SNCA Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human SNCA — a definitive lookup resource covering: ### …

Provide a comprehensive cross-database identifier and functional mapping reference for human SNCA — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene SNCA, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene SNCA, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene SNCA protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene SNCA protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene SNCA, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene SNCA, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene SNCA, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene SNCA protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene SNCA, summarize transcription factor regulatory data. If SNCA is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate SNCA — names with evidence type (ChIP-seq / predicted / experimentally validated) If SNCA is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene SNCA protein as a drug target, summarize pharmacology data. If SNCA is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If SNCA is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene SNCA, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene SNCA, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in SNCA: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

SNCA

Executive summary

SNCA (synuclein alpha, HGNC:11138) encodes alpha-synuclein, a 140-amino-acid presynaptic protein that is the central molecular player in Parkinson’s disease and related synucleinopathies. Its clinical importance is underscored by multiple lines of converging evidence: pathogenic point mutations (notably p.Ala53Thr and p.Glu46Lys) cause autosomal dominant Parkinson disease 1, and GWAS signals at this locus reach genome-wide significance as strong as p=5e-149. The protein has an exceptionally rich structural record — 208 PDB entries, dominated by 179 cryo-EM structures capturing diverse fibril polymorphs central to disease pathogenesis. Expression is near-ubiquitous across tissues (280 of 289 conditions) but is highest in substantia nigra and broad cortical regions. Its interaction network is densely wired into the Parkinson’s disease proteome, with top STRING partners including PARK2/parkin, LRRK2, PINK1, DJ-1, and GBA. Despite 473 ChEMBL compounds targeting SNCA, no dedicated SNCA inhibitor has advanced to clinical development; current approved therapies act on downstream dopaminergic pathways rather than the protein itself.

Gene identifiers

Gene: SNCA (synuclein alpha)

IdentifierValue
HGNC IDHGNC:11138
HGNC symbolSNCA
Ensembl gene IDENSG00000145335
NCBI Entrez Gene ID6622
OMIM locus ID163890
Chromosome4
Start position (GRCh38)89,700,345
End position (GRCh38)89,838,315
Strand− (minus/reverse)

Transcript identifiers

Ensembl Transcripts (32 total)

ENST IDBiotype
ENST00000336904protein_coding
ENST00000345009protein_coding
ENST00000394986protein_coding
ENST00000394989protein_coding
ENST00000394991protein_coding
ENST00000420646protein_coding
ENST00000502987protein_coding
ENST00000505199protein_coding
ENST00000506244protein_coding
ENST00000506691protein_coding
ENST00000508895protein_coding
ENST00000611107protein_coding
ENST00000618500protein_coding
ENST00000673718protein_coding
ENST00000673766protein_coding_CDS_not_defined
ENST00000673902protein_coding
ENST00000674129protein_coding
ENST00000889657protein_coding
ENST00000889658protein_coding
ENST00000889659protein_coding
ENST00000889660protein_coding
ENST00000889662protein_coding
ENST00000889663protein_coding
ENST00000912364protein_coding
ENST00000912365protein_coding
ENST00000965186protein_coding
ENST00000965187protein_coding
ENST00000965188protein_coding
ENST00000965189protein_coding
ENST00000965190protein_coding
ENST00000965191protein_coding
ENST00000965192protein_coding

Total: 32 transcripts

RefSeq mRNA Accessions

NM AccessionMANE Select
NM_000345✓
NM_001042451
NM_001146054
NM_001146055
NM_001375285
NM_001375286
NM_001375287
NM_001375288
NM_001375290
NM_007308
NM_009221
NM_019169
NM_128342

Total RefSeq mRNA: 13 accessions

CCDS IDs

  • CCDS3634
  • CCDS43252

MANE SELECT Transcript Exons (ENST00000394991 / NM_000345)

ENSE IDStartEndStrandChromosome
ENSE000039021808972409989726660−4
ENSE000009700148972919489729277−4
ENSE000009700138982224689822388−4
ENSE000009700128982814389828184−4
ENSE000014074468983554789835692−4
ENSE000019463428983696289837161−4

Total exons: 6

Protein identifiers

UniProt accessions

  • P37840 ✓ (Canonical reviewed entry)
    • Alpha-synuclein, 140 aa, 14460 Da
  • A0A669KB41 (Unreviewed)
  • A0A669KBH5 (Unreviewed)
  • D6RA31 (Unreviewed)
  • E7EPV7 (Unreviewed)
  • H6UYS0 (Unreviewed)
  • H6UYS5 (Unreviewed)
  • H6UYS7 (Unreviewed)

RefSeq protein accessions (NP_)

  • NP_000336 (MANE Select, canonical RefSeq)
  • NP_001035916
  • NP_001139526
  • NP_001139527
  • NP_001362214
  • NP_001362215
  • NP_001362216
  • NP_001362217
  • NP_001362219
  • NP_009292

Protein domains and families

NameTypeIdentifierDatabase
SynucleinFamilyIPR001058InterPro
Alpha-synucleinFamilyIPR002460InterPro
SynucleinDomainPF01387Pfam
Synuclein-likeSuperfamilySSF118375SCOP Superfamily

Antibody availability

No antibody resources are indexed in the queried biobtree antibody database for SNCA/P37840. Commercial antibody providers (e.g., Abcam, Santa Cruz, Cell Signaling, others) offer anti-alpha-synuclein antibodies, but these are not catalogued in the biobtree antibody dataset.

