SNCAIP

protein-coding

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

Gene summary

This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MANE transcript

NM_005460.4

Inheritance

ClinVar variants

U:133B:43

Top phenotype

Parkinson disease

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr5:122,311,354-122,464,219

External References & Databases

Ensembl (ENSG00000064692)

Transcript & Mutation Effects

hg38 • Region Span ~152.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Parkinson diseaseAD

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Levodopa can be beneficial in individuals with Parkinson disease

Comments: The pathogenicity of reported variants is unclear

Refs: 12761037; 18366718

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SNCAIP variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 120

Parkinson Disease, Dominant/RecessiveTotal: 52

not providedTotal: 30

Parkinson disease, late-onsetTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005460.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	24 clinvar	4 clinvar	41
missense			116 clinvar	13 clinvar	2 clinvar	131
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	133	37	6	176

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 114 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005460.4	RefSeq	NP_005451.2	10	MANE Select
ENST00000261368.13	Ensembl	ENSP00000261368.8	10	MANE Select
NM_001242935.3	RefSeq	NP_001229864.1	9	Standard
NM_001308100.2	RefSeq	NP_001295029.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Parkinson,s disease - Homo sapiens (human)
Parkin-Ubiquitin Proteasomal System pathway
Parkinsons Disease Pathway
Metabolism of proteins
Amyloid fiber formation

Biological Process

cell death
dopamine metabolic process
cellular protein metabolic process
regulation of neurotransmitter secretion
regulation of inclusion body assembly

Molecular Function

protein binding
ubiquitin protein ligase binding
identical protein binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
synaptic vesicle
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261368
Coding exons: 10
Length: 152866
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125747
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.766	438	485	0.902	0.0000267	6005
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.171

Intolerance Scores

LoFtool: 0.670
RVIS EVS: 0.23
RVIS percentile EVS: 68.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.720

Gene Damage Prediction

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