SNCA (synuclein alpha)

Gene

• Entrez ID: 6622
• Gene name: Synuclein alpha
• Gene symbol: SNCA
• Synonyms: NACP, PARK1, PARK4, PD1
• Chromosome: 4
• Chromosome location: 4q22.1
• Summary: Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynapti

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104893875	C>T	Pathogenic	Missense variant, non coding transcript variant, genic upstream transcript variant, coding sequence variant
rs104893877	C>T	Pathogenic	Missense variant, non coding transcript variant, genic upstream transcript variant, coding sequence variant
rs144758871	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, genic upstream transcript variant, non coding transcript variant, coding sequence variant
rs201106962	A>C	Pathogenic, uncertain-significance	Coding sequence variant, genic upstream transcript variant, non coding transcript variant, missense variant
rs431905511	C>T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000032	hsa-miR-7-5p	qRT-PCR, Luciferase reporter assay, Western blot	19628698
MIRT000032	hsa-miR-7-5p	Luciferase reporter assay	19628698
MIRT000032	hsa-miR-7-5p	Immunocytochemistry, Luciferase reporter assay, qRT-PCR, Western blot	20106983
MIRT004733	hsa-miR-153-3p	Immunocytochemistry, Luciferase reporter assay, qRT-PCR, Western blot	20106983
MIRT054335	mmu-miR-153-3p	Luciferase reporter assay, qRT-PCR, Western blot	23595248
MIRT1375401	hsa-miR-1279	CLIP-seq
MIRT1375402	hsa-miR-3074-5p	CLIP-seq
MIRT1375403	hsa-miR-3607-3p	CLIP-seq
MIRT1375404	hsa-miR-3910	CLIP-seq
MIRT1375405	hsa-miR-3915	CLIP-seq
MIRT1375406	hsa-miR-3928	CLIP-seq
MIRT1375407	hsa-miR-4261	CLIP-seq
MIRT1375408	hsa-miR-4447	CLIP-seq
MIRT1375409	hsa-miR-4472	CLIP-seq
MIRT1375410	hsa-miR-4481	CLIP-seq
MIRT1375411	hsa-miR-4484	CLIP-seq
MIRT1375412	hsa-miR-4488	CLIP-seq
MIRT1375413	hsa-miR-4496	CLIP-seq
MIRT1375414	hsa-miR-4663	CLIP-seq
MIRT1375415	hsa-miR-4697-5p	CLIP-seq
MIRT1375416	hsa-miR-4728-3p	CLIP-seq
MIRT1375417	hsa-miR-4736	CLIP-seq
MIRT1375418	hsa-miR-4745-5p	CLIP-seq
MIRT1375419	hsa-miR-4758-5p	CLIP-seq
MIRT1375420	hsa-miR-486-3p	CLIP-seq
MIRT1375421	hsa-miR-486-5p	CLIP-seq
MIRT1375422	hsa-miR-494	CLIP-seq
MIRT1375423	hsa-miR-548an	CLIP-seq
MIRT2334796	hsa-miR-3614-5p	CLIP-seq
MIRT2334797	hsa-miR-421	CLIP-seq
MIRT2334798	hsa-miR-4286	CLIP-seq
MIRT2334799	hsa-miR-4691-5p	CLIP-seq
MIRT2691601	hsa-miR-1236	CLIP-seq
MIRT2691602	hsa-miR-1244	CLIP-seq
MIRT2691603	hsa-miR-1301	CLIP-seq
MIRT2691604	hsa-miR-3137	CLIP-seq
MIRT2691605	hsa-miR-3664-5p	CLIP-seq
MIRT2691606	hsa-miR-4474-5p	CLIP-seq
MIRT2691607	hsa-miR-4643	CLIP-seq
MIRT2691608	hsa-miR-4660	CLIP-seq
MIRT2691609	hsa-miR-5047	CLIP-seq
MIRT2691610	hsa-miR-642b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	TAS	24252804
GO:0000149	Function	SNARE binding	IDA	20798282
GO:0000287	Function	Magnesium ion binding	IDA	11850416
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	TAS	24252804
GO:0001774	Process	Microglial cell activation	TAS	24252804
GO:0001921	Process	Positive regulation of receptor recycling	IDA	18980610
GO:0003779	Function	Actin binding	IPI	18331289
GO:0004860	Function	Protein kinase inhibitor activity	TAS	30194957
GO:0005504	Function	Fatty acid binding	IDA	16687662
GO:0005507	Function	Copper ion binding	IDA	21319811, 21320589
GO:0005509	Function	Calcium ion binding	IDA	11312271, 11850416