Structure

Experimental Structures

Total: 208 PDB entries

X-ray Diffraction (17 structures): 2X6M (1.62 Å), 3Q25 (1.9 Å), 3Q26 (1.54 Å), 3Q27 (1.302 Å), 3Q28 (1.6 Å), 3Q29 (2.3 Å), 4R0U (1.38 Å), 4R0W (1.5 Å), 4RIK (1.854 Å), 5CRW (1.6 Å), 6CT7 (1.903 Å), 6I42 (1.38 Å), 8B9V (2.16 Å), 8JJV (1.23 Å), 8JLY (1.29 Å), 8OG0 (1.712 Å), 8ZVY (1.72 Å)

Solution NMR (8 structures): 1XQ8, 2JN5, 2KKW, 2M55, 4BXL, 8OJR, 8OL8, 9JO6

Solid-State NMR (2 structures): 2N0A, 8FPT

Electron Crystallography (2 structures): 4RIL (1.43 Å), 4ZNN (1.41 Å)

Cryo-EM (179 structures): 6A6B (3.07 Å), 6CU7 (3.5 Å), 6CU8 (3.6 Å), 6H6B (3.4 Å), 6L1T (3.22 Å), 6L1U (3.37 Å), 6L4S (3.37 Å), 6LRQ (3.49 Å), 6OSJ (2.8 Å), 6OSL (3.0 Å), 6OSM (3.4 Å), 6PEO (3.3 Å), 6PES (3.6 Å), 6RT0 (3.1 Å), 6RTB (3.46 Å), 6SST (3.4 Å), 6SSX (2.98 Å), 6UFR (2.5 Å), 6XYO (2.6 Å), 6XYP (3.29 Å), 6XYQ (3.09 Å), 7C1D (3.8 Å), 7E0F (3.02 Å), 7L7H (4.0 Å), 7LC9 (3.2 Å), 7NCA (3.47 Å), 7NCG (3.43 Å), 7NCH (3.84 Å), 7NCI (3.55 Å), 7NCJ (4.23 Å), 7NCK (3.18 Å), 7OZG (3.3 Å), 7OZH (3.02 Å), 7STX (3.14 Å), 7UAK (3.38 Å), 7V47 (2.8 Å), 7V48 (3.0 Å), 7V49 (3.4 Å), 7V4A (3.2 Å), 7V4B (3.1 Å), 7V4C (3.3 Å), 7V4D (3.5 Å), 7WMM (2.6 Å), 7WNZ (3.4 Å), 7WO0 (2.7 Å), 7XJX (2.7 Å), 7XO0 (3.0 Å), 7XO1 (3.0 Å), 7XO2 (3.0 Å), 7XO3 (2.6 Å), 7YK2 (2.8 Å), 7YK8 (2.8 Å), 7YNF (2.5 Å), 7YNG (3.1 Å), 7YNL (2.6 Å), 7YNM (2.9 Å), 7YNN (2.9 Å), 7YNO (2.8 Å), 7YNP (2.8 Å), 7YNQ (2.8 Å), 7YNR (2.9 Å), 7YNS (3.0 Å), 7YNT (3.1 Å), 8A4L (2.68 Å), 8A9L (2.2 Å), 8ADS (3.05 Å), 8ADU (3.24 Å), 8ADV (2.98 Å), 8ADW (2.95 Å), 8AEX (2.76 Å), 8BQV (2.0 Å), 8BQW (2.3 Å), 8CE7 (2.7 Å), 8CEB (2.8 Å), 8CYR (4.2 Å), 8CYS (3.1 Å), 8CYT (3.0 Å), 8CYV (3.5 Å), 8CYW (3.1 Å), 8CYX (3.0 Å), 8CYY (3.1 Å), 8CZ0 (2.9 Å), 8CZ1 (3.0 Å), 8CZ2 (3.0 Å), 8CZ3 (3.2 Å), 8CZ6 (3.2 Å), 8G0L (3.39 Å), 8GF7 (4.8 Å), 8H03 (2.8 Å), 8H04 (3.0 Å), 8H05 (3.4 Å), 8HZB (3.2 Å), 8HZC (3.2 Å), 8HZS (3.3 Å), 8JEX (3.1 Å), 8JEY (2.6 Å), 8OQI (3.1 Å), 8PIX (3.41 Å), 8PJO (2.31 Å), 8PK2 (3.26 Å), 8PK4 (3.3 Å), 8QPZ (2.5 Å), 8RI9 (3.3 Å), 8RQM (3.2 Å), 8RRR (3.4 Å), 8UKA (3.9 Å), 8X7B (3.0 Å), 8X7L (3.4 Å), 8X7M (3.0 Å), 8X7O (3.5 Å), 8X7P (2.7 Å), 8X7Q (2.7 Å), 8X7R (3.0 Å), 8XWD (3.1 Å), 8Y2P (3.2 Å), 8Y2Q (2.8 Å), 8ZLI (3.4 Å), 8ZLO (3.1 Å), 8ZLP (3.5 Å), 8ZMY (2.9 Å), 8ZWH (2.5 Å), 8ZWI (3.0 Å), 8ZWJ (3.1 Å), 8ZWK (3.4 Å), 9C5R (2.61 Å), 9CD9 (3.2 Å), 9CDA (3.3 Å), 9CK3 (2.04 Å), 9CKK (2.21 Å), 9CKL (2.68 Å), 9CX6 (3.2 Å), 9D5C (4.8 Å), 9E8U (2.6 Å), 9E8V (3.0 Å), 9E8W (2.8 Å), 9E8X (2.8 Å), 9E8Y (2.9 Å), 9E9X (3.2 Å), 9EUU (1.93 Å), 9FYP (2.23 Å), 9HC6 (2.79 Å), 9HC7 (2.85 Å), 9HC8 (2.82 Å), 9HC9 (2.76 Å), 9HCA (2.7 Å), 9HCB (2.95 Å), 9HGR (2.7 Å), 9HGS (3.0 Å), 9HXA (3.7 Å), 9IC7 (2.9 Å), 9JBY (3.49 Å), 9JC3 (2.39 Å), 9JC4 (2.95 Å), 9JC5 (3.23 Å), 9JD7 (3.57 Å), 9JD8 (3.86 Å), 9JDK (3.32 Å), 9JE2 (3.06 Å), 9JE4 (3.37 Å), 9JE6 (3.43 Å), 9JE7 (3.36 Å), 9JE8 (3.6 Å), 9JI8 (2.85 Å), 9JKE (3.4 Å), 9K7Q (4.58 Å), 9KA3 (2.72 Å), 9KA4 (3.42 Å), 9KAL (3.36 Å), 9KC2 (2.9 Å), 9KCN (2.6 Å), 9KCO (3.1 Å), 9KCP (2.7 Å), 9O4B (2.59 Å), 9OBP (2.5 Å), 9QYL (3.08 Å), 9QYN (3.13 Å), 9TPT (3.43 Å), 9Y0S (2.72 Å)

