SNCB

Summary

SNCB (synuclein beta, HGNC:11140) is a protein-coding gene on chromosome 5q35.2, encoding Beta-synuclein (Q16143). Non-amyloid component of senile plaques found in Alzheimer disease.

This gene encodes a member of a small family of proteins that inhibit phospholipase D2 and may function in neuronal plasticity. The encoded protein is abundant in lesions of patients with Alzheimer disease. A mutation in this gene was found in individuals with dementia with Lewy bodies. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6620 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lewy body dementia (Moderate, GenCC)
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_003085

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11140
Approved symbol	SNCB
Name	synuclein beta
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000074317
Ensembl biotype	protein_coding
OMIM	602569
Entrez	6620

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 27 protein_coding, 1 retained_intron

ENST00000310112, ENST00000393693, ENST00000506696, ENST00000508006, ENST00000510387, ENST00000614675, ENST00000862608, ENST00000862609, ENST00000862610, ENST00000862611, ENST00000862612, ENST00000862613, ENST00000912556, ENST00000912557, ENST00000912558, ENST00000912559, ENST00000946187, ENST00000946188, ENST00000946189, ENST00000946190, ENST00000946191, ENST00000946192, ENST00000946193, ENST00000946194, ENST00000946195, ENST00000946196, ENST00000946197, ENST00000946198

RefSeq mRNA: 7 — MANE Select: NM_003085 NM_001001502, NM_001318034, NM_001318035, NM_001318036, NM_001318037, NM_001363140, NM_003085

CCDS: CCDS4406, CCDS83048

Canonical transcript exons

ENST00000393693 — 6 exons

Exon	Start	End
ENSE00000770023	176626398	176626516
ENSE00000829006	176626720	176626761
ENSE00000829007	176629534	176629663
ENSE00001196517	176620082	176620843
ENSE00001366478	176630280	176630534
ENSE00003602811	176621214	176621303

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.44.

FANTOM5 (CAGE): breadth broad, TPM avg 11.4732 / max 775.0952, expressed in 391 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65050	7.1603	338
65049	3.0253	172
65051	0.7064	114
65048	0.2912	78
65047	0.1272	53
65045	0.0935	39
65046	0.0693	41

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.44	gold quality
right frontal lobe	UBERON:0002810	99.42	gold quality
cerebellar hemisphere	UBERON:0002245	99.33	gold quality
cerebellar cortex	UBERON:0002129	99.29	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.99	gold quality
anterior cingulate cortex	UBERON:0009835	98.95	gold quality
cingulate cortex	UBERON:0003027	98.91	gold quality
cerebellum	UBERON:0002037	98.57	gold quality
prefrontal cortex	UBERON:0000451	98.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.40	gold quality
paraflocculus	UBERON:0005351	98.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.15	gold quality
frontal pole	UBERON:0002795	97.89	gold quality
amygdala	UBERON:0001876	97.68	gold quality
frontal cortex	UBERON:0001870	97.67	gold quality
neocortex	UBERON:0001950	96.90	gold quality
cerebral cortex	UBERON:0000956	95.71	gold quality
telencephalon	UBERON:0001893	94.72	gold quality
hypothalamus	UBERON:0001898	94.66	gold quality
postcentral gyrus	UBERON:0002581	94.61	gold quality
orbitofrontal cortex	UBERON:0004167	94.39	gold quality
nucleus accumbens	UBERON:0001882	94.35	gold quality
superior frontal gyrus	UBERON:0002661	94.28	gold quality
caudate nucleus	UBERON:0001873	93.86	gold quality
temporal lobe	UBERON:0001871	93.85	gold quality
Ammon’s horn	UBERON:0001954	93.85	gold quality
parietal lobe	UBERON:0001872	93.74	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.68	gold quality
brain	UBERON:0000955	93.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.42	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	249.01
E-HCAD-35	yes	38.55
E-MTAB-5061	yes	15.69
E-MTAB-7316	yes	12.43
E-MTAB-7008	yes	7.80
E-ANND-3	no	2.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MTF1

miRNA regulators (miRDB)

47 targeting SNCB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-6795-5P	98.52	68.51	1277

Literature-anchored findings (GeneRIF, showing 40)

• Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins (PMID:11812782)
• Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-synuclein or both; no immunoreactivity for gamma-synuclein is seen in medulloblastomas. (PMID:12783249)
• Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson’s disease. (PMID:12867415)
• 2 new AA changes were found in unrelated Lewy body dementia index cases: V70M & P123H, at conserved residues in highly conserved regions of the beta-synuclein protein. Mutations in the beta-synuclein gene may predispose to DLB. (PMID:15365127)
• the alpha- and gamma-synucleins regulate proteasomal function and beta-synuclein acts as a negative regulator of alpha-synuclein (PMID:15591046)
• An 11-residue deletion in the lipid-binding domain of beta-synuclein leads to the destabilization of an entire segment of the micelle-bound helical structure containing the deletion site. (PMID:16597821)
• findings indicate that increased expression of beta-synuclein protein results in a reduction of alpha-synuclein protein expression (PMID:16959793)
• The accumulation of beta-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of alpha- and beta-synucleins in human lipidoses may be related to functional differences between these two proteins. (PMID:17653558)
• A comparison of the structural and dynamic properties of the free states of all three synucleins, is reported in order to shed light on differences that may help to explain their different propensities to aggregate. (PMID:17681534)
• Our data confirm the fatty acid binding properties of alpha-syn, and to a lesser extent beta-syn, but suggest that gamma-syn does not share this same characteristic. (PMID:17692832)
• structural and functional properties of beta-synuclein were characterized using biochemical and bio-physical methods including: a functional assay, mass spectrometry, size exclusion chromatography, circular dichroism (CD), and fluorescence spectroscopy (PMID:18221001)
• The aggregation behavior of alpha- and beta-synuclein as well as a series of chimeric variants were compared by exploring the structural transitions that occur in the presence of a widely used lipid mimetic, sodium dodecyl sulfate (SDS). (PMID:18436957)
• Gamma-synuclein protein is valuable for evaluation of progression of colorectal carcinoma; it is more sensitive to predict advanced stage and lymph node invasion when combined with either alpha- or beta-synuclein protein. (PMID:20043104)
• Data show that alpha-synuclein, beta-synuclein, and apolipoprotein A-1 have the conserved functional ability to induce membrane curvature and to convert large vesicles into highly curved membrane tubules and vesicles. (PMID:20693280)
• members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing diffuse lewy body disease. (PMID:20697047)
• Human beta-synuclein rendered fibrillogenic by designed mutations. (PMID:20833719)
• beta-Synuclein mRNA expression in the control group was significantly higher than that in the schizophrenic group. (PMID:20854101)
• A drastic diminution of beta-synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology (PMID:20959308)
• Studies identified molecular interaction domains within the beta-synuclein polypeptide that specifically binds alpha-synuclein. (PMID:21085664)
• Thermodynamic studies in conjunction with EPR confirm that alpha-synuclein, beta-synuclein, and gamma-synuclein bind copper(II) in a high affinity 1:1 stoichiometry. (PMID:21117662)
• Transcriptional regulation of the beta-synuclein 5’-promoter metal response element by metal transcription factor-1. (PMID:21386983)
• Synuclein-alpha, -beta, and -gamma are important in regulating neurotransmitter release from specific populations of midbrain dopamine neurons through mechanisms that differ from those reported in other neurons. (PMID:21593311)
• This study suggested that the pathogenesis of dementia in Parkinson disease, indicating that differential sncb expression in the caudate nucleus may represent one of the molecular mechanisms involved in these complex diseases. (PMID:21683963)
• Despite both synucleins sharing considerable sequence homology, the level of carboxy-terminal Src kinase-homologous kinase (CHK) phosphorylation of beta-synuclein is significantly higher than that of alpha-synuclein. (PMID:21699177)
• Data provide evidence for the role of beta-synuclein minor transcript variants in the development of complex diseases and provide new insights into the pathogenesis of Lewy body diseases. (PMID:22205345)
• both alphaS- and P123H betaS-globules were formed through similar but distinct pathogenic mechanisms. (PMID:23013868)
• In vivo cross-linking reveals principally oligomeric forms of alpha-synuclein and beta-synuclein in neurons and non-neural cells (PMID:23319586)
• Beta-synuclein protects against isoaspartate accumulation in alpha-synuclein. (PMID:23630590)
• The differing aggregation propensities of alpha-synuclein and beta-synuclein are associated with differences in the degree of residual structure in the C-terminus coupled to the shorter separation between the N- and C-termini in beta-synuclein. (PMID:25389903)
• beta-Synuclein expression was locally concentrated and rather modest, but nevertheless changed its effect on amyloid precursor protein expression and plaque load in a time- and concentration-dependent manner. (PMID:26111745)
• loss of inhibitory C-terminal conformations in disease associated P123H beta-synuclein (PMID:26332674)
• Cellular pathways affected by bSyn are similar to those affected by aSyn, including impairment of vesicular trafficking and induction of oxidative stress. (PMID:26586132)
• Data suggest that pH serves as an on/off switch for beta- synuclein to form aggregates/fibrils (as seem in Parkinson disease); hydrogen bonding between glutamate residues appears to be involved in fibril formation. (PMID:28710275)
• Cells that overexpress alpha-syn showed increased susceptibility to the toxicity of the oligomers, while those that overexpressed beta-syn showed increased resistance to the toxic oligomers. (PMID:29054856)
• Study suggests that beta-synuclein changes in Dementia with Lewy bodies may exacerbate neuronal dysfunction caused by accumulation of alpha-synuclein by influencing protein degradation. (PMID:29278715)
• Results show that the non-amyloid-beta component domain of SNCB is the primary determinant of self-association leading to fibril formation, while the N- and C-terminal domains play critical roles in the fibril inhibition process. These data provide evidence that all three domains together contribute to providing effective inhibition. (PMID:29782835)
• alterations in the plasma alpha-synuclein and beta-synuclein levels might be implicated in the association between synaptic abnormalities and autism spectrum disorder pathogenesis. (PMID:29850516)
• These studies could be helpful in understanding collective human synuclein behavior in various protein environments and in the modulation of the homeostasis between beta-syn and healthy versus corrupt alpha- and gamma-syn that can potentially affect PD pathology. (PMID:29851342)
• This analyzed identify functional insertion and deletion (INDEL) variations upstream of SNCB, determined SNCB expression levels, and correlated INDEL lengths with expression levels. (PMID:30040713)
• Vibrational Circular Dichroism Sheds New Light on the Competitive Effects of Crowding and beta-Synuclein on the Fibrillation Process of alpha-Synuclein. (PMID:30239196)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sncb	ENSDARG00000104945
mus_musculus	Sncb	ENSMUSG00000034891
rattus_norvegicus	Sncb	ENSRNOG00000018039

