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Symbol SNCA contributors: mct - updated : 20-08-2017
HGNC name synuclein, alpha (non A4 component of amyloid precursor)
HGNC id 11138
Corresponding disease
PARK1 Parkinson disease, 1
Location 4q22.1      Physical location : 90.645.250 - 90.759.447
Synonym name
  • non A-beta component of AD amyloid
  • alpha-synuclein
  • Synonym symbol(s) NACP, PD1, PARK1, PARK4, NACP112, NACP140, aSYN
    TYPE functioning gene
    STRUCTURE 111.43 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    motif repetitive sequence
    text structure three sp1 binding sites, polymorphic NACP-Rep1 elements modulating the activity of SNCA promoter/enhancer
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 3215 14.46 140 - 2014 2462967
  • containing exons 2a & 6a (longer than 2b & 6b respectively)
  • encoding for the longest isoform
  • also called NACP140
  • 4 splicing 3211 14.46 140 fetal and adult brain (highly) and skeletal muscle, pancreas, not in liver 2014 2462967
  • containing exons 2b et 6b (shorter than 2a et 6a respectively)
  • lacking exons 1 & 5
  • also called NACP112
  • 5 splicing 3022 14.46 140 ubiquination by Parkin in the brain 2014 2462967
  • lacking exon 3
  • encoding for a soluble ant glycosylated isoform
  • also called ASP22
  • 4 - 3127 - 112 - 2014 2462967
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
    Endocrinepancreas   moderately
    Nervousbrain   highly
     nerve   highly
    Skin/Tegumentskin   moderately
    Urinarybladder   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines highly in ovarian and breast carcinomas
    at STAGE
    physiological period fetal
    Text brain
  • seven imperfect repeats of 11 aminoacids with the consensus core KTKEGV, homolog to 14-3-3 proteins YWHAs
  • a twelve amino-acids stretch in the hydrophobic domain essential for filament assembly
  • C-terminal peptide with a second acidic repat important for the chaperone activity
  • conjugated ubiquitinated
    interspecies homolog to rattus Snca (95.00 pc)
    homolog to murine Snca (95.00 pc)
  • synuclein family
  • CATEGORY chaperone/stress
        plasma membrane
  • concentrated in presynaptic nerve terminals
  • mitochondrial translocation is promoted by intracellular acidification
  • basic FUNCTION
  • involved in exocytosis of synaptic vesicles, in synapse maintenance and plasticity
  • induction of mitochondrial dysfunction and oxidative stress
  • contributing to cell death in neurodegenerative diseases and accumulating in dentritic neurites and in Lewy bodies (neuronal and oligoendrocytic aggregates)
  • regulating vesicles recycling via its inhibition of PLD2 and/or its ability to bind fatty acids
  • playing a vital role in the modulation of dopamine transporter (DAT) function
  • negative regulator of synaptic vesicle priming before fusion, that causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive
  • direct role in mitochondrial physiology, especially under pathological conditions, and in principle, link SNCA to other Parkinson disease genes in regulating mitochondrial homeostasis
  • likely SNCA protein levels hardly affect mitochondrial morphology in normal cell lines, but may have some influence on that under certain environmental conditions
  • may modulate neurite outgrowth by interacting with the cytoskeletal protein SPTBN1
  • soluble SNCA is a novel modulator of Alzheimer disease pathophysiology
  • role of SNCA in adult hippocampal neurogenesis
  • is normally secreted from neuronal cells and can thus exert paracrine effects
  • is potentially able to reduce iron using copper as its catalytic centre
  • tight link between the intracellular level of SNCA and maturation capacity of primary oligodendrocyte progenitor cells
  • because both SNCA and CPLX1 modulate vesicle release, likely presynaptic dysfunction is an early event in Parkinson disease pathology
  • promotes SNARE complex assembly at the presynaptic plasma membrane in its multimeric membrane-bound state, but not in its monomeric cytosolic state
  • is transported into and out of the brain by the blood-brain barrier
  • is shown to cause mitochondrial impairment through interaction with permeability transition pore complex
  • extracellular SNCA alters synaptic transmission in brain neurons by perforating the neuronal plasma membrane
  • TPPP and SNCA have two key features: they are disordered and co-enriched/co-localized in brain inclusions
    a component
  • non A/beta constituent of Alzheimer amyloid precursor alpha