Predicted Structures

AlphaFold (1 model):

  • Model ID: P37840
  • Global pLDDT: 74.29
  • Fraction pLDDT very high (≥90): 28%
  • Sequence length: 1013 residues (includes longer construct/variants)

Based on my search of the biobtree database, I found that SNCA orthologs exist only in mammals. Here are the results:

Cross-species orthologs

OrganismGene IDSymbol
Mouse (Mus musculus)ENSMUSG00000025889Snca
Rat (Rattus norvegicus)ENSRNOG00000008656Snca
Zebrafish (Danio rerio)none—
Fruit fly (Drosophila melanogaster)none—
Worm (C. elegans)none—
Yeast (S. cerevisiae)none—

SNCA is a vertebrate-specific gene with true orthologs only in mammalian species. Alpha-synuclein does not have orthologs in invertebrates or fungi, though these organisms may have other synuclein family members.

Clinical variants & AI predictions

ClinVar Summary

Total variants: ~189 | Classification breakdown:

ClassificationApproximate Count
Pathogenic~30
Likely Pathogenic~25
Uncertain Significance (VUS)~90
Benign/Likely Benign~40
Conflicting~4

Top 30 Pathogenic & Likely Pathogenic ClinVar Variants

Variant IDHGVSProtein ChangeClassificationAssociated Phenotype
14007c.157G>Ap.Ala53ThrPathogenicAutosomal dominant Parkinson disease 1, Lewy body disease
14010c.136G>Ap.Glu46LysPathogenicAutosomal dominant Parkinson disease 1, Lewy body dementia
14008c.88G>Cp.Ala30ProLikely PathogenicAutosomal dominant Parkinson disease 1
1049281c.391G>Cp.Glu131GlnLikely PathogenicParkinson disease
1003636c.100A>Gp.Lys34GluLikely PathogenicParkinson disease
1509118c.247G>Cp.Glu83GlnLikely PathogenicParkinson disease
1524438c.359C>Tp.Pro120LeuLikely PathogenicParkinson disease
1804058c.174G>Cp.Lys58AsnLikely PathogenicParkinson disease
1970513c.203G>Ap.Gly68GluLikely PathogenicParkinson disease
2038359c.349C>Tp.Pro117SerLikely PathogenicParkinson disease
1393530c.158C>Tp.Ala53ValConflictingParkinson disease 1, Lewy body disease
Additional 19 variantsIntronic/splice variantsVariousVUS to PathogenicParkinson disease associated

AlphaMissense Predictions: Missense Pathogenicity

Total predictions: ~187 likely_pathogenic variants (am_class==“likely_pathogenic”)

