Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJYGTY4)

• DOT Name: Synaptotagmin-2 (SYT2)
• Synonyms: Synaptotagmin II; SytII
• Gene Name: SYT2
• Related Disease:
  LambertEaton myasthenic syndrome
  Attention deficit hyperactivity disorder
  Congenital myasthenic syndrome 7
  Epilepsy
  Mental disorder
  Acute myelogenous leukaemia
  Obsolete presynaptic congenital myasthenic syndrome
• UniProt ID: SYT2_HUMAN
• PDB ID: 6G5G
• Pfam ID: PF00168
• Sequence:
  MRNIFKRNQEPIVAPATTTATMPIGPVDNSTESGGAGESQEDMFAKLKEKLFNEINKIPL
  PPWALIAIAVVAGLLLLTCCFCICKKCCCKKKKNKKEKGKGMKNAMNMKDMKGGQDDDDA
  ETGLTEGEGEGEEEKEPENLGKLQFSLDYDFQANQLTVGVLQAAELPALDMGGTSDPYVK
  VFLLPDKKKKYETKVHRKTLNPAFNETFTFKVPYQELGGKTLVMAIYDFDRFSKHDIIGE
  VKVPMNTVDLGQPIEEWRDLQGGEKEEPEKLGDICTSLRYVPTAGKLTVCILEAKNLKKM
  DVGGLSDPYVKIHLMQNGKRLKKKKTTVKKKTLNPYFNESFSFEIPFEQIQKVQVVVTVL
  DYDKLGKNEAIGKIFVGSNATGTELRHWSDMLANPRRPIAQWHSLKPEEEVDALLGKNK
• Function: Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties. May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. Plays a role in dendrite formation by melanocytes.
• Tissue Specificity: Expressed at the neuromuscular junction . Expressed in melanocytes .
• Reactome Pathway:
  Neurexins and neuroligins (R-HSA-6794361)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Toxicity of botulinum toxin type B (botB) (R-HSA-5250958)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
LambertEaton myasthenic syndrome	DISN0Q7Q	Definitive	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Congenital myasthenic syndrome 7	DISEFB80	Strong	Autosomal dominant	[3]
Epilepsy	DISBB28L	Strong	Genetic Variation	[4]
Mental disorder	DIS3J5R8	Strong	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[6]
Obsolete presynaptic congenital myasthenic syndrome	DISCATK3	Supportive	Autosomal dominant	[1]

2 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 Synaptotagmin-2 (SYT2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Synaptotagmin-2 (SYT2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synaptotagmin-2 (SYT2).	[9]

References

• [1] Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014 Sep 4;95(3):332-9. doi: 10.1016/j.ajhg.2014.08.007.
• [2] Evaluation of common variants in 16 genes involved in the regulation of neurotransmitter release in ADHD.Eur Neuropsychopharmacol. 2013 Jun;23(6):426-35. doi: 10.1016/j.euroneuro.2012.07.014. Epub 2012 Aug 30.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] GWAS identifies two susceptibility loci for lamotrigine-induced skin rash in patients with epilepsy.Epilepsy Res. 2015 Sep;115:88-94. doi: 10.1016/j.eplepsyres.2015.05.014. Epub 2015 Jun 2.
• [5] SNARE complex in developmental psychiatry: neurotransmitter exocytosis and beyond.J Neural Transm (Vienna). 2016 Aug;123(8):867-83. doi: 10.1007/s00702-016-1514-9. Epub 2016 Feb 8.
• [6] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] 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.