SNCA (Synuclein Alpha) Gene
Genetic Insights into Parkinson's Disease and Synucleinopathies
Gene Information Card
| Symbol | SNCA |
|---|---|
| Full Name | Synuclein Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 4q22.1 |
| NCBI Gene ID | 6622 ncbi.nlm.nih.gov/gene/6622 |
| Ensembl ID | ENSG00000145335 |
| UniProt ID | P37840 |
| OMIM ID | 163890 |
| HGNC ID | 11138 |
| Aliases | NACP, PARK1, PARK4, PD1, alpha-synuclein |
Description
The SNCA gene encodes alpha-synuclein, a small presynaptic protein involved in synaptic vesicle trafficking and neurotransmitter release. Mutations and multiplications of SNCA are linked to familial and sporadic Parkinson's disease (PD) and other synucleinopathies. Aggregation of misfolded alpha-synuclein forms Lewy bodies, a hallmark of PD pathology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson's disease (PARK1/PARK4) | Gain-of-function: missense mutations (e.g., A53T, A30P) promote aggregation; gene duplications/triplications increase protein dosage, leading to Lewy body formation and dopaminergic neuron loss. | OMIM #168601, ClinVar, NCBI |
| Dementia with Lewy bodies (DLB) | Similar mechanism: alpha-synuclein aggregation in cortical and limbic regions. | OMIM #127750, ClinVar |
| Multiple system atrophy (MSA) | Alpha-synuclein accumulation in oligodendrocytes (glial cytoplasmic inclusions). | OMIM #146500, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 124.2 | High |
| Adrenal gland | 10.1 | Medium |
| Testis | 3.5 | Low |
| Heart | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal model, high expression |
| U-87 MG (glioblastoma) | 8.7 | Moderate expression |
| HEK 293 (embryonic kidney) | 2.1 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| A53T (c.157G>A) | Missense | Rare | Increased aggregation, early-onset PD |
| A30P (c.88G>C) | Missense | Rare | Reduced membrane binding, aggregation-prone |
| E46K (c.136G>A) | Missense | Rare | Enhanced fibril formation, PD/DLB |
| Gene duplication | Copy number gain | Rare | Dosage effect, early-onset PD |
| Gene triplication | Copy number gain | Very rare | Severe early-onset PD with dementia |
Mutation functional classification
Loss of Function (LOF)
Not established; SNCA knockout mice show mild synaptic defects but no neurodegeneration.
Gain of Function (GOF)
Missense mutations and multiplications increase alpha-synuclein aggregation and toxicity, leading to Lewy body pathology.
Dominant Negative (DN)
Not reported; mutations are primarily gain-of-function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0005737 – cytoplasm |
| • GO:0005886 – plasma membrane | • GO:0008021 – synaptic vesicle |
| • GO:0031982 – vesicle | • GO:0042803 – protein homodimerization activity |
| • GO:0045202 – synapse | • GO:0051082 – unfolded protein binding |
Pathways
• Parkinson's disease (KEGG: hsa05012)
• Synaptic vesicle cycle (KEGG: hsa04721)
• Alpha-synuclein signaling (Reactome: R-HSA-9623433)
Protein Summary
Alpha-synuclein is a 140-amino acid protein predominantly expressed in the brain, localized to presynaptic terminals. It is natively unfolded but can adopt alpha-helical structure upon membrane binding. Its physiological role involves synaptic vesicle clustering and dopamine homeostasis. Pathologically, misfolded alpha-synuclein aggregates into amyloid fibrils that constitute Lewy bodies, driving neurodegeneration in Parkinson's disease and related disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SNCA Knockout HEK293 Cell Line | EDJ-KQ954 | Human | 6622 | Details Get a Quote |
| SNCAIP Knockout HEK293 Cell Line | EDJ-KQ6664 | Human | 9627 | Details Get a Quote |
| SNCA Knockout HCT 116 Cell Line | EDJ-KQ19947 | Human | 6622 | Details Get a Quote |
| SNCA Knockout HeLa Cell Line | EDJ-KQ19948 | Human | 6622 | Details Get a Quote |
| SNCAIP Knockout HeLa Cell Line | EDJ-KQ30968 | Human | 9627 | Details Get a Quote |
| SNCA Knockout A-549 Cell Line | EDJ-KQ63015 | Human | 6622 | Details Get a Quote |
| SNCAIP Knockout A-549 Cell Line | EDJ-KQ63693 | Human | 9627 | Details Get a Quote |
| SNCAIP Knockout HCT 116 Cell Line | EDJ-KQ72155 | Human | 9627 | Details Get a Quote |
| SNCA Knockout H4 Cell Line | EDC07746 | Human | 6622 | Details Get a Quote |
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