    small molecule
  • role for iron in the translational control of SNCA expression, suggesting that iron chelation may be a valid approach to control SNCA levels in the brain
  • protein
  • synphilin 1 (SNCAIP) binding
  • associating with PRKC and other proteins
  • binding to 14-3-3 (YWAHs) and acting as a potential chaperone with UBCH7 (isoform ASP22)
  • disrupts cellular Rab homeostasis
  • the specific interaction between SNCA and SNCAIP provides mechanistic insights into the inclusion-body formation in cells and pathological implication in Parkinson disease
  • binds TRAF6 that enhances its ubiquitination with atypical chains (possibility that SNCA might be an additional Parkinson disease-associated target of TRAF6 ligase activity)
  • SNCA modulates vesicle trafficking through its interaction with RABAC1
  • protects the integrity of PLCB1 and its ability to be activated by Galpha(q), which may in turn impact Ca2+ signaling
  • likely modulates neurite outgrowth by interacting with cytoskeletal proteins such as SPTBN1
  • is a substrate of PLK2, and elevated levels of SNCA prevent PLK2 from maintaining a normal level of GTP-bound RHO1, which is an essential GTPase that regulates stress signaling
  • TOMM40 mediates mitochondrial dysfunction induced by SNCA accumulation in Parkinson disease
  • TPPP lowered the mobility of autophagosomes and hindered the final maturation of autophagosomes by preventing their fusion with lysosomes for the final degradation of SNCA
  • its overexpression may promote SRC activation and PPP2R4 inactivation, leading to hyperphosphorylation of proteins, and may lead to neurodegeneration in PD in part by suppressing the endogenous neuroprotective activity of PPP2R4
  • SNCA interacts with GBA and efficiently inhibits enzyme activity
  • PSAP a protein vital for GBA activity, protects GBA against SNCA inhibition
  • ZSCAN21 expression decreases SNCA aggregation in the cells
  • ENDOG is a critical downstream executor of SNCA cytotoxicity
  • critical regulatory role for that endogenous CTSD activity in dopaminergic cells in SNCA homeostasis which cannot be compensated for by increased CTSB
  • FOXO3 is an important determinant of neuronal survival in the substantia nigra, which may oppose SNCA accumulation and proteotoxicity
  • PARK2 ubiquitination affects its protein stability and E3 ligase activity, possibly leading to SNCA sequestration and subsequent clearance
  • interactions between VPS35, EIF4G1, and SNCA
  • upon interacting with SNCA, HSPA5 activates a signaling cascade leading to cofilin 1 inactivation and stabilization of microfilaments
  • ZSCAN21 plays an important regulatory role in SNCA transcription
  • endolysosomal protein ATP13A2 can determine the fate of alpha-synuclein (SNCA)
  • TRIM32 binds to the promoter region of SNCA, suggesting a novel mechanism of its transcriptional regulation
  • DNAJB6 and HSPA4 cooperate to suppress SNCA aggregation
  • RER1 is a novel and potential important mediator of elevated SNCA levels
  • TRIM17 and TRIM41 modulate SNCA expression by regulating ZSCAN21
  • cell & other
    Phosphorylated by PTPN1 (phosphorylation of SNCA is crucial in compensating for proteasomal dysfunction)
    Other regulated by PARP1(binding to NACP-Rep1)
    phosphorylated by PLK2 in neurons (Inglis, 2009)
    its monoubiquitylation by SIAH is decreased by SNCAIP
    NEDD4 overexpression enhances SNCA ubiquitination and clearance by a lysosomal process requiring components of the endosomal-sorting complex required for transport
    corresponding disease(s) PARK1
    related resource Alpha - Synuclein Locus Mutation Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   amplification    
    triplicated locus in Parkinson 4 (PARK4)
  • to sporadic Parkinson disease (PD)
  • to variability of age at onset of Parkinson's disease
  • Variant & Polymorphism SNP
  • "protective" genotype 259/259 of the PD-associated promoter repeat NACP-Rep1 is associated with lower protein levels in blood
  • rs356219 risk allele in the SNCA gene significantly contributing to earlier age at onset
  • Candidate gene
  • increased SNCA and altered phagocytosis may provide a useful biomarker for human Parkinson disease
  • Therapy target
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    secreted SNCA exerts toxicity through engagement, at least in part, of the Ca2+ homeostatic machinery, and therefore, manipulating Ca2+ signaling pathways might represent a potential therapeutic strategy for Parkinson disease