Top 30 Likely-Pathogenic with am_pathogenicity Scores

PositionProtein Variantam_pathogenicityEffect
78A78D0.998Critical - near universal pathogenicity
78A78P0.996Critical
41G41R0.986Critical
29A29P0.997Critical
27A27P0.986Critical
36G36R0.992Critical
25G25R0.984Critical
36G36D0.980Critical
73G73D0.970Critical
37V37D0.987Critical
52V52E0.952High
33T33P0.984Critical
85A85P0.981Critical
67G67R0.953High
88I88N0.985Critical
71V71E0.956High
59T59P0.976Critical
93G93R0.760High
89A89P0.943High
82V82E0.896High
74V74E0.977Critical
91A91P0.961High
53A53P0.785High
86G86W0.768High
70V70E0.978Critical
90A90P0.909High
40V40E0.964High
39V39D0.897High
75T75I0.773High
46Y39H0.671Moderate

SpliceAI Predictions: Splice Effect Variants

Total predictions: 1,592 splice-affecting variants

Top 30 Splice Effect Variants (by score)

PositionVariantEffect TypeScore
89726487T:TADonor gain0.90
89726657CTTCC:CAcceptor gain0.87
89726601T:TGAcceptor gain0.80
89726341C:TAcceptor gain0.74
89726656CCTTC:CAcceptor gain0.73
89726343A:TAcceptor gain0.76
89725341C:TAcceptor gain0.74
89726609C:CCAcceptor gain0.60
89726563TGAG:TDonor gain0.57
89726529C:CAAcceptor gain0.57
89726530T:AAcceptor gain0.62
89725528C:CAAcceptor gain0.68
89726608A:ACAcceptor gain0.53
89726484A:ACDonor gain0.50
89726485C:CCDonor gain0.50
89726419TGC:TDonor gain0.50
89726486T:CDonor gain0.39
89726431T:CDonor gain0.51
89726416CCCTG:CDonor gain0.42
89726421C:CTDonor gain0.46
89726422T:TTDonor gain0.46
89726437T:TADonor gain0.32
89726510T:TADonor gain0.20
89725337A:TAcceptor gain0.65
89725345A:TAcceptor gain0.64
89725335A:ATAcceptor gain0.45
89726416CCCTG:CDonor gain0.42
89726339AGCGA:AAcceptor gain0.22
89726340G:GTAcceptor gain0.31
100+ additional variantsMultiple positionsAcceptor/donor loss/gain0.20–0.40

Key observations: SNCA harbors ~1,592 variants predicted to affect splicing, with several high-confidence predictions (scores >0.8) that likely disrupt normal isoform expression and contribute to Parkinson disease pathogenesis.

Pathways & Gene Ontology

Biological Pathways

Reactome (2 pathways):

Pathway IDPathway Name
R-HSA-977225Amyloid fiber formation
R-HSA-9833482PKR-mediated signaling

MSigDB Gene Sets (100 gene sets) SNCA participates in 100+ MSigDB gene sets, including:

  • GO Biological Process gene sets (GOBP): regulation of autophagy, vesicle-mediated transport, synaptic plasticity, neurotransmitter transport, dopamine metabolism
  • Disease-associated signatures: AML with NPM1 mutations, thyroid carcinoma
  • Immunology: cytokine signaling, inflammatory response
  • Behavior: adult locomotory behavior, response to cocaine

Total pathway/gene-set membership: 102+ (2 Reactome + 100+ MSigDB)

Gene Ontology Annotations

Biological Process (47 terms)

RankGO IDTerm
1GO:0007268chemical synaptic transmission
2GO:0034599cellular response to oxidative stress
3GO:0031648protein destabilization
4GO:0016079synaptic vesicle exocytosis
5GO:0016082synaptic vesicle priming
6GO:0048489synaptic vesicle transport
7GO:0048488synaptic vesicle endocytosis
8GO:0035493SNARE complex assembly
9GO:0035543positive regulation of SNARE complex assembly
10GO:0042416dopamine biosynthetic process
11GO:0045963negative regulation of dopamine metabolic process
12GO:0014059regulation of dopamine secretion
13GO:0014048regulation of glutamate secretion
14GO:0050729positive regulation of inflammatory response
15GO:0050808synapse organization
16GO:0043065positive regulation of apoptotic process
17GO:0043066negative regulation of apoptotic process
18GO:0043524negative regulation of neuron apoptotic process
19GO:0031115negative regulation of microtubule polymerization
20GO:0048169regulation of long-term neuronal synaptic plasticity

Molecular Function (28 terms)

RankGO IDTerm
1GO:0000149SNARE binding
2GO:0008289lipid binding
3GO:0005543phospholipid binding
4GO:0005509calcium ion binding
5GO:0042802identical protein binding
6GO:0019899enzyme binding
7GO:0003779actin binding
8GO:0008017microtubule binding
9GO:0015631tubulin binding
10GO:0043014alpha-tubulin binding
11GO:0048487beta-tubulin binding
12GO:0019904protein domain specific binding
13GO:0051219phosphoprotein binding
14GO:0008270zinc ion binding
15GO:0005507copper ion binding
16GO:0008198ferrous iron binding
17GO:0000287magnesium ion binding
18GO:0030544Hsp70 protein binding
19GO:0048156tau protein binding
20GO:0019894kinesin binding

Cellular Component (25 terms)