Paralogs (2): SNCA (ENSG00000145335), SNCG (ENSG00000173267)

Protein

Protein identifiers

Beta-synuclein — Q16143 (reviewed: Q16143)

All UniProt accessions (2): Q16143, G4Y816

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed predominantly in brain; concentrated in presynaptic nerve terminals.

Post-translational modifications. Phosphorylated. Phosphorylation by G-protein coupled receptor kinases (GRK) is more efficient than phosphorylation by CK1, CK2 and CaM-kinase II.

Similarity. Belongs to the synuclein family.

RefSeq proteins (7): NP_001001502, NP_001304963, NP_001304964, NP_001304965, NP_001304966, NP_001350069, NP_003076* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001058	Synuclein	Family
IPR002461	Synuclein_beta	Family

Pfam: PF01387

UniProt features (9 total): repeat 4, region of interest 2, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16143-F1	61.29	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 118

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5660489	MTF1 activates gene expression
R-HSA-5660526	Response to metal ions
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 146 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, AP1_01, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, CACCAGC_MIR138, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_CELL_CELL_SIGNALING, MODULE_66, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, GOBP_CELL_JUNCTION_ORGANIZATION, AP1_Q4_01, GOBP_DOPAMINE_METABOLIC_PROCESS, TGCTGAY_UNKNOWN, BACH2_01

GO Biological Process (6): chemical synaptic transmission (GO:0007268), dopamine metabolic process (GO:0042417), negative regulation of neuron apoptotic process (GO:0043524), synaptic vesicle endocytosis (GO:0048488), synapse organization (GO:0050808), neuron apoptotic process (GO:0051402)

GO Molecular Function (5): phospholipase inhibitor activity (GO:0004859), calcium ion binding (GO:0005509), transition metal ion binding (GO:0046914), cuprous ion binding (GO:1903136), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), inclusion body (GO:0016234), neuronal cell body (GO:0043025), axon terminus (GO:0043679), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Response to metal ions	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	2
intracellular anatomical structure	2
cellular anatomical structure	2
anterograde trans-synaptic signaling	1
catecholamine metabolic process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
cell junction organization	1
apoptotic process	1
glycerophospholipase activity	1
lipase inhibitor activity	1
copper ion binding	1
binding	1
cytoplasm	1
somatodendritic compartment	1
cell body	1
neuron projection terminus	1
presynapse	1
distal axon	1
cell junction	1

