SYN3

protein-coding

synapsin III, the group of Synapsins

Gene summary

This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

MANE transcript

NM_003490.4

Inheritance

—

ClinVar variants

P:1U:79B:14

Top phenotype

Sorsby fundus dystrophy

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr22:32,507,820-33,058,381

External References & Databases

Ensembl (ENSG00000185666)

Transcript & Mutation Effects

hg38 • Region Span ~550.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYN3 variants in ClinVar

13 Conditions Cataloged

not providedTotal: 170

Sorsby fundus dystrophyTotal: 105

not specifiedTotal: 100

Retinal dystrophyTotal: 13

TIMP3-related disorderTotal: 5

Retinal disorderTotal: 2

Generalized hypotoniaTotal: 1

Visual impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003490.4. 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				2 clinvar	2 clinvar	4
missense	1 clinvar		76 clinvar	8 clinvar	2 clinvar	87
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	79	10	4	94

Highest pathogenic variant AF is 0.0000025271638

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003490.4	RefSeq	NP_003481.3	13	MANE Select
ENST00000358763.7	Ensembl	ENSP00000351614.2	13	MANE Select
NM_001135774.2	RefSeq	NP_001129246.1	13	Standard
NM_001369907.1	RefSeq	NP_001356836.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Synaptic Vesicle Pathway
Neuronal System
Dopamine Neurotransmitter Release Cycle
Neurotransmitter release cycle
Transmission across Chemical Synapses

Biological Process

neurotransmitter secretion
regulation of synaptic transmission, GABAergic
synaptic vesicle clustering

Molecular Function

ATP binding

Cellular Component

synaptic vesicle
postsynaptic density
cell junction
synaptic vesicle membrane
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358763
Coding exons: 13
Length: 545820
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	289	343	0.842	0.0000197	3774
Missense (PolyPhen)		37	41.224	0.89754		429
Synonymous	1.96	113	143	0.792	0.00000877	1172
Loss of Function	3.26	10	28.9	0.346	0.00000140	312

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00013	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00046	0.00042	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in the regulation of neurotransmitter release and synaptogenesis.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.147
RVIS EVS: -0.24
RVIS percentile EVS: 36.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.929

Gene Damage Prediction

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