Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTJHX9A)

• DOT Name: t-SNARE domain-containing protein 1 (TSNARE1)
• Gene Name: TSNARE1
• Related Disease:
  Anxiety
  Major depressive disorder
  Schizophrenia
• UniProt ID: TSNA1_HUMAN
• Pfam ID: PF13873 ; PF05739 ; PF14523
• Sequence:
  MSYGSIARGGGLGSRGPFGGPSRQGCQPLECARCWTEYGIRHFPCPSPESKLQNRCVGKD
  GEGDLGPAGTPIVPRARKRGPGVAPEGSRMPEPTSSPTIGPRKDSAAGPHGRMAGPSTTR
  AKKRKPNFCPQETEVLVSKVSKHHQLLFGTGLLKAEPTRRYRVWSRILQAVNALGYCRRD
  VVDLKHKWRDLRAVVRRKLGDLRKAAHGPSPGSGKPQALALTPVEQVVAKTFSCQALPSE
  GFSLEPPRATQVDPCNLQELFQEMSANVFRINSSVTSLERSLQSLGTPSDTQELRDSLHT
  AQQETNKTIAASASSVKQMAELLRSSCPQERLQQERPQLDRLKTQLSDAIQCYGVVQKKI
  AEKSRALLPMAQRGSKQSPQAPFAELADDEKVFNGSDNMWQGQEQALLPDITEEDLEAIR
  LREEAILQMESNLLDVNQIIKDLASMVSEQGEAVDSIEASLEAASSHAEAARQLLAGASR
  HQLQRHKIKCCFLSAGVTALLVIIIIIATSVRK

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Genetic Variation	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[3]

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 t-SNARE domain-containing protein 1 (TSNARE1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of t-SNARE domain-containing protein 1 (TSNARE1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of t-SNARE domain-containing protein 1 (TSNARE1).	[8]

2 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 t-SNARE domain-containing protein 1 (TSNARE1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of t-SNARE domain-containing protein 1 (TSNARE1).	[7]

References

• [1] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [2] Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.Mol Psychiatry. 2020 Jul;25(7):1420-1429. doi: 10.1038/s41380-018-0336-6. Epub 2019 Jan 9.
• [3] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [4] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] 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.