Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTELSEK6)

DOT Name	Beta-synuclein (SNCB)
Gene Name	SNCB
Related Disease	Medulloblastoma ( ) Advanced cancer ( ) Autism ( ) Autism spectrum disorder ( ) Autonomic nervous system disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Cervical cancer ( ) Cervical carcinoma ( ) Dysautonomia ( ) Huntington disease ( ) Mitochondrial DNA depletion syndrome 4a ( ) Multiple sclerosis ( ) Obstructive sleep apnea ( ) Parkinsonian disorder ( ) Pervasive developmental disorder ( ) Prion disease ( ) Schizophrenia ( ) Uveitis ( ) Alzheimer disease ( ) Encephalitis ( ) Lewy body dementia ( ) Neuroblastoma ( ) Colorectal carcinoma ( ) Dementia ( ) Lafora disease ( ) Movement disorder ( ) Neoplasm ( ) Nervous system inflammation ( ) Sandhoff disease ( ) Young-onset Parkinson disease ( )
UniProt ID	SYUB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01387
Sequence	MDVFMKGLSMAKEGVVAAAEKTKQGVTEAAEKTKEGVLYVGSKTREGVVQGVASVAEKTK EQASHLGGAVFSGAGNIAAATGLVKREEFPTDLKPEEVAQEAAEEPLIEPLMEPEGESYE DPPQEEYQEYEPEA
Function	Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated caspase activation in a p53/TP53-dependent manner. Contributes to restore the SNCA anti-apoptotic function abolished by 6OHDA. Not found in the Lewy bodies associated with Parkinson disease.
Tissue Specificity	Expressed predominantly in brain; concentrated in presynaptic nerve terminals.
Reactome Pathway	MTF1 activates gene expression (R-HSA-5660489 )

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Medulloblastoma	DISZD2ZL	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Altered Expression	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Autonomic nervous system disorder	DIS6JLTA	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[2]
Dysautonomia	DISF4MT6	Strong	Biomarker	[4]
Huntington disease	DISQPLA4	Strong	Biomarker	[6]
Mitochondrial DNA depletion syndrome 4a	DISU4RVU	Strong	Biomarker	[7]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[8]
Obstructive sleep apnea	DIS0SVD1	Strong	Altered Expression	[9]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[10]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[3]
Prion disease	DISOUMB0	Strong	Biomarker	[11]
Schizophrenia	DISSRV2N	Strong	Biomarker	[12]
Uveitis	DISV0RYS	Strong	Biomarker	[13]
Alzheimer disease	DISF8S70	moderate	Genetic Variation	[14]
Encephalitis	DISLD1RL	moderate	Biomarker	[15]
Lewy body dementia	DISAE66J	Moderate	Unknown	[16]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[17]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[18]
Dementia	DISXL1WY	Limited	Genetic Variation	[14]
Lafora disease	DIS83JHH	Limited	Altered Expression	[19]
Movement disorder	DISOJJ2D	Limited	Biomarker	[14]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[20]
Sandhoff disease	DISELKA4	Limited	Biomarker	[21]
Young-onset Parkinson disease	DIS05LFS	Limited	Altered Expression	[22]
------------------------------------------------------------------------------------


⏷ Show the Full List of 31 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Beta-synuclein (SNCB).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Beta-synuclein (SNCB).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Beta-synuclein (SNCB).	[25]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Beta-synuclein (SNCB).	[27]
------------------------------------------------------------------------------------

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 Beta-synuclein (SNCB).	[26]
------------------------------------------------------------------------------------

