Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMNPWC1)

DOT Name	Synapsin-1 (SYN1)
Synonyms	Brain protein 4.1; Synapsin I
Gene Name	SYN1
Related Disease	Epilepsy ( ) Subarachnoid hemorrhage ( ) X-linked complex neurodevelopmental disorder ( ) X-linked intellectual disability ( ) Advanced cancer ( ) Alzheimer disease ( ) Amyloidosis ( ) Autism ( ) Cardiac arrest ( ) Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders ( ) Fibrosarcoma ( ) Fragile X syndrome ( ) Frontotemporal dementia ( ) Huntington disease ( ) Immunodeficiency ( ) Malignant peripheral nerve sheath tumor ( ) Malignant soft tissue neoplasm ( ) Mental disorder ( ) Multiple sclerosis ( ) Myotonic dystrophy ( ) Nervous system inflammation ( ) Rett syndrome ( ) Sarcoma ( ) Specific language impairment ( ) Vascular dementia ( ) Autism spectrum disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Epilepsy with generalized tonic-clonic seizures ( ) GM2 gangliosidosis ( ) Melanoma ( ) Schizophrenia ( ) Focal epilepsy ( ) Intellectual disability ( ) Pervasive developmental disorder ( ) Toxic shock syndrome ( ) Neuroblastoma ( )
UniProt ID	SYN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF02078 ; PF02750 ; PF10581
Sequence	MNYLRRRLSDSNFMANLPNGYMTDLQRPQPPPPPPGAHSPGATPGPGTATAERSSGVAPA ASPAAPSPGSSGGGGFFSSLSNAVKQTTAAAAATFSEQVGGGSGGAGRGGAASRVLLVID EPHTDWAKYFKGKKIHGEIDIKVEQAEFSDLNLVAHANGGFSVDMEVLRNGVKVVRSLKP DFVLIRQHAFSMARNGDYRSLVIGLQYAGIPSVNSLHSVYNFCDKPWVFAQMVRLHKKLG TEEFPLIDQTFYPNHKEMLSSTTYPVVVKMGHAHSGMGKVKVDNQHDFQDIASVVALTKT YATAEPFIDAKYDVRVQKIGQNYKAYMRTSVSGNWKTNTGSAMLEQIAMSDRYKLWVDTC SEIFGGLDICAVEALHGKDGRDHIIEVVGSSMPLIGDHQDEDKQLIVELVVNKMAQALPR QRQRDASPGRGSHGQTPSPGALPLGRQTSQQPAGPPAQQRPPPQGGPPQPGPGPQRQGPP LQQRPPPQGQQHLSGLGPPAGSPLPQRLPSPTSAPQQPASQAAPPTQGQGRQSRPVAGGP GAPPAARPPASPSPQRQAGPPQATRQTSVSGPAPPKASGAPPGGQQRQGPPQKPPGPAGP TRQASQAGPVPRTGPPTTQQPRPSGPGPAGRPKPQLAQKPSQDVPPPATAAAGGPPHPQL NKSQSLTNAFNLPEPAPPRPSLSQDEVKAETIRSLRKSFASLFSD
Function	Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal. Also involved in the regulation of axon outgrowth and synaptogenesis. The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level.
