SNCAIP

synuclein alpha interacting protein, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 5:122311353-122464219

Links

ENSG00000064692 ∙ NCBI:9627 ∙ OMIM:603779 ∙ HGNC:11139 ∙ Uniprot:Q9Y6H5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease	AD	Neurologic	Levodopa can be beneficial in individuals with Parkinson disease	Neurologic	12761037; 18366718
The pathogenicity of reported variants is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNCAIP gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNCAIP 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	16	8	34
missense			67	12	2	81
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			5		1	6
non coding			11	5	1	17
Total	0	0	89	33	11

Variants in SNCAIP

This is a list of pathogenic ClinVar variants found in the SNCAIP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-122312265-C-T		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 13, 2018)
5-122312277-C-A		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 12, 2018)
5-122312282-C-G		Parkinson Disease, Dominant/Recessive	Benign (Jan 12, 2018)
5-122312283-G-A		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 12, 2018)
5-122312287-G-A		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 13, 2018)
5-122391083-G-A		Parkinson Disease, Dominant/Recessive	Uncertain significance (Apr 27, 2017)
5-122391109-G-A		Parkinson Disease, Dominant/Recessive	Likely benign (Jan 12, 2018)
5-122391122-G-T		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 12, 2018)
5-122391178-G-A		not specified	Uncertain significance (May 03, 2023)
5-122403816-G-A		Parkinson Disease, Dominant/Recessive	Benign (Dec 31, 2019)
5-122403833-G-A		not specified	Uncertain significance (Jun 11, 2021)
5-122403845-C-T		not specified	Uncertain significance (Jan 06, 2023)
5-122403846-G-A		Parkinson Disease, Dominant/Recessive	Likely benign (Jun 01, 2022)
5-122403857-A-G		not specified	Uncertain significance (Jan 24, 2024)
5-122422874-G-A		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 12, 2018)
5-122422887-T-A		not specified	Uncertain significance (Feb 13, 2024)
5-122422894-A-G		not specified	Likely benign (Mar 01, 2024)
5-122422927-A-T		not specified	Uncertain significance (Jun 05, 2023)
5-122422935-C-T		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 12, 2018)
5-122422941-T-C		Parkinson Disease, Dominant/Recessive	Uncertain significance (Jan 12, 2018)
5-122422954-T-C			Likely benign (Feb 13, 2018)
5-122422977-G-A			Likely benign (Jun 08, 2018)
5-122422995-A-G		Parkinson Disease, Dominant/Recessive	Likely benign (Jan 12, 2018)
5-122422998-G-T		not specified	Uncertain significance (May 03, 2023)
5-122423009-A-G		not specified	Uncertain significance (Sep 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNCAIP	protein_coding	protein_coding	ENST00000261368	10	152866

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000328	1.00	125723	0	24	125747	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.766	438	485	0.902	0.0000267	6005
Missense in Polyphen		164	208.32	0.78723		2592
Synonymous	0.249	193	197	0.977	0.0000120	1819
Loss of Function	3.70	13	37.4	0.347	0.00000184	473

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000367	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000796	0.0000791
Middle Eastern	0.000163	0.000163
South Asian	0.0000981	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1. {ECO:0000269|PubMed:16595633, ECO:0000269|PubMed:19224863}.
• Disease: DISEASE: Parkinson disease (PARK) [MIM:168600]: 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:12761037}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• Pathway: Parkinson,s disease - Homo sapiens (human);Parkin-Ubiquitin Proteasomal System pathway;Parkinsons Disease Pathway;Metabolism of proteins;Amyloid fiber formation;Alpha-synuclein signaling (Consensus)

Recessive Scores

• pRec: 0.171

Intolerance Scores

• loftool: 0.670
• rvis_EVS: 0.23
• rvis_percentile_EVS: 68.54

Haploinsufficiency Scores

• pHI: 0.270
• hipred: Y
• hipred_score: 0.747
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.720

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sncaip

Gene ontology

• Biological process: cell death;dopamine metabolic process;cellular protein metabolic process;regulation of neurotransmitter secretion;regulation of inclusion body assembly
• Cellular component: nucleoplasm;cytoplasm;cytosol;synaptic vesicle;cytoplasmic ribonucleoprotein granule;presynaptic membrane;neuronal cell body
• Molecular function: protein binding;ubiquitin protein ligase binding;identical protein binding