SNCA

Chr 4AD

synuclein alpha

Also known as: NACP, PARK1, PARK4, PD1

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 presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Dementia, Lewy bodyMIM #127750
AD
Parkinson disease 1MIM #168601
AD
Parkinson disease 4MIM #605543
AD

Clinical highlights

Gene-disease validity (ClinGen)
Parkinson disease · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
8
Active trials
341
Pubs (1 yr)
P/LP submissions
P/LP missense
0.43
LOEUF
Multiple*
Mechanism· predicted
📖
GeneReview available — SNCA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.43LOEUF
pLI 0.883
Z-score 2.45
OE 0.00 (0.000.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.46Z-score
OE missense 0.85 (0.691.05)
61 obs / 72.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.000.43)
00.351.4
Missense OE?0.85 (0.691.05)
00.61.4
Synonymous OE?1.30
01.21.6
LoF obs/exp: 0 / 7.0Missense obs/exp: 61 / 72.0Syn Z: -1.14

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SNCA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Parkinson'sParkinson DiseaseParkinson's Disease

Longitudinal Investigation of I2BS in PD

RECRUITING
NCT05516719University of ExeterStarted 2021-11-01
Positron Emission Tomography (PET) scan using BU99008 tracerFP-CIT Single-photon Emission Computed Tomography (SPECT) scanMagnetic Resonance Imaging (MRI) Scan
Restless Leg Syndrome (RLS)

Observe Change in Nasal Swab DRD2 Gene Expression in Restless Legs Syndrome (RLS) Patients on Prolonged Dopamine Agonist Treatment

RECRUITING
NCT06726785HBC Immunology IncStarted 2025-07-01
Parkinson Disease

Chinese PD-SNCA Registry

RECRUITING
NCT03523052Xiangya Hospital of Central South UniversityStarted 2017-02-01
Parkinson's Disease (PD)

Safety, Tolerability and Exploratory Efficacy of EC5026 in Parkinson's Disease (STEP Study)

RECRUITING
NCT07142044Phase PHASE1, PHASE2EicOsis Human Health Inc.Started 2025-11-01
EC5026 oral tabletPlacebo
Parkinson DiseaseNervous System DisorderNeurodegenerative Diseases

Molecular and Functional Imaging in Monogenic PD.

RECRUITING
NCT05518617University of ExeterStarted 2022-07-01
Positron Emission Tomography (PET) scan using DASB tracer
Young Onset Parkinson DiseaseParkinson Disease

Young Onset Parkinson's Disease Subtypes and Pathogenic Mechanisms

RECRUITING
NCT07752355NYU Langone HealthStarted 2024-02-28
Parkinson DiseaseParkinson'sParkinson's Disease

Serotonin Release in Premotor and Motor PD

RECRUITING
NCT05516732University of ExeterStarted 2022-07-01
Positron Emission Tomography (PET) scan using CIMBI-36 tracerMagnetic Resonance Imaging (MRI) ScanPositron Emission Tomography (PET) scan using DASB tracer
Parkinson's Disease (PD)GBA1 Parkinson DiseaseREM Sleep Behavior Disorder (iRBD)

Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging

NOT YET RECRUITING
NCT07474779Phase NAUniversity of PaviaStarted 2026-05-11
brain imagingblood drawSkin biopsy