SNCA

synuclein alpha

Basic information

Region (hg38): 4:89700344-89838315

Previous symbols: [ "PARK1", "PARK4" ]

Links

ENSG00000145335 ∙ NCBI:6622 ∙ OMIM:163890 ∙ HGNC:11138 ∙ Uniprot:P37840 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the SNCA gene.

• Parkinson Disease, Dominant (93 variants)
• not provided (38 variants)
• Lewy body dementia;Autosomal dominant Parkinson disease 1 (28 variants)
• Autosomal dominant Parkinson disease 1;Lewy body dementia (10 variants)
• Autosomal dominant Parkinson disease 1 (8 variants)
• Autosomal dominant Parkinson disease 4;Lewy body dementia;Autosomal dominant Parkinson disease 1 (4 variants)
• Autosomal dominant Parkinson disease 1;Lewy body dementia;Autosomal dominant Parkinson disease 4 (2 variants)
• Lewy body dementia;Autosomal dominant Parkinson disease 1;Autosomal dominant Parkinson disease 4 (1 variants)
• Lewy body dementia;Autosomal dominant Parkinson disease 4;Autosomal dominant Parkinson disease 1 (1 variants)
• Lewy body dementia (1 variants)
• Inborn genetic diseases (1 variants)
• Autosomal dominant Parkinson disease 4 (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				10		10
missense	3	2	17	1	1	24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	3		5
non coding			58	24	26	108
Total	3	2	76	35	27

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: gnomAD

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: dbNSFP

• 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