GO:0005515	Function	Protein binding	IPI	10319874, 11943812, 11956199, 12044636, 12059041, 12958153, 15207266, 15590652, 15671022, 16595633, 16882008, 17027006, 17156375, 18331289, 19549071, 19762560, 20798282, 21320589, 21798244, 21985244, 22119730, 22163275, 22854022, 23183827, 24412932, 24895406, 25241761, 26921451, 276
GO:0005543	Function	Phospholipid binding	IDA	17222866
GO:0005576	Component	Extracellular region	IDA	15863497
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	24936070
GO:0005634	Component	Nucleus	IDA	12406186, 16959795, 17408955, 24936070
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	12406186, 12958153, 15863497, 16959795, 17408955, 23983262, 24403142, 25561023
GO:0005739	Component	Mitochondrion	TAS	24252804
GO:0005764	Component	Lysosome	TAS	24477431
GO:0005829	Component	Cytosol	IDA	8248242, 24936070, 31034892
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	12958153, 15641770, 17222866
GO:0005938	Component	Cell cortex	IDA	19157893
GO:0006469	Process	Negative regulation of protein kinase activity	TAS	30194957
GO:0006915	Process	Apoptotic process	IEA
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	21050448
GO:0007268	Process	Chemical synaptic transmission	IBA	21873635
GO:0008198	Function	Ferrous iron binding	IDA	11850416
GO:0008270	Function	Zinc ion binding	IDA	11850416
GO:0010040	Process	Response to iron(II) ion	IDA	11850416
GO:0010517	Process	Regulation of phospholipase activity	IDA	15641770
GO:0010642	Process	Negative regulation of platelet-derived growth factor receptor signaling pathway	IDA	12239163
GO:0014059	Process	Regulation of dopamine secretion	TAS	21320589
GO:0015629	Component	Actin cytoskeleton	IDA	17408955
GO:0016020	Component	Membrane	IDA	24936070
GO:0016079	Process	Synaptic vesicle exocytosis	IDA	28288128
GO:0016082	Process	Synaptic vesicle priming	IMP	30404828
GO:0016234	Component	Inclusion body	IDA	17222866, 20039155
GO:0016491	Function	Oxidoreductase activity	IDA	21320589
GO:0019894	Function	Kinesin binding	IPI	16176937
GO:0022898	Process	Regulation of transmembrane transporter activity	IGI	18331289
GO:0030424	Component	Axon	IDA	12958153
GO:0030426	Component	Growth cone	IDA	12958153
GO:0030544	Function	Hsp70 protein binding	IPI	18975920
GO:0031092	Component	Platelet alpha granule membrane	IDA	12239163
GO:0031115	Process	Negative regulation of microtubule polymerization	IDA	21127069
GO:0031623	Process	Receptor internalization	IDA	18980610
GO:0031648	Process	Protein destabilization	IDA	21320589
GO:0032026	Process	Response to magnesium ion	IDA	11850416
GO:0032410	Process	Negative regulation of transporter activity	IDA	16882008
GO:0032496	Process	Response to lipopolysaccharide	IDA	12406186
GO:0032769	Process	Negative regulation of monooxygenase activity	IDA	11943812
GO:0032991	Component	Protein-containing complex	IMP	31034892
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	ISS
GO:0034341	Process	Response to interferon-gamma	IDA	19157893
GO:0034599	Process	Cellular response to oxidative stress	IC	23507046
GO:0035067	Process	Negative regulation of histone acetylation	IDA	16959795
GO:0035493	Process	SNARE complex assembly	IDA	20798282
GO:0035543	Process	Positive regulation of SNARE complex assembly	IDA	20798282
GO:0042393	Function	Histone binding	IDA	16959795
GO:0042416	Process	Dopamine biosynthetic process	TAS	21320589
GO:0042802	Function	Identical protein binding	IDA	24936070, 25561023
GO:0042802	Function	Identical protein binding	IPI	15502874, 16330551, 16764865, 18614564, 19745811, 19875982, 21443877, 22119730, 22854022, 23927048, 24374342, 24895406, 24983211, 25643172, 25732184, 31270237, 32461689
