Protein / target

Alpha-synuclein

Encoded bySNCAP37840Homo sapiensSwiss-Prot

UniProt: P37840 Ensembl: ENSG00000145335 HGNC: HGNC:11138 NCBI Gene: 6622

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Cysteine-type endopeptidase inhibitor

Strongest disease association

Parkinson's Disease

Via encoding gene SNCA · Genetic evidence · score 0.86

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Actively researched

36 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release.

View complete UniProt function annotation

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 monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Also acts as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590)

Subcellular location

CytoplasmMembraneNucleusSynapseSecretedCell projection, axon

Domains and Gene Ontology detail (115)

Gene Ontology

Cactin cytoskeleton
Caxon
Caxon terminus
Ccell cortex
Ccytoplasm
Ccytosol
Cextracellular region
Cextracellular space
Cgrowth cone
Cinclusion body
CLewy body
Clysosome

140 aa · 14 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GOGrowth-factor signallingGOMetabolic enzyme activityGOApoptosis & cell deathGOImmune signallingGOTranscriptional regulationGO

View supporting evidence

Synaptic signalling

·Neuronal protein that plays several roles in synaptic activity such as regulation of syn…
·Synapse
·dopamine uptake involved in synaptic transmission
·negative regulation of dopamine uptake involved in synaptic transmission

Growth-factor signalling

·cellular response to fibroblast growth factor stimulus
·negative regulation of platelet-derived growth factor receptor signaling pathway

Metabolic enzyme activity

·oxidoreductase activity
·glutathione metabolic process
·negative regulation of dopamine metabolic process

Apoptosis & cell death

·negative regulation of apoptotic process
·negative regulation of neuron apoptotic process
·positive regulation of apoptotic process

Immune signalling

·positive regulation of inflammatory response
·response to interleukin-1

Transcriptional regulation

·transcription cis-regulatory region binding
·negative regulation of transcription by RNA polymerase II

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SNCA

Gene-level evidence surfaced through the gene SNCAthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Parkinson's Disease

0.92Well supported

Genetic evidence dominant · Open Targets 0.71

Lewy Body Disease

0.87Well supported

Genetic evidence dominant · Open Targets 0.74

Sleep Initiation and Maintenance Disorders

0.63Moderately supported

Genetic evidence dominant · Open Targets 0.39

REM Sleep Behavior Disorder

0.63Moderately supported

Genetic evidence dominant · Open Targets 0.38

Immunoglobulin Light-chain Amyloidosis

0.30Preliminary

Pathway evidence dominant · Open Targets 0.46 · no direct causal or clinical evidence

View evidence synthesis (5)

Parkinson's DiseaseWell supported

0.92

agreement 0.82–1.00

Genetic62%Clinical27%Literature11%RNA expression1%Genetic literaturedup

Open Targets aggregate 0.71 · 4 independent evidence families · 1 not counted as duplicate

Lewy Body DiseaseWell supported

0.87

agreement 0.75–0.99

Genetic72%Animal model15%Literature13%Genetic literaturedup

Open Targets aggregate 0.74 · 3 independent evidence families · 1 not counted as duplicate

Sleep Initiation and Maintenance DisordersModerately supported

0.63

agreement 0.49–0.77

Genetic98%Literature2%

Open Targets aggregate 0.39 · 2 independent evidence families

REM Sleep Behavior DisorderModerately supported

0.63

agreement 0.49–0.77

Genetic93%Literature7%

Open Targets aggregate 0.38 · 2 independent evidence families

Immunoglobulin Light-chain AmyloidosisPreliminary

0.30

agreement 0.08–0.53

Pathway100%

Open Targets aggregate 0.46 · 1 independent evidence family · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Lewy Body Disease0.74

Parkinson's Disease0.71

Immunoglobulin Light-chain Amyloidosis0.46

Sleep Initiation and Maintenance Disorders0.39

REM Sleep Behavior Disorder0.38

Drug development

2 compounds recorded · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (2)

PRASINEZUMABPhase 3

CINPANEMABPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Strong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)

SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.