Reactome Pathway	Dopamine Neurotransmitter Release Cycle (R-HSA-212676 ) Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360 ) Serotonin Neurotransmitter Release Cycle (R-HSA-181429 )

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Epilepsy	DISBB28L	Definitive	Biomarker	[1]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Biomarker	[2]
X-linked complex neurodevelopmental disorder	DISI3QE9	Definitive	X-linked	[3]
X-linked intellectual disability	DISYJBY3	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Amyloidosis	DISHTAI2	Strong	Biomarker	[7]
Autism	DISV4V1Z	Strong	Genetic Variation	[8]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[9]
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders	DIS91ZQD	Strong	X-linked recessive	[10]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[11]
Fragile X syndrome	DISE8W3A	Strong	Altered Expression	[12]
Frontotemporal dementia	DISKYHXL	Strong	Biomarker	[13]
Huntington disease	DISQPLA4	Strong	Biomarker	[14]
Immunodeficiency	DIS093I0	Strong	Biomarker	[15]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[11]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[11]
Mental disorder	DIS3J5R8	Strong	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[17]
Myotonic dystrophy	DISNBEMX	Strong	Altered Expression	[18]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[17]
Rett syndrome	DISGG5UV	Strong	Biomarker	[19]
Sarcoma	DISZDG3U	Strong	Biomarker	[11]
Specific language impairment	DISEKRML	Strong	Genetic Variation	[20]
Vascular dementia	DISVO82H	Strong	Biomarker	[21]
Autism spectrum disorder	DISXK8NV	moderate	Biomarker	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[22]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[22]
Epilepsy with generalized tonic-clonic seizures	DISMG0FL	moderate	Biomarker	[23]
GM2 gangliosidosis	DISPT716	moderate	Biomarker	[24]
Melanoma	DIS1RRCY	moderate	Altered Expression	[25]
Schizophrenia	DISSRV2N	moderate	Biomarker	[26]
Focal epilepsy	DIS4LY5L	Disputed	Genetic Variation	[20]
Intellectual disability	DISMBNXP	Disputed	Genetic Variation	[8]
Pervasive developmental disorder	DIS51975	Disputed	Genetic Variation	[20]
Toxic shock syndrome	DISX5S53	Disputed	Altered Expression	[27]
Neuroblastoma	DISVZBI4	Limited	Posttranslational Modification	[28]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Synapsin-1 (SYN1).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Synapsin-1 (SYN1).	[32]
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4 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 Synapsin-1 (SYN1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synapsin-1 (SYN1).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Synapsin-1 (SYN1).	[33]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Synapsin-1 (SYN1).	[34]
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References

1	The Knockout of Synapsin II in Mice Impairs Social Behavior and Functional Connectivity Generating an ASD-like Phenotype.Cereb Cortex. 2017 Oct 1;27(10):5014-5023. doi: 10.1093/cercor/bhx207.
2	Protective effects of astaxanthin on subarachnoid hemorrhage-induced early brain injury: Reduction of cerebral vasospasm and improvement of neuron survival and mitochondrial function.Acta Histochem. 2019 Jan;121(1):56-63. doi: 10.1016/j.acthis.2018.10.014. Epub 2018 Nov 2.
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	Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).Am J Med Genet. 1997 Dec 31;73(4):474-9.
5	Expression profiling of RE1-silencing transcription factor (REST), REST corepressor 1 (RCOR1), and Synapsin 1 (SYN1) genes in human gliomas.J BUON. 2016 Jul-Aug;21(4):964-972.
6	Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer's disease mouse models.Behav Brain Res. 2017 Mar 30;322(Pt B):288-298. doi: 10.1016/j.bbr.2016.06.002. Epub 2016 Jun 2.
7	Synapsin 1 promotes A generation via BACE1 modulation.PLoS One. 2019 Dec 12;14(12):e0226368. doi: 10.1371/journal.pone.0226368. eCollection 2019.
8	A novel SYN1 missense mutation in non-syndromic X-linked intellectual disability affects synaptic vesicle life cycle, clustering and mobility.Hum Mol Genet. 2017 Dec 1;26(23):4699-4714. doi: 10.1093/hmg/ddx352.
9	Generation of a neurodegenerative disease mouse model using lentiviral vectors carrying an enhanced synapsin I promoter.J Neurosci Methods. 2014 Feb 15;223:133-43. doi: 10.1016/j.jneumeth.2013.12.004. Epub 2013 Dec 19.
10	Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
11	Purification and characterization of human lung fibroblast motility-stimulating factor for human soft tissue sarcoma cells: identification as an NH2-terminal fragment of human fibronectin.Cancer Res. 1997 Aug 15;57(16):3577-84.
12	Blocking elevated VEGF-A attenuates non-vasculature Fragile X syndrome abnormalities.Dev Neurobiol. 2017 Jan;77(1):14-25. doi: 10.1002/dneu.22404. Epub 2016 Jun 10.