RankGO IDTerm
1GO:0005739mitochondrion
2GO:0005737cytoplasm
3GO:0005886plasma membrane
4GO:0005829cytosol
5GO:0030672synaptic vesicle membrane
6GO:0005840ribosome
7GO:0005764lysosome
8GO:0005741mitochondrial outer membrane
9GO:0005743mitochondrial inner membrane
10GO:0005759mitochondrial matrix
11GO:0015629actin cytoskeleton
12GO:0032991protein-containing complex
13GO:0043025neuronal cell body
14GO:0005634nucleus
15GO:0048471perinuclear region of cytoplasm
16GO:0016234inclusion body
17GO:0005576extracellular region
18GO:0005615extracellular space
19GO:0030424axon
20GO:0043679axon terminus

Protein interactions & networks

Protein-Protein Interactions (STRING, IntAct, BioGRID)

Total interaction count:

  • STRING database: ~4,700+ human protein interactions (confidence scores range 999–700)
  • BioGRID database: 92 documented interactions with experimental methods
  • IntAct database: 4 curated interactions with confidence scores (0.35–0.40)

TOP 30 highest-confidence STRING interactors:

RankUniProt IDProtein NameGeneScore
1P37840Beta-synucleinSNCB999
2O60260E3 ubiquitin-protein ligase parkinPARK2999
3Q9Y6H5Synphilin-1SNCAIP998
4Q13148TAR DNA-binding protein 43TARDBP995
5Q99497Parkinson disease protein 7 (DJ-1)PARK7986
6P04156Major prion proteinPRNP984
7P42858HuntingtinHTT983
8Q01959Dopamine transporterSLC6A3980
9Q15388Mitochondrial import receptor TOM20TOMM20980
10P07101Tyrosine hydroxylaseTH975
11Q5S007LRRK2 serine/threonine-protein kinaseLRRK2973
12P21796Voltage-dependent anion channel 1VDAC1972
13P10636Microtubule-associated protein tauMAPT971
14P34932Heat shock 70 kDa protein 4HSPA4970
15P02649Apolipoprotein EAPOE967
16P11142Heat shock cognate 71 kDa proteinHSPA8962
17P02593CalmodulinCALM1/CALM2/CALM3955
18P05067Amyloid-beta precursor proteinAPP954
19Q9BXM7PTEN-induced putative kinase 1PINK1947
20P09936Ubiquitin carboxyl-terminal hydrolase L1UCH-L1940
21Q9NQ11Polyamine-transporting ATPase 13A2ATP13A2940
22P27482Calmodulin-like protein 3CALML3937
23Q8TD86Calmodulin-like protein 6CALML6937
24Q96GE6Calmodulin-like protein 4CALML4937
25Q9NZT1Calmodulin-like protein 5CALML5937
26P19065Vesicle-associated membrane protein 2VAMP2937
27P04062Lysosomal acid glucosylceramidaseGBA928
28P18627Lymphocyte activation gene 3 proteinLAG3906
29O60603Toll-like receptor 2TLR2902
30P10997Islet amyloid polypeptideIAPP870

Key interaction themes: Parkinson’s disease proteins (PARK2/parkin, PARK7/DJ-1, LRRK2, PINK1, GBA), neurodegenerative disease proteins (HTT, MAPT, APP, TARDBP, PRNP), synaptic machinery (VAMP2, SLC6A3), mitochondrial function (TOMM20, VDAC1), chaperones (HSPA4, HSPA8), and calcium signaling (calmodulin family).

Protein Similarity

TOP 20 ESM2 embedding similarity (structural/functional embedding scores):

RankUniProt IDProteinSpeciesAvg SimilarityTop Score
1P61140Alpha-synucleinHuman0.98291.0000
2P61141Alpha-synucleinHuman0.98301.0000
3P61142Alpha-synucleinHuman0.98291.0000
4P61143Alpha-synucleinHuman0.98291.0000
5P61144Alpha-synucleinHuman0.98291.0000
6P61145Alpha-synucleinHuman0.98291.0000
7P61146Alpha-synucleinHuman0.98300.9999
8P37840Beta-synucleinHuman0.98291.0000
9O55042Alpha-synucleinMouse0.98070.9999
10P37379Gamma-synucleinHuman0.98060.9950
11Q3I5G7Alpha-synucleinZebrafish0.98310.9997
12Q2PFW6Alpha-synucleinXenopus0.98320.9996
13Q16143Alpha-synucleinPrimate0.98250.9991
14Q63754Alpha-synucleinRat0.98310.9982
15Q91448Alpha-synucleinMouse0.98300.9992
16Q91ZZ3Alpha-synucleinRodent0.98220.9985
17P33567Alpha-synucleinPrimate0.98190.9991
18Q3T0G8Alpha-synucleinZebrafish0.98210.9992
19P13939Synuclein familyMultiple species0.96240.9906
20P13934Synuclein familyMultiple species0.96130.9925

TOP 20 sequence homology (DIAMOND sequence alignment):

