SNCB

protein-coding

synuclein beta, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a member of a small family of proteins that inhibit phospholipase D2 and may function in neuronal plasticity. The encoded protein is abundant in lesions of patients with Alzheimer disease. A mutation in this gene was found in individuals with dementia with Lewy bodies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MANE transcript

NM_003085.5

Inheritance

ClinVar variants

P:2U:12B:1

Top phenotype

Dementia with Lewy bodies

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr5:176,620,082-176,630,556

External References & Databases

Ensembl (ENSG00000074317)

Transcript & Mutation Effects

hg38 • Region Span ~10.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Lewy body dementiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007488

Submitter: Ambry Genetics

Lewy body dementiaMODERATE

Inheritance Pattern: Unknown

Disease ID:MONDO:0007488

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Dementia with Lewy bodiesAD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 15365127

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SNCB variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 9

Lewy body dementiaTotal: 6

not providedTotal: 2

SNCB-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003085.5. 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				1 clinvar		1
missense	1 clinvar	1 clinvar	11 clinvar			13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	1	12	1	0	15

Highest pathogenic variant AF is 0.00028099192

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003085.5	RefSeq	NP_003076.1	5	MANE Select
ENST00000393693.7	Ensembl	ENSP00000377296.2	5	MANE Select
NM_001001502.3	RefSeq	NP_001001502.1	5	Standard
NM_001318034.2	RefSeq	NP_001304963.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sncb	Danio rerio	Structure: larval locomotory behavior Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

sncb

Danio rerio

Structure: larval locomotory behavior

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MTF1 activates gene expression
MTF1 activates gene expression
Response to metal ions
Cellular responses to external stimuli

Biological Process

chemical synaptic transmission
response to metal ion
dopamine metabolic process
negative regulation of catalytic activity
negative regulation of neuron apoptotic process

Molecular Function

phospholipase inhibitor activity
calcium ion binding
transition metal ion binding
cuprous ion binding

Cellular Component

cytosol
inclusion body
presynapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310112
Coding exons: 5
Length: 10446
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.952	50	72.9	0.686	0.00000332	853
Missense (PolyPhen)		12	19.075	0.62911		214
Synonymous	-0.279	31	29.1	1.07	0.00000143	262
Loss of Function	1.63	3	7.94	0.378	3.93e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated caspase activation in a p53/TP53- dependent manner. Contributes to restore the SNCA anti-apoptotic function abolished by 6OHDA. Not found in the Lewy bodies associated with Parkinson disease.;

Recessive Scores

pRec: 0.221

Intolerance Scores

LoFtool: 0.375
RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.637

Gene Damage Prediction

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