Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRYA8C3)

• DOT Name: Syntaxin-binding protein 1 (STXBP1)
• Synonyms: MUNC18-1; N-Sec1; Protein unc-18 homolog 1; Unc18-1; Protein unc-18 homolog A; Unc-18A; p67
• Gene Name: STXBP1
• Related Disease:
  Amyotrophic lateral sclerosis
  Developmental and epileptic encephalopathy, 4
  Infantile spasm
  Pyridoxine-dependent epilepsy
  Alzheimer disease
  Autism
  Cerebellar ataxia
  CLN1 disease
  Cytochrome-c oxidase deficiency disease
  Developmental and epileptic encephalopathy, 21
  Dravet syndrome
  Early myoclonic encephalopathy
  Familial infantile myoclonic epilepsy
  Fragile X syndrome
  Lissencephaly spectrum disorders
  Mitochondrial complex I deficiency
  Myocardial infarction
  Myoclonic-astatic epilepsy
  Neurodevelopmental disorder
  Parkinson disease
  Parkinsonian disorder
  Rett syndrome, congenital variant
  Schizophrenia
  Type-1/2 diabetes
  Epilepsy syndrome
  Movement disorder
  Atypical Rett syndrome
  Autosomal dominant non-syndromic intellectual disability
  Obsolete Dravet syndrome
  Undetermined early-onset epileptic encephalopathy
  West syndrome
  Autism spectrum disorder
  Colorectal carcinoma
  Intellectual disability
  Megalencephaly
  Neoplasm
• UniProt ID: STXB1_HUMAN
• PDB ID: 6L03
• Pfam ID: PF00995
• Sequence:
  MAPIGLKAVVGEKIMHDVIKKVKKKGEWKVLVVDQLSMRMLSSCCKMTDIMTEGITIVED
  INKRREPLPSLEAVYLITPSEKSVHSLISDFKDPPTAKYRAAHVFFTDSCPDALFNELVK
  SRAAKVIKTLTEINIAFLPYESQVYSLDSADSFQSFYSPHKAQMKNPILERLAEQIATLC
  ATLKEYPAVRYRGEYKDNALLAQLIQDKLDAYKADDPTMGEGPDKARSQLLILDRGFDPS
  SPVLHELTFQAMSYDLLPIENDVYKYETSGIGEARVKEVLLDEDDDLWIALRHKHIAEVS
  QEVTRSLKDFSSSKRMNTGEKTTMRDLSQMLKKMPQYQKELSKYSTHLHLAEDCMKHYQG
  TVDKLCRVEQDLAMGTDAEGEKIKDPMRAIVPILLDANVSTYDKIRIILLYIFLKNGITE
  ENLNKLIQHAQIPPEDSEIITNMAHLGVPIVTDSTLRRRSKPERKERISEQTYQLSRWTP
  IIKDIMEDTIEDKLDTKHYPYISTRSSASFSTTAVSARYGHWHKNKAPGEYRSGPRLIIF
  ILGGVSLNEMRCAYEVTQANGKWEVLIGSTHILTPQKLLDTLKKLNKTDEEISS
• Function: Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins. Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. Involved in the release of neurotransmitters from neurons through interacting with SNARE complex component STX1A and mediating the assembly of the SNARE complex at synaptic membranes. May play a role in determining the specificity of intracellular fusion reactions.
• Tissue Specificity: Brain and spinal cord. Highly enriched in axons.
• KEGG Pathway: Sy.ptic vesicle cycle (hsa04721)
• Reactome Pathway:
  (Name not found)
  Neurexins and neuroligins (R-HSA-6794361)
  Regulation of insulin secretion (R-HSA-422356)

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Definitive	Biomarker	[1]
Developmental and epileptic encephalopathy, 4	DIS2XFG9	Definitive	Autosomal recessive	[2]
Infantile spasm	DISZSKDG	Definitive	Autosomal dominant	[3]
Pyridoxine-dependent epilepsy	DISVYADQ	Definitive	Genetic Variation	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Autism	DISV4V1Z	Strong	Genetic Variation	[6]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[7]
CLN1 disease	DISAIONI	Strong	Biomarker	[8]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Genetic Variation	[9]
Developmental and epileptic encephalopathy, 21	DISA3UBY	Strong	CausalMutation	[10]
Dravet syndrome	DISJF7LY	Strong	Genetic Variation	[11]
Early myoclonic encephalopathy	DIS1YXVQ	Strong	Genetic Variation	[12]
Familial infantile myoclonic epilepsy	DISELJ0F	Strong	Biomarker	[13]
Fragile X syndrome	DISE8W3A	Strong	Biomarker	[14]
Lissencephaly spectrum disorders	DISBCZL7	Strong	Genetic Variation	[15]
Mitochondrial complex I deficiency	DIS13M7V	Strong	Genetic Variation	[16]
Myocardial infarction	DIS655KI	Strong	Biomarker	[17]
Myoclonic-astatic epilepsy	DISTAVMU	Strong	Biomarker	[13]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[18]
Parkinson disease	DISQVHKL	Strong	Biomarker	[19]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[16]
Rett syndrome, congenital variant	DISQTBQI	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Biomarker	[21]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[22]
Epilepsy syndrome	DISLYXJ3	moderate	Genetic Variation	[23]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[10]
Atypical Rett syndrome	DISWF699	Supportive	Autosomal dominant	[24]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[10]
Obsolete Dravet syndrome	DISM4LMK	Supportive	Autosomal dominant	[25]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[10]
West syndrome	DISLIAU9	Supportive	Autosomal dominant	[26]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[2]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[27]
Intellectual disability	DISMBNXP	Limited	Autosomal dominant	[2]
Megalencephaly	DISYW5SV	Limited	Biomarker	[28]
Neoplasm	DISZKGEW	Limited	Altered Expression	[29]

13 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-binding protein 1 (STXBP1).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Syntaxin-binding protein 1 (STXBP1).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[33]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[34]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[35]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[36]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[37]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Syntaxin-binding protein 1 (STXBP1).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntaxin-binding protein 1 (STXBP1).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Syntaxin-binding protein 1 (STXBP1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Syntaxin-binding protein 1 (STXBP1).	[42]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Syntaxin-binding protein 1 (STXBP1).	[43]

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 Syntaxin-binding protein 1 (STXBP1).	[39]

References

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