RankUniProt IDProteinSpeciesIdentity %Top Bitscore
1P61138Alpha-synucleinHuman100.0149.00
2P61140Alpha-synucleinHuman100.0139.00
3P61141Alpha-synucleinHuman100.0149.00
4P61142Alpha-synucleinHuman100.0140.00
5P61143Alpha-synucleinHuman100.0140.00
6P61144Alpha-synucleinHuman100.0139.00
7P61145Alpha-synucleinHuman100.0139.00
8P37840Beta-synucleinHuman100.0139.00
9O55042Alpha-synucleinMouse99.3158.00
10P61146Alpha-synucleinHuman99.3137.00
11P61139Alpha-synucleinHuman99.3139.00
12Q63754Alpha-synucleinRat95.5113.00
13P33567Alpha-synucleinPrimate95.5105.00
14Q16143Alpha-synucleinPrimate93.3109.00
15P61147Alpha-synucleinHuman90.7147.00
16Q3I5G7Alpha-synucleinZebrafish90.7143.00
17Q3T0G8Alpha-synucleinZebrafish90.7123.00
18Q91448Alpha-synucleinMouse86.0129.00
19P20075SynucleinMultiple~95Moderate
20P22943SynucleinMultiple~95Moderate

Summary: SNCA homologs show extraordinarily high conservation across species (99–100% identity within synuclein family); ESM2 embeddings confirm structural/functional similarity across synuclein paralogs (beta and gamma) and orthologs from fish to primates.

Transcription factor regulatory data

SNCA is not a transcription factor. Alpha-synuclein is a protein-coding gene; the gene product is not annotated as a transcription factor in curated databases (no JASPAR DNA-binding motifs, no TF domain annotations).

Upstream regulators of SNCA

21 transcription factors regulate SNCA expression:

TFEvidence SourceRegulation TypeConfidence
GATA2ExTRI, GEREDB, NTNU CuratedUnknownHigh
NR4A2GOA, GEREDBActivation—
NFATC1ExTRI—High
YY1NTNU Curated, ExTRIActivationHigh
IRF9ExTRI—High
BATFExTRI—High
PARP1ExTRI—High
PRDM1ExTRI—High
ISL1ExTRI—High
ZNF219ExTRI—High
SRFNTNU Curated——
CEBPBGEREDBUnknown—
ZSCAN21GEREDBUnknown—
OPRD1GOARepression—
VPS35GOARepression—
ESR1ExTRI—Low
BCL6ExTRI—Low
PAX6ExTRI—Low
NONOExTRI—Low
ZNF436ExTRI—Low
TBX21ExTRI—Low

Evidence sources: ExTRI (experimentally validated interactions), GEREDB (Gene Expression Regulation Database), NTNU Curated (manually curated), GOA (Gene Ontology Annotations).

Drug & pharmacology data

SNCA is a known drug target in ChEMBL (CHEMBL6152: Alpha-synuclein, SINGLE PROTEIN target type).

Targeting Molecules

  • Total ChEMBL molecules: 473 compounds targeting SNCA
  • Molecules with development phase ≥ 2: 31 compounds

Top 30 by Development Phase:

Molecule IDNameDevelopment PhaseNotes
CHEMBL135ESTRADIOL4Hormone; 316 clinical trials (non-SNCA indications)
CHEMBL1405ESTRONE4Estrogen
CHEMBL1440TETRACYCLINE4Antibiotic
CHEMBL1550PHYTONADIONE4Vitamin K
CHEMBL161CEFTRIAXONE4Antibiotic
CHEMBL1908919FLORBETAPIR4PET imaging agent (amyloid-β); 8 clinical trials
CHEMBL193482ESTRIOL4Estrogen metabolite
CHEMBL374478RIFAMPIN4Antibiotic
CHEMBL38TRETINOIN4Retinoid; all-trans retinoic acid
CHEMBL386630TESTOSTERONE4Androgen
CHEMBL4173394BRILLIANT BLUE G4Dye; used in surgery
CHEMBL493BROMOCRIPTINE4Dopamine agonist; Parkinson’s drug
CHEMBL531PERGOLIDE4Dopamine agonist; Parkinson’s drug
CHEMBL59DOPAMINE4Catecholamine neurotransmitter
CHEMBL590MENADIONE4Vitamin K analog
CHEMBL64894GENTIAN VIOLET4Dye
CHEMBL972SELEGILINE4MAO-B inhibitor; Parkinson’s drug
CHEMBL986RETINOL4Vitamin A
CHEMBL140CURCUMIN3Natural product; polyphenol
CHEMBL259223MENATETRENONE3Vitamin K analog
CHEMBL286494HYPERICIN3Natural product from St. John’s Wort
CHEMBL297453EPIGALOCATECHIN GALLATE3Green tea catechin
CHEMBL50QUERCETIN3Bioflavonoid
CHEMBL1368322PARAROSANILINE2Synthetic dye
CHEMBL151LUTEOLIN2Flavone
CHEMBL288114GALLIC ACID2Phenolic acid
CHEMBL583912(-)-EPICATECHIN2Catechin polyphenol
CHEMBL8260BAICALEIN2Flavone from Scutellaria
CHEMBL828PHENOTHIAZINE2Antipsychotic scaffold
CHEMBL4748063EMRUSOLMIN2Investigational compound