GO:0043014	Function	Alpha-tubulin binding	IPI	11698390
GO:0043025	Component	Neuronal cell body	IBA	21873635
GO:0043027	Function	Cysteine-type endopeptidase inhibitor activity involved in apoptotic process	IDA	10818098
GO:0043065	Process	Positive regulation of apoptotic process	TAS	24252804
GO:0043066	Process	Negative regulation of apoptotic process	IMP	10818098
GO:0043154	Process	Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	10818098
GO:0043679	Component	Axon terminus	IBA	21873635
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045807	Process	Positive regulation of endocytosis	IDA	18980610
GO:0045920	Process	Negative regulation of exocytosis	IMP	12239163
GO:0045921	Process	Positive regulation of exocytosis	IMP	30404828
GO:0048156	Function	Tau protein binding	IDA	17408955, 21127069
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	20039155
GO:0048488	Process	Synaptic vesicle endocytosis	IBA	21873635
GO:0048488	Process	Synaptic vesicle endocytosis	ISS
GO:0050729	Process	Positive regulation of inflammatory response	IDA	25533483
GO:0050808	Process	Synapse organization	IBA	21873635
GO:0051219	Function	Phosphoprotein binding	IDA	21127069
GO:0051262	Process	Protein tetramerization	IDA	21841800
GO:0051281	Process	Positive regulation of release of sequestered calcium ion into cytosol	IDA	15641770
GO:0051583	Process	Dopamine uptake involved in synaptic transmission	TAS	21320589
GO:0051585	Process	Negative regulation of dopamine uptake involved in synaptic transmission	IDA	12958153
GO:0051612	Process	Negative regulation of serotonin uptake	IDA	16882008
GO:0051621	Process	Regulation of norepinephrine uptake	IGI	18331289
GO:0051622	Process	Negative regulation of norepinephrine uptake	IDA	17156375
GO:0055074	Process	Calcium ion homeostasis	IDA	12239163
GO:0060732	Process	Positive regulation of inositol phosphate biosynthetic process	IDA	15641770
GO:0060961	Function	Phospholipase D inhibitor activity	IDA	19146388
GO:0070495	Process	Negative regulation of thrombin-activated receptor signaling pathway	IDA	12239163
GO:0070555	Process	Response to interleukin-1	IDA	12406186
GO:0070840	Function	Dynein complex binding	IPI	16176937
GO:0071280	Process	Cellular response to copper ion	IDA	21320589
GO:0071872	Process	Cellular response to epinephrine stimulus	TAS	21320589
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	21127069
GO:0097435	Process	Supramolecular fiber organization	TAS	21320589
GO:0099512	Component	Supramolecular fiber	IDA	17222866, 18346205, 23507046
GO:1901214	Process	Regulation of neuron death	IBA	21873635
GO:1901215	Process	Negative regulation of neuron death	IDA	15863497
GO:1901216	Process	Positive regulation of neuron death	IDA	25533483
GO:1902957	Process	Negative regulation of mitochondrial electron transport, NADH to ubiquinone	TAS	24252804
GO:1903136	Function	Cuprous ion binding	IBA	21873635
GO:1903136	Function	Cuprous ion binding	IMP	25495902
GO:1903284	Process	Positive regulation of glutathione peroxidase activity	IDA	23507046
GO:1903285	Process	Positive regulation of hydrogen peroxide catabolic process	IDA	23507046
GO:1903421	Process	Regulation of synaptic vesicle recycling	TAS	23983262
GO:1903426	Process	Regulation of reactive oxygen species biosynthetic process	TAS	24252804
GO:1904715	Process	Negative regulation of chaperone-mediated autophagy	IMP	20697033
GO:1905606	Process	Regulation of presynapse assembly	IGI	25533483

