6):e38539. doi: 10.1371/journal.pone.0038539. Epub 2012 Jun 7.
• [4] Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion.Diabetes. 2016 Jul;65(7):1952-61. doi: 10.2337/db15-1489. Epub 2016 Mar 18.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [13] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [14] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [22] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.