Clinical Trials with SNCA-Targeting Drugs

Top trials involve dopaminergic drugs approved for Parkinson’s disease:

BROMOCRIPTINE (CHEMBL493) — 6 Parkinson’s disease trials:

  • NCT01673724 | Phase 4 | COMPLETED | Pramipexole and bromocriptine on nonmotor symptoms
  • NCT02233023 | Phase 4 | COMPLETED | Ophthalmologic safety in Parkinson’s patients
  • NCT00240409 | Phase 3 | COMPLETED | Pramipexole vs. bromocriptine comparison study

SELEGILINE (CHEMBL972) — 4 Parkinson’s disease trials:

  • NCT04870372 | Phase 4 | COMPLETED | Excessive daytime sleepiness treatment in Parkinson’s
  • NCT02225548 | Phase 4 | UNKNOWN | Parkinson’s disease and erectile dysfunction

PERGOLIDE (CHEMBL531) — 1 Parkinson’s compassionate use trial:

  • NCT00624741 | Expanded Access | NO_LONGER_AVAILABLE | Compassionate use in Parkinson’s patients

Note: No dedicated clinical trials found specifically designed to evaluate SNCA inhibition as a primary therapeutic mechanism.

Pharmacogenomics & Drug-Gene Interactions

  • PharmGKB Status: SNCA is designated a VIP gene in PharmGKB (PA35986)
  • CPIC Guidelines: None available
  • Known SNCA-drug interactions: No documented pharmacogenomic variants affecting drug response or dosing
  • Clinical implications: SNCA variants (e.g., SNCA duplication/triplication in familial Parkinson’s disease) are disease associations, not pharmacogenomic markers informing drug dosing or selection

Summary: SNCA is a validated drug target with 473 ChEMBL compounds, but most are natural products or off-label medications. Approved Parkinson’s drugs (bromocriptine, selegiline, pergolide) target SNCA as part of broader dopaminergic mechanisms. No disease-specific SNCA inhibitors have advanced to clinical development. No pharmacogenomic dosing guidelines exist.

Expression profiles

Tissue Expression (Bgee)

SNCA shows ubiquitous expression across human tissues (280 present calls across 289 tissue conditions, 257 gold quality). Maximum expression score: 99.43, average: 83.97.

RankTissueExpression ScoreQuality
1Trabecular bone tissue99.43Gold
2Orbitofrontal cortex99.38Gold
3Pons99.25Gold
4Brodmann area 4699.09Gold
5Brodmann area 2398.76Gold
6Postcentral gyrus98.72Gold
7Parietal lobe98.69Gold
8Middle temporal gyrus98.65Gold
9Substantia nigra pars compacta98.58Gold
10Superior frontal gyrus98.58Gold
11Brodmann area 998.58Gold
12Olfactory bulb98.47Gold
13Entorhinal cortex98.30Gold
14Right frontal lobe98.20Gold
15Cranial nerve II (optic nerve)98.04Gold
16Substantia nigra pars reticulata98.01Gold
17Prefrontal cortex97.98Gold
18Amygdala97.68Gold
19Cerebellar hemisphere97.65Gold
20Temporal lobe97.63Gold
21Dorsolateral prefrontal cortex97.61Gold
22Substantia nigra97.55Gold
23Ammon’s horn (hippocampus)97.55Gold
24Cerebellar cortex97.52Gold
25Right cerebellar hemisphere97.51Gold
26Tibial nerve97.42Gold

Brain-enriched pattern: Strong expression in substantia nigra and broader prefrontal/temporal cortex regions. Also notable in nervous system structures (cranial nerves, cerebellar regions).

Cell Type Expression (Bgee)

Cell type annotations from Bgee top conditions:

RankCell TypeExpression ScoreQuality
5Endothelial cell98.76Gold
11Monocyte98.59Gold
17Mononuclear cell98.25Gold

Note: Bgee integrates multiple cell type references. The data shows SNCA expression across immune cells (monocytes, mononuclear cells) and vascular endothelial cells, consistent with its neuroinflammatory role in Parkinson’s disease pathology.

Single-Cell Expression Datasets (SCXA)

SNCA is represented across 22 single-cell RNA-seq datasets in the Single Cell Expression Atlas:

Major dataset collections:

  • Hematopoiesis & immune: Census of Immune Cells (791K cells), fetal bone marrow (56K-56K cells), emerging haematopoiesis analysis
  • Fetal development: Fetal liver (197K-473K cells), fetal kidney (22K cells), embryonic kidney organoids
  • Neural development: Neural Plate Border Stem Cells, induced pluripotent stem cell-derived endothelial cells
  • Gastrointestinal: Spatially resolved single-cell atlas of human gastrointestinal tissue
  • Placental/reproductive: First-trimester placenta and decidua (41K cells)
  • Disease/specialized: COVID-19 blood, melanoma, chronic myelomonocytic leukemia, post-MI cardiac tissue

Notable representation: SNCA expression detected in immune cell surveys, neural progenitors, and fetal tissue development, supporting its role in both neural and innate immune homeostasis.