Protein interactions and networks

STRING

2075 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNCB	UCHL1	P09936	667
SNCB	SNCAIP	Q9Y6H5	655
SNCB	MAPT	P10636	645
SNCB	LRRK2	Q5S007	617
SNCB	GBA1	P04062	608
SNCB	PRKN	O60260	592
SNCB	PRNP	P04156	566
SNCB	SLC6A3	Q01959	562
SNCB	SNCA	P37840	562
SNCB	BLVRB	P30043	555
SNCB	VAMP2	P19065	549
SNCB	ATP13A2	Q9NQ11	537
SNCB	PSEN2	P49810	531
SNCB	ALAS2	P22557	510
SNCB	CKB	P12277	506

IntAct

47 interactions, top by confidence:

A	B	Type	Score
SNCB	MORN4	psi-mi:“MI:0915”(physical association)	0.720
MORN4	SNCB	psi-mi:“MI:0915”(physical association)	0.720
COPS3	SNCB	psi-mi:“MI:0915”(physical association)	0.560
PIAS1	SNCB	psi-mi:“MI:0915”(physical association)	0.560
RYBP	SNCB	psi-mi:“MI:0915”(physical association)	0.560
SKIC8	SNCB	psi-mi:“MI:0915”(physical association)	0.560
APP	SNCB	psi-mi:“MI:0915”(physical association)	0.560
SNCA	SNCB	psi-mi:“MI:0915”(physical association)	0.560
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
SNCAIP	SNCB	psi-mi:“MI:0915”(physical association)	0.400
AKT1	SNCB	psi-mi:“MI:0915”(physical association)	0.370
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
NUFIP1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
DGUOK	DNM1L	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
ARMC1	GNAO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): SNCB (Affinity Capture-MS), SNCB (Affinity Capture-MS), SNCB (Affinity Capture-MS), SNCB (Affinity Capture-MS), SNCB (Two-hybrid), SNCB (Affinity Capture-MS), SNCB (Affinity Capture-MS), SNCB (Affinity Capture-MS), SNCB (Affinity Capture-MS), MORN4 (Two-hybrid), SNCA (Affinity Capture-Western), SNCB (Affinity Capture-MS), SNCB (Reconstituted Complex), SNCB (Affinity Capture-MS), SNCB (Biochemical Activity)

ESM2 similar proteins: A0A0E4AVP3, A2XG55, A3AHG5, O36029, O55042, O76070, O94724, P01094, P0CU49, P16547, P22943, P23283, P33567, P37377, P37379, P37840, P53707, P61138, P61139, P61140, P61141, P61142, P61143, P61144, P61145, P61146, P61147, Q15847, Q16143, Q2PFW6, Q39846, Q3I5G7, Q3T0G8, Q42512, Q5XF06, Q63544, Q63754, Q6TMJ3, Q8LFD5, Q91448

Diamond homologs: O55042, P33567, P37377, P37840, P61138, P61139, P61140, P61141, P61142, P61143, P61144, P61145, P61146, P61147, Q16143, Q3I5G7, Q3T0G8, Q63754, Q91448, Q91ZZ3, O76070

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CHEK1	unknown	SNCB	phosphorylation
PLK1	“down-regulates activity”	SNCB	phosphorylation
PLK2	“down-regulates activity”	SNCB	phosphorylation
PLK3	“down-regulates activity”	SNCB	phosphorylation
GRK5	“down-regulates activity”	SNCB	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

24 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
7025	NM_003085.5(SNCB):c.208G>A (p.Val70Met)	Pathogenic

