Seroatlas · Human Serome Atlas

SNCA

Alpha-synuclein

Also known as: NACP, PARK1, PARK4, PD1, SYUA_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P37840
Gene
SNCA
Ensembl
ENSG00000145335
Chromosome
4
Canonical length
140 aa
Protein class
Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters
Secretome location
Intracellular and membrane
Quaternary structure
Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

140 residues, UniProt reviewed canonical sequence.

>P37840|SNCA
     1  MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK
    61  EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL GKNEEGAPQE GILEDMPVDP
   121  DNEAYEMPSE EGYQDYEPEA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SNCA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.57
Highest tissue expression
263 nTPM

Expression across tissuesHPA

Tissue

  • cerebral cortex: 263 nTPM
  • bone marrow: 258 nTPM
  • cerebellum: 168 nTPM
  • amygdala: 157 nTPM
  • midbrain: 142 nTPM
  • hippocampal formation: 137 nTPM

Single-cell type

  • megakaryocytes: 1,366 nCPM
  • platelets: 1,211 nCPM
  • erythrocytes: 921 nCPM
  • melanocytes: 876 nCPM
  • erythrocyte progenitors: 322 nCPM
  • brain excitatory neurons: 254 nCPM

Immune cell

  • plasmacytoid DC: 103 nTPM
  • myeloid DC: 85 nTPM
  • classical monocyte: 67 nTPM
  • total PBMC: 64 nTPM
  • basophil: 52 nTPM
  • intermediate monocyte: 28 nTPM

Brain region

  • cerebral cortex: 239 nTPM
  • basal ganglia: 228 nTPM
  • white matter: 218 nTPM
  • pons: 204 nTPM
  • midbrain: 191 nTPM
  • hippocampal formation: 166 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SNCA.

Disease | AllUniProt

Conditions SNCA is implicated in, by any mechanism.

  • Parkinson disease 1, autosomal dominant (PARK1) MIM:168601
  • Parkinson disease 4, autosomal dominant (PARK4) MIM:605543
  • Dementia, Lewy body (DLB) MIM:127750

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 173 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Autosomal dominant Parkinson disease 1
  • Lewy body dementia
  • Autosomal dominant Parkinson disease 4

Disease | ImmuneIEDB

Conditions an epitope on SNCA was assayed in.

Disease | AutoantibodyPubMed

Conditions in which antibodies against SNCA are reported. Each links to that disease's full target list.

Showing 6 of 9 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for SNCA from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

49 publications

Show 20 more of 49 total

Reference: B cellIEDB

5 publications

Reference: T cellIEDB

3 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.43
gnomAD pLI
0.88
gnomAD missense Z
0.46
DepMap mean gene effect
0.12
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SNCA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SNCA as an antibody target. Whether an autoantibody or antibody against SNCA could matter depends on whether native SNCA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SNCA is annotated as secreted, so native SNCA circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label SNCA as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SNCA. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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