Disease associations

Mendelian / Monogenic Diseases

Autosomal Dominant Parkinson Diseases:

DiseaseDisease IDClassificationInheritanceEvidence
Parkinson diseaseMONDO:0005180DefinitiveAutosomal dominantAmbry Genetics
Autosomal dominant Parkinson disease 1 (ADPD1)OMIM:168601; MONDO:0008200StrongAutosomal dominantGenomics England PanelApp, Labcorp Genetics
Autosomal dominant Parkinson disease 4 (ADPD4)OMIM:605543; MONDO:0011562Definitive/StrongAutosomal dominantAmbry Genetics, Genomics England PanelApp, Labcorp Genetics
Lewy body dementiaOMIM:127750; MONDO:0007488StrongAutosomal dominantGenomics England PanelApp, Labcorp Genetics
Hereditary late-onset Parkinson diseaseOrphanet:411602SupportiveAutosomal dominantOrphanet
Young-onset Parkinson diseaseOrphanet:2828; MONDO:0017279—Autosomal dominantOrphanet

Autosomal Recessive:

DiseaseDisease IDClassificationInheritanceEvidence
Parkinsonian-pyramidal syndromeOrphanet:171695SupportiveAutosomal recessiveOrphanet

Phenotype Associations (HPO Terms) — Top 30

HPO TermHPO ID
Autosomal dominant inheritanceHP:0000006
Neurogenic bladderHP:0000011
Urinary urgencyHP:0000012
Hypomimic faceHP:0000338
Slow saccadic eye movementsHP:0000514
Color vision defectHP:0000551
DiplopiaHP:0000651
AgitationHP:0000713
DepressionHP:0000716
DementiaHP:0000726
Frontal lobe dementiaHP:0000727
Short attention spanHP:0000736
HallucinationsHP:0000738
AnxietyHP:0000739
ApathyHP:0000741
Low frustration toleranceHP:0000744
DelusionHP:0000746
SpasticityHP:0001257
DysarthriaHP:0001260
Mental deteriorationHP:0001268
Orthostatic hypotensionHP:0001278
Gait disturbanceHP:0001288
ParkinsonismHP:0001300
DystoniaHP:0001332
MyoclonusHP:0001336
TremorHP:0001337
HyperreflexiaHP:0001347
Talipes equinovarusHP:0001762
Weight lossHP:0001824
DiarrheaHP:0002014

Complex Disease / GWAS Associations — Top 30

Trait/DiseaseMapped GeneChromosomeP-valueGWAS Study
Parkinson’s diseaseSNCA42.00e-16GCST000528_4
Parkinson’s diseaseSNCA47.00e-17GCST000530_1
Parkinson’s diseaseSNCA47.00e-08GCST000567_6
Parkinson’s diseaseSNCA43.00e-11GCST000772_1
Parkinson’s diseaseSNCA49.00e-16GCST000855_3
Parkinson’s diseaseSNCA43.00e-08GCST000874_1
Parkinson’s diseaseSNCA42.00e-47GCST000959_7
Parkinson’s diseaseSNCA42.00e-19GCST001126_2
Parkinson’s diseaseSNCA48.00e-35GCST001430_2
Parkinson’s diseaseSNCA46.00e-65GCST001445_5
Parkinson’s diseaseSNCA-AS1, MMRN145.00e-11GCST001445_6
Parkinson’s diseaseSNCA41.00e-09GCST002353_2
Parkinson’s diseaseSNCA43.00e-11GCST002353_3
Parkinson’s diseaseSNCA44.00e-73GCST002544_19
Response to bupropion in depressionGPRIN3, SNCA43.00e-08GCST003800_1
Parkinson’s diseaseSNCA41.00e-32GCST003922_2
Parkinson’s diseaseSNCA41.00e-56GCST003984_5
Parkinson’s diseaseSNCA45.00e-123GCST004902_48
Dementia with Lewy bodiesSNCA49.00e-13GCST005276_2
Blood protein levelsSNCA48.00e-30GCST006585_2238
Blood protein levelsSNCA41.00e-09GCST006585_643
NeuroticismSNCA42.00e-10GCST006940_38
Feeling nervousSNCA41.00e-09GCST006948_44
Parkinson’s disease (age of onset)SNCA42.00e-12GCST007780_1
Parkinson’s disease (age of onset)SNCA-AS147.00e-06GCST007780_2
Emphysema annual change (adjusted lung density)SNCA47.00e-06GCST008477_24
PD or first-degree relation with PDSNCA44.00e-154GCST009325_4
PD or first-degree relation with PDSNCA41.00e-36GCST009325_5
PD or first-degree relation with PDGPRIN3, SNCA41.00e-48GCST009325_93
PD or first-degree relation with PDSNCA45.00e-149GCST009325_94

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 46 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gtex, gwas, hgnc, hpa, hpo, inparanoid, intact, interpro, jaspar, mim, mondo, msigdb, orphanet, ortholog, orthologentrez, pdb, pfam, pharmgkb_gene, reactome, refseq, scxa, spliceai, string, string_interaction, supfam, tabula, transcript, uniprot
Generated: 2026-05-26 — For the latest data, query BioBTree directly via MCP or API.
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