13	Neurons and their dendrites in frontotemporal dementia.Dement Geriatr Cogn Disord. 1999;10 Suppl 1:55-60. doi: 10.1159/000051214.
14	Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes neurological symptoms.J Cell Biol. 2013 Sep 30;202(7):1123-38. doi: 10.1083/jcb.201303146.
15	SIV-Mediated Synaptic Dysfunction Is Associated with an Increase in Synapsin Site 1 Phosphorylation and Impaired PP2A Activity.J Neurosci. 2019 Aug 28;39(35):7006-7018. doi: 10.1523/JNEUROSCI.0178-19.2019. Epub 2019 Jul 3.
16	Subtle Phenotype Differences in Psychiatric Patients With and Without Serum Immunoglobulin G Antibodies to Synapsin.Front Psychiatry. 2019 Jun 7;10:401. doi: 10.3389/fpsyt.2019.00401. eCollection 2019.
17	Synapsin I deletion reduces neuronal damage and ameliorates clinical progression of experimental autoimmune encephalomyelitis.Brain Behav Immun. 2018 Feb;68:197-210. doi: 10.1016/j.bbi.2017.10.018. Epub 2017 Oct 21.
18	Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour.Brain. 2013 Mar;136(Pt 3):957-70. doi: 10.1093/brain/aws367. Epub 2013 Feb 11.
19	Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome.Neuromolecular Med. 2016 Sep;18(3):364-77. doi: 10.1007/s12017-016-8421-y. Epub 2016 Jul 5.
20	X-linked focal epilepsy with reflex bathing seizures: Characterization of a distinct epileptic syndrome.Epilepsia. 2015 Jul;56(7):1098-108. doi: 10.1111/epi.13042. Epub 2015 Jun 19.
21	miR?34?p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model.Int J Mol Med. 2019 Nov;44(5):1729-1740. doi: 10.3892/ijmm.2019.4331. Epub 2019 Sep 5.
22	Heparan sulfate mediates trastuzumab effect in breast cancer cells.BMC Cancer. 2013 Oct 1;13:444. doi: 10.1186/1471-2407-13-444.
23	Impaired GABA(B)-mediated presynaptic inhibition increases excitatory strength and alters short-term plasticity in synapsin knockout mice.Oncotarget. 2017 Sep 30;8(52):90061-90076. doi: 10.18632/oncotarget.21405. eCollection 2017 Oct 27.
24	Characterization of inducible models of Tay-Sachs and related disease.PLoS Genet. 2012 Sep;8(9):e1002943. doi: 10.1371/journal.pgen.1002943. Epub 2012 Sep 20.
25	MicroRNA-143 targets Syndecan-1 to repress cell growth in melanoma.PLoS One. 2014 Apr 10;9(4):e94855. doi: 10.1371/journal.pone.0094855. eCollection 2014.
26	The C allele of synonymous SNP (rs1142636, Asn170Asn) in SYN1 is a risk factor for the susceptibility of Korean female schizophrenia.Synapse. 2012 Nov;66(11):979-83. doi: 10.1002/syn.21583. Epub 2012 Aug 6.
27	Total Saikosaponins of Bupleurum yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice.BMC Complement Altern Med. 2018 Apr 2;18(1):117. doi: 10.1186/s12906-018-2186-9.
28	Schwann cells protect against CaMKII- and PKA-dependent Acrylamide-induced Synapsin I phosphorylation.Brain Res. 2018 Dec 15;1701:18-27. doi: 10.1016/j.brainres.2018.07.019. Epub 2018 Jul 17.
29	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.
30	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.
31	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.
32	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.
33	Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
34	High concentration of trichlorfon (1mM) disrupts axonal cytoskeleton and decreases the expression of plasticity-related proteins in SH-SY5Y cells. Toxicol In Vitro. 2017 Mar;39:84-92. doi: 10.1016/j.tiv.2016.12.003. Epub 2016 Dec 7.