SpliceAI

1195 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176621208:CCTCA:C	donor_loss	1.0000
5:176621209:CTCAC:C	donor_loss	1.0000
5:176621210:TCA:T	donor_loss	1.0000
5:176621211:CACC:C	donor_loss	1.0000
5:176621212:A:T	donor_loss	1.0000
5:176621213:C:CG	donor_loss	1.0000
5:176621300:CTGG:C	acceptor_gain	1.0000
5:176621301:TGG:T	acceptor_gain	1.0000
5:176621302:GG:G	acceptor_gain	1.0000
5:176621303:GCT:G	acceptor_loss	1.0000
5:176621304:C:CA	acceptor_loss	1.0000
5:176621304:C:CC	acceptor_gain	1.0000
5:176621305:T:A	acceptor_loss	1.0000
5:176628666:G:C	donor_gain	1.0000
5:176629528:A:AC	donor_gain	1.0000
5:176629528:AC:A	donor_gain	1.0000
5:176629529:C:CC	donor_gain	1.0000
5:176629529:CC:C	donor_gain	1.0000
5:176629529:CCCA:C	donor_gain	1.0000
5:176629532:A:AC	donor_gain	1.0000
5:176629533:C:CC	donor_gain	1.0000
5:176629533:CCGA:C	donor_gain	1.0000
5:176629548:C:CA	donor_gain	1.0000
5:176629551:T:TA	donor_gain	1.0000
5:176630274:CCTCA:C	donor_loss	1.0000
5:176630275:CTCA:C	donor_loss	1.0000
5:176630276:TCACC:T	donor_loss	1.0000
5:176630277:CA:C	donor_loss	1.0000
5:176621311:C:CT	acceptor_gain	0.9900
5:176628665:A:AC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000868340 (5:176625441 C>T), RS1000911301 (5:176625359 G>A,C,T), RS1000994975 (5:176630524 G>A), RS1001048750 (5:176630335 G>C), RS1001131776 (5:176631619 T>C), RS1001256148 (5:176622110 T>C), RS1001982378 (5:176624165 C>T), RS1002076547 (5:176628187 G>A), RS1002134149 (5:176630238 A>C,G), RS1002185238 (5:176623987 G>T), RS1002268016 (5:176623936 G>A,C), RS1002685028 (5:176623615 G>A,T), RS1002930237 (5:176623098 G>A), RS1003086669 (5:176629186 T>C), RS1003346373 (5:176626976 A>T)

Disease associations

OMIM: gene MIM:602569 | disease phenotypes: MIM:127750

GenCC curated gene-disease

Disease	Classification	Inheritance
Lewy body dementia	Moderate	Unknown

Mondo (1): Lewy body dementia (MONDO:0007488)

Orphanet (1): NON RARE IN EUROPE: Dementia with Lewy body (Orphanet:1648)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000726	Dementia
HP:0000746	Delusion
HP:0001300	Parkinsonism
HP:0002367	Visual hallucination
HP:0007159	Fluctuations in consciousness
HP:0100315	Lewy bodies

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Synuclein proteins

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	affects binding, increases reaction, increases methylation	2
Cadmium Chloride	increases expression	2
pirinixic acid	decreases expression, increases activity, affects binding	1
ethyl-p-hydroxybenzoate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	decreases methylation	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Valproic Acid	affects expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Antirheumatic Agents	decreases expression	1
Butyric Acid	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 induced pluripotent stem cell, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_DX11	HAP1 SNCB (-)	Cancer cell line	Male
CVCL_DX61	HAP1 SNCA (-) SNCB (-)	Cancer cell line	Male
CVCL_E7NP	KOLF2.1J SNCB 9.0kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_E7P5	KOLF2.1J SNCB P123H SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7P6	KOLF2.1J SNCB P123H SNV/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

