Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSW59X0)

• DOT Name: Syntaxin-1B (STX1B)
• Synonyms: Syntaxin-1B1; Syntaxin-1B2
• Gene Name: STX1B
• Related Disease:
  Epilepsy syndrome
  Episodic kinesigenic dyskinesia
  Episodic kinesigenic dyskinesia 1
  Generalized epilepsy with febrile seizures plus
  Alzheimer disease
  Asthma
  Generalized epilepsy with febrile seizures plus, type 9
  Lafora disease
  Parkinson disease
  Movement disorder
  Epilepsy
  Myoclonic-astatic epilepsy
  Psoriasis
• UniProt ID: STX1B_HUMAN
• Pfam ID: PF05739 ; PF00804
• Sequence:
  MKDRTQELRSAKDSDDEEEVVHVDRDHFMDEFFEQVEEIRGCIEKLSEDVEQVKKQHSAI
  LAAPNPDEKTKQELEDLTADIKKTANKVRSKLKAIEQSIEQEEGLNRSSADLRIRKTQHS
  TLSRKFVEVMTEYNATQSKYRDRCKDRIQRQLEITGRTTTNEELEDMLESGKLAIFTDDI
  KMDSQMTKQALNEIETRHNEIIKLETSIRELHDMFVDMAMLVESQGEMIDRIEYNVEHSV
  DYVERAVSDTKKAVKYQSKARRKKIMIIICCVVLGVVLASSIGGTLGL
• Function: Potentially involved in docking of synaptic vesicles at presynaptic active zones. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Sy.ptic vesicle cycle (hsa04721)
• Reactome Pathway:
  LGI-ADAM interactions (R-HSA-5682910)
  Toxicity of botulinum toxin type C (botC) (R-HSA-5250971)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy syndrome	DISLYXJ3	Definitive	Genetic Variation	[1]
Episodic kinesigenic dyskinesia	DIS65CHB	Definitive	Biomarker	[2]
Episodic kinesigenic dyskinesia 1	DISGVQMP	Definitive	Biomarker	[2]
Generalized epilepsy with febrile seizures plus	DISJE0UU	Definitive	Autosomal dominant	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Biomarker	[4]
Generalized epilepsy with febrile seizures plus, type 9	DISTVY3H	Strong	Autosomal dominant	[5]
Lafora disease	DIS83JHH	Strong	Genetic Variation	[6]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[7]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[8]
Epilepsy	DISBB28L	Limited	Genetic Variation	[1]
Myoclonic-astatic epilepsy	DISTAVMU	Limited	Genetic Variation	[9]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[10]

5 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 Syntaxin-1B (STX1B).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntaxin-1B (STX1B).	[12]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Syntaxin-1B (STX1B).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Syntaxin-1B (STX1B).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Syntaxin-1B (STX1B).	[15]

References

• [1] Sleep-related hypermotor epilepsy and peri-ictal hypotension in a patient with syntaxin-1B mutation.Epileptic Disord. 2018 Oct 1;20(5):413-417. doi: 10.1684/epd.2018.0996.
• [2] A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B.Epilepsia. 2018 Aug;59(8):1621-1630. doi: 10.1111/epi.14511. Epub 2018 Jul 15.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] An integrative functional genomics framework for effective identification of novel regulatory variants in genome-phenome studies.Genome Med. 2018 Jan 29;10(1):7. doi: 10.1186/s13073-018-0513-x.
• [5] Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nat Genet. 2014 Dec;46(12):1327-32. doi: 10.1038/ng.3130. Epub 2014 Nov 2.
• [6] Parkinson's disease susceptibility variants and severity of Lewy body pathology.Parkinsonism Relat Disord. 2017 Nov;44:79-84. doi: 10.1016/j.parkreldis.2017.09.009. Epub 2017 Sep 11.
• [7] Polymorphisms of ACMSD-TMEM163, MCCC1, and BCKDK-STX1B Are Not Associated with Parkinson's Disease in Taiwan.Parkinsons Dis. 2019 Jan 2;2019:3489638. doi: 10.1155/2019/3489638. eCollection 2019.
• [8] Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.Mol Syndromol. 2016 Sep;7(4):210-219. doi: 10.1159/000448369. Epub 2016 Aug 20.
• [9] Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy.Eur J Paediatr Neurol. 2016 May;20(3):489-92. doi: 10.1016/j.ejpn.2015.12.014. Epub 2016 Jan 8.
• [10] Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.Nat Commun. 2015 Apr 23;6:6916. doi: 10.1038/ncomms7916.
• [11] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.