Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM7TAOE)

• DOT Name: Syntaxin-16 (STX16)
• Synonyms: Syn16
• Gene Name: STX16
• Related Disease:
  Autism spectrum disorder
  Megalencephaly
  Obesity
  Pseudohypoparathyroidism type 1A
  Pseudohypoparathyroidism type 1B
  Vitamin D deficiency
• UniProt ID: STX16_HUMAN
• Pfam ID: PF05739 ; PF00804
• Sequence:
  MATRRLTDAFLLLRNNSIQNRQLLAEQVSSHITSSPLHSRSIAAELDELADDRMALVSGI
  SLDPEAAIGVTKRPPPKWVDGVDEIQYDVGRIKQKMKELASLHDKHLNRPTLDDSSEEEH
  AIEITTQEITQLFHRCQRAVQALPSRARACSEQEGRLLGNVVASLAQALQELSTSFRHAQ
  SGYLKRMKNREERSQHFFDTSVPLMDDGDDNTLYHRGFTEDQLVLVEQNTLMVEEREREI
  RQIVQSISDLNEIFRDLGAMIVEQGTVLDRIDYNVEQSCIKTEDGLKQLHKAEQYQKKNR
  KMLVILILFVIIIVLIVVLVGVKSR
• Function: SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  Intra-Golgi traffic (R-HSA-6811438)

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 spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Megalencephaly	DISYW5SV	Strong	Genetic Variation	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]
Pseudohypoparathyroidism type 1A	DISSOR3M	Strong	Posttranslational Modification	[3]
Pseudohypoparathyroidism type 1B	DIS9LDXL	Strong	Autosomal dominant	[4]
Vitamin D deficiency	DISAWKYI	Disputed	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Syntaxin-16 (STX16).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Syntaxin-16 (STX16).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Syntaxin-16 (STX16).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Syntaxin-16 (STX16).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-16 (STX16).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Syntaxin-16 (STX16).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntaxin-16 (STX16).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Syntaxin-16 (STX16).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Syntaxin-16 (STX16).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Syntaxin-16 (STX16).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Syntaxin-16 (STX16).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntaxin-16 (STX16).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Syntaxin-16 (STX16).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Syntaxin-16 (STX16).	[17]

References

• [1] Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders.Transl Psychiatry. 2016 Jul 12;6(7):e855. doi: 10.1038/tp.2016.120.
• [2] Macrosomia, obesity, and macrocephaly as first clinical presentation of PHP1b caused by STX16 deletion.Am J Med Genet A. 2016 Sep;170(9):2431-5. doi: 10.1002/ajmg.a.37818. Epub 2016 Jun 23.
• [3] Pseudohypoparathyroidism and GNAS epigenetic defects: clinical evaluation of albright hereditary osteodystrophy and molecular analysis in 40 patients.J Clin Endocrinol Metab. 2010 Feb;95(2):651-8. doi: 10.1210/jc.2009-0176. Epub 2010 Jan 8.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] Autosomal dominant pseudohypoparathyroidism type Ib: a novel inherited deletion ablating STX16 causes loss of imprinting at the A/B DMR.J Clin Endocrinol Metab. 2014 Apr;99(4):E724-8. doi: 10.1210/jc.2013-3704. Epub 2014 Jan 17.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 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.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [15] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.