204 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00855686	PHASE4	COMPLETED	Memantine Versus Placebo in Parkinson’s Disease Dementia or Dementia With Lewy Bodies
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT01023672	PHASE4	COMPLETED	Pilot Study of Armodafinil in Patients With Dementia With Lewy Bodies
NCT02345213	PHASE4	COMPLETED	A Post-Marketing Clinical Study of Aricept in Patients With Dementia With Lewy Bodies (DLB)
NCT03582488	PHASE4	ENROLLING_BY_INVITATION	Longitudinal Imaging Biomarkers of Disease Progression in DLB
NCT03924414	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Parkinson’s And Zoledronic Acid
NCT04117178	PHASE4	COMPLETED	Monitoring Anti-Dementia Drugs by Serum Levels
NCT05514106	PHASE4	ENROLLING_BY_INVITATION	MIBG in Aging and Neurologic Disorders
NCT05590637	PHASE4	RECRUITING	Comparing Antipsychotic Medications in LBD Over Time
NCT06263673	PHASE4	COMPLETED	Anti-Diabetic Medications to Fight PD and LBD
NCT07284290	PHASE4	RECRUITING	Elucidating the Role of Cholinergic Degeneration in Cognitive Fluctuations in Lewy Body Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00230997	PHASE3	COMPLETED	Safety and Efficacy of Galantamine in Patients With Dementia With Lewy Bodies
NCT01278407	PHASE3	COMPLETED	A Study of E2020 in Patients With Dementia With Lewy Bodies (DLB), Followed by a Long-term Extension Phase
NCT01577394	PHASE3	COMPLETED	Oculomotor Testing in the Differential Diagnosis of Dementia
NCT04706910	PHASE3	RECRUITING	18F-DOPA II - PET Imaging Optimization
NCT05428475	PHASE3	UNKNOWN	Implementation and Evaluation of Improved Access to Medical Imaging for Geriatric Patients of The Royal Ottawa Hospital
NCT00543855	PHASE2	COMPLETED	A Double-blind Study of E2020 (Donepezil Hydrochloride) in Patients With Dementia With Lewy Bodies (DLB) (Study E2020-J081-431)
NCT00598650	PHASE2	COMPLETED	A Long-term, Extension Study of E2020 in Patients With Dementia With Lewy Bodies
NCT00630500	PHASE2	COMPLETED	Efficacy and Safety of Memantine for Parkinson’s Disease Dementia (PDD) and Dementia With Lewy Bodies (DLB)
NCT02640729	PHASE2	COMPLETED	Study Evaluating Nelotanserin for Treatment of Visual Hallucinations in Subjects With Lewy Body Dementia
NCT02669433	PHASE2	COMPLETED	Study Evaluating Intepirdine (RVT-101) in Subjects With Dementia With Lewy Bodies: The HEADWAY-DLB Study
NCT02702102	PHASE2	COMPLETED	Imaging Inflammation in Patients With Parkinson’s Disease Dementia or Dementia With Lewy Bodies
NCT02708186	PHASE2	COMPLETED	Study Evaluating Nelotanserin for Treatment of REM Sleep Behavior Disorder in Subjects With Dementia (DLB or PDD)
NCT02871427	PHASE2	TERMINATED	Open-label Study of Nelotanserin in Lewy Body Dementia With Visual Hallucinations or REM Sleep Behavior Disorder
NCT02910102	PHASE2	COMPLETED	Study Evaluating Intepirdine (RVT-101) on Gait and Balance in Subjects With Dementia
NCT03305809	PHASE2	COMPLETED	A Study of LY3154207 in Participants With Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson’s Disease (PD) or Dementia With Lewy Bodies (DLB)
NCT03467152	PHASE2	COMPLETED	Study To Evaluate the Efficacy, Safety and Tolerability of E2027 (Hereinafter Referred to as Irsenontrine) in Participants With Dementia With Lewy Bodies
NCT03538522	PHASE2	COMPLETED	A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831
NCT03592862	PHASE2	WITHDRAWN	A Study to Assess Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies
NCT03888222	PHASE2	COMPLETED	Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies
NCT03996460	PHASE2	RECRUITING	K0706 for Patients Diagnosed With Dementia With Lewy Bodies
NCT04001517	PHASE2	COMPLETED	Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies
NCT04002674	PHASE2	COMPLETED	Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies
NCT04148391	PHASE2	ACTIVE_NOT_RECRUITING	NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson’s Disease or Lewy Body Dementia (Cognition, Memory, Attention, Thinking)
NCT04167813	PHASE2	UNKNOWN	Trial of Ondansetron as a Parkinson’s HAllucinations Treatment
NCT04588285	PHASE2	RECRUITING	Ambroxol in New and Early DLB, A Phase IIa Multicentre Randomized Controlled Double Blind Clinical Trial
NCT04764669	PHASE2	COMPLETED	A Study of E2027 in Participants With Dementia With Lewy Bodies (DLB) or Parkinson’s Disease Dementia (PDD) With or Without Amyloid Copathology
NCT04786223	PHASE2	ENROLLING_BY_INVITATION	Targeting Neuroinflammation as a Contributing Pathology in Alzheimer’s Disease Dementia and Related Dementias
NCT04831281	PHASE2	TERMINATED	ATH-1017 Treatment in Subjects With Parkinson’s Disease Dementia or Dementia With Lewy Bodies (SHAPE Trial)