Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSGYNA5)

• DOT Name: Synapsin-3 (SYN3)
• Synonyms: Synapsin III
• Gene Name: SYN3
• Related Disease:
  Parkinson disease
  Age-related macular degeneration
  Bipolar disorder
  Chronic obstructive pulmonary disease
  Familial focal epilepsy with variable foci
  Multiple sclerosis
  Neovascular age-related macular degeneration
  Benign prostatic hyperplasia
  Anxiety
  Anxiety disorder
  Inflammatory bowel disease
  Neoplasm
  Pyoderma gangrenosum
• UniProt ID: SYN3_HUMAN
• PDB ID: 2P0A
• Pfam ID: PF02078 ; PF02750 ; PF10581
• Sequence:
  MNFLRRRLSDSSFMANLPNGYMTDLQRPDSSTSSPASPAMERRHPQPLAASFSSPGSSLF
  SSLSSAMKQAPQATSGLMEPPGPSTPIVQRPRILLVIDDAHTDWSKYFHGKKVNGEIEIR
  VEQAEFSELNLAAYVTGGCMVDMQVVRNGTKVVSRSFKPDFILVRQHAYSMALGEDYRSL
  VIGLQYGGLPAVNSLYSVYNFCSKPWVFSQLIKIFHSLGPEKFPLVEQTFFPNHKPMVTA
  PHFPVVVKLGHAHAGMGKIKVENQLDFQDITSVVAMAKTYATTEAFIDSKYDIRIQKIGS
  NYKAYMRTSISGNWKANTGSAMLEQVAMTERYRLWVDSCSEMFGGLDICAVKAVHSKDGR
  DYIIEVMDSSMPLIGEHVEEDRQLMADLVVSKMSQLPMPGGTAPSPLRPWAPQIKSAKSP
  GQAQLGPQLGQPQPRPPPQGGPRQAQSPQPQRSGSPSQQRLSPQGQQPLSPQSGSPQQQR
  SPGSPQLSRASSGSSPNQASKPGATLASQPRPPVQGRSTSQQGEESKKPAPPHPHLNKSQ
  SLTNSLSTSDTSQRGTPSEDEAKAETIRNLRKSFASLFSD
• Function: May be involved in the regulation of neurotransmitter release and synaptogenesis.
• Tissue Specificity: Neuron specific. Detected predominantly in brain.
• Reactome Pathway:
  Dopamine Neurotransmitter Release Cycle (R-HSA-212676)
  Serotonin Neurotransmitter Release Cycle (R-HSA-181429)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Genetic Variation	[1]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[2]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[3]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[4]
Familial focal epilepsy with variable foci	DIS50BKW	Strong	Biomarker	[5]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[6]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[2]
Benign prostatic hyperplasia	DISI3CW2	moderate	Genetic Variation	[7]
Anxiety	DISIJDBA	Limited	Genetic Variation	[8]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[8]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[9]
Neoplasm	DISZKGEW	Limited	Biomarker	[10]
Pyoderma gangrenosum	DIS8QVTT	Limited	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Synapsin-3 (SYN3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Synapsin-3 (SYN3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Synapsin-3 (SYN3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Synapsin-3 (SYN3).	[12]

References

• [1] Synapsin III deficiency hampers -synuclein aggregation, striatal synaptic damage and nigral cell loss in an AAV-based mouse model of Parkinson's disease.Acta Neuropathol. 2018 Oct;136(4):621-639. doi: 10.1007/s00401-018-1892-1. Epub 2018 Jul 25.
• [2] A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.Nat Genet. 2016 Feb;48(2):134-43. doi: 10.1038/ng.3448. Epub 2015 Dec 21.
• [3] Analysis of synapsin III-196 promoter mutation in schizophrenia and bipolar disorder.Neuropsychobiology. 2006;53(2):57-62. doi: 10.1159/000091720. Epub 2006 Feb 23.
• [4] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [5] Predicting disease genes using protein-protein interactions.J Med Genet. 2006 Aug;43(8):691-8. doi: 10.1136/jmg.2006.041376. Epub 2006 Apr 12.
• [6] Association between synapsin III gene promoter SNPs and multiple sclerosis in Basque patients.Mult Scler. 2009 Jan;15(1):124-8. doi: 10.1177/1352458508096682. Epub 2008 Aug 28.
• [7] Heritability and genome-wide association study of benign prostatic hyperplasia (BPH) in the eMERGE network.Sci Rep. 2019 Apr 15;9(1):6077. doi: 10.1038/s41598-019-42427-z.
• [8] A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans.Transl Psychiatry. 2017 Dec 11;7(12):1282. doi: 10.1038/s41398-017-0047-9.
• [9] Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients.Inflamm Bowel Dis. 2014 Mar;20(3):525-33. doi: 10.1097/01.MIB.0000442011.60285.68.
• [10] Efficacy of a single intravesical treatment with Ad-IFN/Syn 3 is dependent on dose and urine IFN concentration obtained: implications for clinical investigation.Cancer Gene Ther. 2006 Feb;13(2):125-30. doi: 10.1038/sj.cgt.7700865.
• [11] 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.
• [12] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [13] 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.
• [14] 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.