SNCA
synuclein alpha
Basic information
Region (hg38): 4:89700345-89838315
Previous symbols: [ "PARK1", "PARK4" ]
Links
Phenotypes
GenCC
Source:
- Lewy body dementia (Strong), mode of inheritance: AD
- autosomal dominant Parkinson disease 4 (Strong), mode of inheritance: AD
- autosomal dominant Parkinson disease 1 (Strong), mode of inheritance: AD
- autosomal dominant Parkinson disease 4 (Definitive), mode of inheritance: AD
- parkinsonian-pyramidal syndrome (Supportive), mode of inheritance: AR
- hereditary late onset Parkinson disease (Supportive), mode of inheritance: AD
- Lewy body dementia (Strong), mode of inheritance: AD
- autosomal dominant Parkinson disease 4 (Strong), mode of inheritance: AD
- Parkinson disease (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Parkinson disease 1; Parkinson disease 4; Dementia with Lewy bodies | AD | Neurologic | Levodopa can be beneficial in individuals with Parkinson disease | Neurologic | 2158268; 8285594; 9276199; 9197268; 11261505; 14593171; 14755720; 14755719; 16358335; 17251522; 18852448; 18413475; 18195271; 18852449; 18852445; 19139307; 19632874; 21412942; 21800132 |
ClinVar
This is a list of variants' phenotypes submitted to
- Lewy body dementia;Autosomal dominant Parkinson disease 1 (2 variants)
- Autosomal dominant Parkinson disease 1 (2 variants)
- Lewy body dementia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNCA gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 14 | ||||
| missense | 20 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 2 | 4 | 6 | |||
| non coding | 58 | 27 | 26 | 111 | ||
| Total | 3 | 2 | 79 | 44 | 26 |
Variants in SNCA
This is a list of pathogenic ClinVar variants found in the SNCA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-89724127-G-T | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89724232-C-T | Parkinson Disease, Dominant | Uncertain significance (Mar 23, 2018) | ||
| 4-89724298-G-A | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89724308-T-A | Parkinson Disease, Dominant | Likely benign (Jan 13, 2018) | ||
| 4-89724337-G-A | Parkinson Disease, Dominant | Likely benign (Jan 12, 2018) | ||
| 4-89724351-T-G | Parkinson Disease, Dominant | Likely benign (Jan 13, 2018) | ||
| 4-89724359-G-A | Parkinson Disease, Dominant | Uncertain significance (Jan 12, 2018) | ||
| 4-89724398-C-T | Parkinson Disease, Dominant | Benign (Jan 13, 2018) | ||
| 4-89724401-G-T | Parkinson Disease, Dominant | Likely benign (Jan 12, 2018) | ||
| 4-89724520-T-A | Parkinson Disease, Dominant | Benign (Jan 13, 2018) | ||
| 4-89724522-C-T | Parkinson Disease, Dominant | Likely benign (Jan 12, 2018) | ||
| 4-89724523-C-T | Parkinson Disease, Dominant | Benign (Jan 13, 2018) | ||
| 4-89724581-C-T | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89724591-A-G | Parkinson Disease, Dominant | Uncertain significance (Aug 01, 2021) | ||
| 4-89724645-T-C | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89724732-G-A | Parkinson Disease, Dominant | Benign (Jan 13, 2018) | ||
| 4-89724735-A-G | Parkinson Disease, Dominant | Uncertain significance (Jan 12, 2018) | ||
| 4-89724912-T-A | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89724926-C-T | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89724950-C-T | Parkinson Disease, Dominant | Uncertain significance (Jan 12, 2018) | ||
| 4-89724951-G-A | Parkinson Disease, Dominant | Benign (Jan 13, 2018) | ||
| 4-89725110-A-G | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89725303-T-C | Parkinson Disease, Dominant | Uncertain significance (Jan 13, 2018) | ||
| 4-89725316-TG-T | Parkinson Disease, Dominant | Uncertain significance (Jun 14, 2016) | ||
| 4-89725317-G-A | Parkinson Disease, Dominant | Uncertain significance (Jan 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SNCA | protein_coding | protein_coding | ENST00000394986 | 5 | 114217 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.883 | 0.116 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.460 | 61 | 72.0 | 0.847 | 0.00000331 | 896 |
| Missense in Polyphen | 16 | 31.898 | 0.50159 | 380 | ||
| Synonymous | -1.14 | 31 | 23.9 | 1.30 | 0.00000114 | 276 |
| Loss of Function | 2.45 | 0 | 6.98 | 0.00 | 2.99e-7 | 94 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.;
- Disease
- DISEASE: Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.; DISEASE: Parkinson disease 1, autosomal dominant (PARK1) [MIM:168601]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early- onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. {ECO:0000269|PubMed:14755719, ECO:0000269|PubMed:23427326, ECO:0000269|PubMed:23457019, ECO:0000269|PubMed:24936070, ECO:0000269|PubMed:25561023, ECO:0000269|PubMed:9197268, ECO:0000269|PubMed:9462735}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Parkinson disease 4, autosomal dominant (PARK4) [MIM:605543]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dementia Lewy body (DLB) [MIM:127750]: A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease. {ECO:0000269|PubMed:14755719}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Alzheimer,s disease - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Alzheimers Disease;Parkin-Ubiquitin Proteasomal System pathway;Parkinsons Disease Pathway;Ectoderm Differentiation;Metabolism of proteins;Amyloid fiber formation;alpha-synuclein and parkin-mediated proteolysis in parkinson`s disease;Alpha-synuclein signaling