Other IDs

• MIM: 163890
• HGNC: 11138
• e!Ensembl: ENSG00000145335

Protein

• UniProt ID: P37840
• Protein name: Alpha-synuclein (Non-A beta component of AD amyloid) (Non-A4 component of amyloid precursor) (NACP)
• Protein function: Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:28288128, PubMed:30404828). Participates as a mon
• PDB: 1XQ8, 2JN5, 2KKW, 2M55, 2N0A, 2X6M, 3Q25, 3Q26, 3Q27, 3Q28, 3Q29, 4BXL, 4R0U, 4R0W, 4RIK, 4RIL, 4ZNN, 5CRW, 6A6B, 6CT7, 6CU7, 6CU8, 6H6B, 6I42, 6L1T, 6L1U, 6L4S, 6LRQ, 6OSJ, 6OSL, 6OSM, 6PEO, 6PES, 6RT0, 6RTB, 6SST, 6SSX, 6UFR, 6XYO, 6XYP, 6XYQ, 7C1D, 7E0F, 7L7H, 7LC9, 7NCA, 7NCG, 7NCH, 7NCI, 7NCJ, 7NCK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01387	Synuclein	1 → 131	Synuclein	Family

• Sequence:

  MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
  EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
  DNEAYEMPSEEGYQDYEPEA

• Sequence length: 140

Pathways

KEGG:

Alzheimer disease
Parkinson disease
Pathways of neurodegeneration - multiple diseases

Reactome:

Amyloid fiber formation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Akinesia	Akinesia	rs606231129, rs606231131, rs606231132, rs118203995, rs606231133, rs104894299, rs104894300, rs786200904, rs786200905, rs104894294, rs121909254, rs121909255, rs121909256, rs150376433, rs863223335, rs751889864, rs559933584, rs761899995, rs797045528, rs551423795, rs886037842, rs560525099, rs775583136, rs1349476281, rs794727884, rs1479498379, rs1555142142, rs1558010146, rs1558003446, rs1554757237, rs770987150, rs768892432, rs1558008455, rs1560224831, rs1558005340, rs747595523, rs1567568217, rs774070092, rs776532930, rs765096923, rs1560200925, rs201947904, rs1595903667, rs376573993, rs778172294, rs759488854, rs761584017, rs769850502
Dysautonomia	Dysautonomia	rs111033171, rs137853022, rs28939712, rs754348901, rs749052963, rs1057517169, rs1057516865, rs763445509, rs767527819, rs781333644, rs1239081703, rs1554696574, rs539544212, rs1201626345, rs774890086, rs1554703061, rs1554703613, rs1319053366, rs1554703851, rs868073099, rs926177767, rs376078668, rs1554695299, rs1554696648, rs1554696934, rs1554699327, rs1554691572, rs1554695846, rs1554697001, rs770668926, rs1554698037, rs759412460, rs1554702142, rs765572951, rs1554702880, rs1554703831, rs760774999, rs1554696650, rs757972943, rs1554703874, rs1554703907, rs571348995
Gaucher disease	Gaucher Disease, Gaucher Disease, Type 2 (disorder), Gaucher Disease, Type 3 (disorder), Gaucher Disease, Type 1	rs121908295, rs79653797, rs80356769, rs1064651, rs77369218, rs80356771, rs77829017, rs74500255, rs381737, rs387906315, rs121908310, rs121908298, rs76539814, rs397518433, rs121908299, rs75822236, rs121908302, rs364897, rs121908303, rs121908304, rs121908305, rs121908306, rs121908307, rs1141814, rs397518434, rs121908308, rs74598136, rs78198234, rs121908309, rs121908311, rs78973108, rs80356763, rs121908312, rs121908313, rs121908314, rs1571964338, rs121918105, rs121918106, rs121918108, rs121918109, rs121918110, rs80356772, rs1064644, rs439898, rs104886460, rs398123527, rs398123528, rs421016, rs398123530, rs398123532, rs61748906, rs381418, rs409652, rs80356768, rs794727908, rs747506979, rs878853317, rs878853320, rs878853315, rs878853321, rs878853314, rs1553217946, rs1553333346, rs1553217314, rs1553217879, rs1553217009, rs1553217294, rs1553216985, rs149171124, rs1553217626, rs772548282, rs1557901325, rs754743440, rs773409311, rs867929413, rs749714463, rs79796061, rs1237637353, rs761621516, rs1571969643, rs755265316, rs1571965880, rs765633380, rs1671890998	19576930
Parkinson disease	Parkinsonian Disorders, Autosomal Dominant Juvenile Parkinson Disease, PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE (disorder), PARKINSON DISEASE 4, AUTOSOMAL DOMINANT LEWY BODY (disorder), PARKINSON DISEASE 1, AUTOSOMAL DOMINANT (disorder), PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE, Parkinson Disease, Young-onset Parkinson disease	rs116074753, rs118203903, rs118203904, rs115735611, rs33939927, rs35801418, rs34805604, rs35870237, rs34995376, rs74315355, rs28940284, rs74315356, rs74315357, rs28940285, rs730880302, rs750664040, rs74315359, rs74315360, rs45539432, rs74315361, rs119451946, rs80356771, rs74500255, rs75822236, rs1141814, rs78973108, rs121908681, rs121908686, rs121908687, rs137853054, rs137853055, rs137853056, rs137853057, rs137853058, rs137853059, rs34424986, rs137853060, rs397518439, rs28938172, rs74315351, rs74315353, rs137853051, rs118192098, rs121917767, rs121918104, rs1589451049, rs104893877, rs104893878, rs283413, rs112176450, rs111290936, rs188286943, rs387906863, rs387906864, rs774631197, rs199935023, rs387906942, rs397514694, rs398122403, rs398122404, rs398122405, rs104886460, rs409652, rs431905511, rs63751392, rs756677845, rs864309527, rs864309650, rs750014782, rs1554391082, rs864622011, rs869312810, rs869312809, rs869312811, rs369100678, rs879253853, rs869320761, rs747506979, rs879255630, rs886039854, rs191486604, rs781442277, rs1060499619, rs751037529, rs55777503, rs768091663, rs34208370, rs1553122929, rs772786691, rs754809877, rs1555907463, rs1557561340, rs781600849, rs141263564, rs1557901552, rs777160388, rs756783990, rs867929413, rs1237637353, rs1005937012, rs755000580, rs747427602, rs1578089802, rs771586218, rs748142049, rs1582953433, rs746646126, rs771529549, rs121918106	23295396, 26558463, 26687234, 27324791, 27026137, 20464527, 22319455, 26075822, 23046578, 26687234, 26558463, 27324791, 22319455, 26075822, 23046578, 20464527, 23295396, 27026137, 23526723, 9197268, 14755719, 9462735, 23427326, 24936070, 23457019, 25561023, 23046578, 22319455, 26687234, 26558463, 23295396, 27324791, 20464527, 27026137, 26075822, 21738487, 12732244, 24511991, 20711177, 22355530, 18841091, 17690948, 18322262, 25149416, 25064009, 21044948, 19915576, 21245015, 12885775, 21084426, 21292315, 14535945, 20664293, 22110584, 17131421, 25475535, 20070850, 21892157, 25106480, 28011712, 24833599, 22438815, 22166454, 22451204, 30957308, 19915575, 25631236, 28892059, 11535288, 22185909, 22043175, 12151787, 15099020, 18353766, 27182965, 24509835
Parkinsonian-pyramidal syndrome	Parkinsonian-pyramidal syndrome	rs71799110, rs121918304, rs730880272, rs121918305, rs1228608709, rs1290655316, rs749534144, rs749019340
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313