References

1	Expression of alpha-, beta-, and gamma-synuclein in glial tumors and medulloblastomas.Acta Neuropathol. 2003 Aug;106(2):167-75. doi: 10.1007/s00401-003-0718-x. Epub 2003 May 28.
2	Silencing of Synuclein- inhibits human cervical cancer through the AKT signaling pathway.Cell Mol Biol Lett. 2019 Jul 10;24:49. doi: 10.1186/s11658-019-0172-y. eCollection 2019.
3	Significant Changes in Plasma Alpha-Synuclein and Beta-Synuclein Levels in Male Children with Autism Spectrum Disorder.Biomed Res Int. 2018 Apr 8;2018:4503871. doi: 10.1155/2018/4503871. eCollection 2018.
4	REM sleep behavior disorder, autonomic dysfunction and synuclein-related neurodegeneration: where do we stand?.Clin Auton Res. 2018 Dec;28(6):519-533. doi: 10.1007/s10286-017-0460-4. Epub 2017 Sep 4.
5	Gamma-synuclein: cell-type-specific promoter activity and binding to transcription factors.J Mol Neurosci. 2008 Jul;35(3):267-71. doi: 10.1007/s12031-008-9074-6. Epub 2008 May 23.
6	The therapeutic potential of intrabodies in neurologic disorders: focus on Huntington and Parkinson diseases.BioDrugs. 2006;20(6):327-33. doi: 10.2165/00063030-200620060-00002.
7	-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration.Nature. 2019 Feb;566(7745):503-508. doi: 10.1038/s41586-019-0964-2. Epub 2019 Feb 20.
8	HLA DR2b-binding peptides from human endogenous retrovirus envelope, Epstein-Barr virus and brain proteins in the context of molecular mimicry in multiple sclerosis.Immunol Lett. 2020 Jan;217:15-24. doi: 10.1016/j.imlet.2019.10.017. Epub 2019 Nov 3.
9	Plasma -synuclein levels are increased in patients with obstructive sleep apnea syndrome.Ann Clin Transl Neurol. 2019 Mar 12;6(4):788-794. doi: 10.1002/acn3.756. eCollection 2019 Apr.
10	Interface between tauopathies and synucleinopathies: a tale of two proteins.Ann Neurol. 2006 Mar;59(3):449-58. doi: 10.1002/ana.20819.
11	The genetics of disorders with synuclein pathology and parkinsonism.Hum Mol Genet. 1999;8(10):1901-5. doi: 10.1093/hmg/8.10.1901.
12	Alpha- and beta-synucleins mRNA expression in lymphocytes of schizophrenia patients.Genet Test Mol Biomarkers. 2010 Oct;14(5):725-9. doi: 10.1089/gtmb.2010.0050. Epub 2010 Sep 20.
13	Autoimmune encephalomyelitis and uveitis induced by T cell immunity to self beta-synuclein.J Immunol. 2003 Jan 1;170(1):628-34. doi: 10.4049/jimmunol.170.1.628.
14	Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies.Genes (Basel). 2018 Jan 25;9(2):63. doi: 10.3390/genes9020063.
15	-synuclein at the "synapse" of encephalitis and neurodegeneration in multiple sclerosis?.Immunol Cell Biol. 2019 Jul;97(6):523-525. doi: 10.1111/imcb.12270. Epub 2019 Jun 12.
16	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.
17	Neurotoxic conversion of beta-synuclein: a novel approach to generate a transgenic mouse model of synucleinopathies?.J Neurol. 2009 Aug;256 Suppl 3:286-92. doi: 10.1007/s00415-009-5246-8.
18	Expression of alpha-, beta- and gamma-synuclein in colorectal cancer, and potential clinical significance in progression of the disease.Oncol Rep. 2010 Feb;23(2):429-36.
19	Accumulation of beta-synuclein in cortical neurons is associated with autophagy attenuation in the brains of dementia with Lewy body patients.Brain Res. 2018 Feb 15;1681:1-13. doi: 10.1016/j.brainres.2017.12.026. Epub 2017 Dec 24.
20	Autoimmune spread to myelin is associated with experimental autoimmune encephalomyelitis induced by a neuronal protein, beta-synuclein.J Neuroimmunol. 2009 Mar 31;208(1-2):19-29. doi: 10.1016/j.jneuroim.2008.12.009. Epub 2009 Feb 1.
21	Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses.Acta Neuropathol. 2007 Nov;114(5):481-9. doi: 10.1007/s00401-007-0264-z. Epub 2007 Jul 25.
22	Alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease.Mov Disord. 1999 May;14(3):417-22. doi: 10.1002/1531-8257(199905)14:3<417::aid-mds1005>3.0.co;2-x.
23	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
24	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
25	Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
26	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.
27	MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.