(Consensus)
Recessive Scores
- pRec
- 0.416
Intolerance Scores
- loftool
- 0.105
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 42.88
Haploinsufficiency Scores
- pHI
- 0.725
- hipred
- Y
- hipred_score
- 0.826
- ghis
- 0.635
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.961
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Snca
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;microglial cell activation;positive regulation of receptor recycling;negative regulation of protein phosphorylation;positive regulation of neurotransmitter secretion;fatty acid metabolic process;neutral lipid metabolic process;phospholipid metabolic process;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;mitochondrial membrane organization;aging;adult locomotory behavior;response to iron(II) ion;regulation of phospholipase activity;negative regulation of platelet-derived growth factor receptor signaling pathway;regulation of glutamate secretion;regulation of dopamine secretion;regulation of transmembrane transporter activity;negative regulation of microtubule polymerization;receptor internalization;protein destabilization;response to magnesium ion;negative regulation of transporter activity;response to lipopolysaccharide;negative regulation of monooxygenase activity;positive regulation of peptidyl-serine phosphorylation;response to interferon-gamma;cellular response to oxidative stress;negative regulation of histone acetylation;regulation of locomotion;dopamine biosynthetic process;mitochondrial ATP synthesis coupled electron transport;regulation of macrophage activation;positive regulation of apoptotic process;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of neuron apoptotic process;cellular protein metabolic process;cellular response to fibroblast growth factor stimulus;positive regulation of endocytosis;negative regulation of exocytosis;negative regulation of dopamine metabolic process;behavioral response to cocaine;regulation of long-term neuronal synaptic plasticity;synaptic vesicle endocytosis;synaptic vesicle transport;positive regulation of inflammatory response;synapse organization;regulation of acyl-CoA biosynthetic process;positive regulation of release of sequestered calcium ion into cytosol;dopamine uptake involved in synaptic transmission;negative regulation of dopamine uptake involved in synaptic transmission;negative regulation of serotonin uptake;regulation of norepinephrine uptake;negative regulation of norepinephrine uptake;calcium ion homeostasis;oxidation-reduction process;excitatory postsynaptic potential;long-term synaptic potentiation;positive regulation of inositol phosphate biosynthetic process;negative regulation of thrombin-activated receptor signaling pathway;response to interleukin-1;cellular response to copper ion;cellular response to epinephrine stimulus;positive regulation of protein serine/threonine kinase activity;supramolecular fiber organization;negative regulation of neuron death;positive regulation of neuron death;negative regulation of mitochondrial electron transport, NADH to ubiquinone;positive regulation of glutathione peroxidase activity;positive regulation of hydrogen peroxide catabolic process;regulation of synaptic vesicle recycling;regulation of reactive oxygen species biosynthetic process;response to desipramine;negative regulation of chaperone-mediated autophagy;regulation of presynapse assembly
- Cellular component
- extracellular region;extracellular space;nucleus;nuclear outer membrane;cytoplasm;mitochondrion;mitochondrial outer membrane;mitochondrial respiratory chain complex I;mitochondrial intermembrane space;mitochondrial matrix;lysosome;rough endoplasmic reticulum;Golgi apparatus;cytosol;ribosome;plasma membrane;cell cortex;actin cytoskeleton;membrane;inclusion body;cell junction;axon;growth cone;synaptic vesicle membrane;platelet alpha granule membrane;neuronal cell body;terminal bouton;perinuclear region of cytoplasm;postsynapse;supramolecular fiber
- Molecular function
- magnesium ion binding;actin binding;fatty acid binding;copper ion binding;calcium ion binding;protein binding;phospholipid binding;microtubule binding;ferrous iron binding;zinc ion binding;oxidoreductase activity;kinesin binding;protein domain specific binding;Hsp70 protein binding;histone binding;identical protein binding;alpha-tubulin binding;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;phospholipase binding;transcription regulatory region DNA binding;protein N-terminus binding;tau protein binding;beta-tubulin binding;phosphoprotein binding;phospholipase D inhibitor activity;dynein complex binding;cuprous ion binding