Unknown
Disease name	Disease term	dbSNP ID	References
Abnormal male sexual function	Abnormal male sexual function
Anxiety disorder	Anxiety		29942085
Cerebral cortical atrophy	Cerebral cortical atrophy
Congenital clubfoot	Congenital clubfoot
Degenerative diseases, central nervous system	Degenerative Diseases, Central Nervous System, Degenerative Diseases, Spinal Cord		17296847, 22430071, 26075822, 18514411, 22430071, 18514411, 17296847, 26075822
Delusions	Delusions
Dementia	Dementia
Dementia of frontal lobe	Dementia of frontal lobe type
Dementia with lewy body	NON RARE IN EUROPE: Dementia with Lewy body
Dysarthria	Dysarthria
Dyskinetic syndrome	Dyskinetic syndrome
Dysphagia	Deglutition Disorders
Dyssomnia	Dyssomnias
Female sexual dysfunction	Female sexual dysfunction
Gastroparesis	Gastroparesis
Hallucinations	Hallucinations
Hepatolenticular degeneration	Hepatolenticular Degeneration, Hepatic Form of Wilson Disease		23519153
Hereditary parkinson`s disease	Hereditary late-onset Parkinson disease
Lewy body disease	Lewy Body Disease		16141792, 29263008, 19628769, 14755719
Male sexual dysfunction	Male sexual dysfunction
Mental depression	Depressive disorder	rs587778876, rs587778877
Neurodegenerative disorders	Neurodegenerative Disorders		26075822, 22430071, 17296847, 18514411
Neurogenic urinary bladder	Neurogenic Urinary Bladder
Panic disorder	Panic Attacks
Paranoia	Paranoia
Parkinsonian disease	Autosomal Dominant Parkinsonism, Autosomal Recessive Parkinsonism, Familial Juvenile Parkinsonism, Parkinsonism, Juvenile		23046578, 23295396, 26075822, 26558463, 26687234, 22319455, 20464527, 27026137, 27324791, 27026137, 23046578, 20464527, 26558463, 26687234, 23295396, 27324791, 26075822, 22319455, 27026137, 26558463, 26075822, 26687234, 20464527, 22319455, 27324791, 23046578, 23295396, 26687234, 27026137, 20464527, 27324791, 26558463, 22319455, 23295396, 23046578, 26075822
Ramsay hunt paralysis syndrome	Ramsay Hunt Paralysis Syndrome		26558463, 27324791, 20464527, 27026137, 26075822, 23295396, 23046578, 26687234, 22319455
Restless legs syndrome	Restless Legs Syndrome
Sleep disorders	Sleep Disorders
Social communication disorder	Social Communication Disorder