Human Gene Module / Chromosome 3 / SYN2

SYN2Synapsin II

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
5 / 0
Aliases
SYN2, SYNII,  SYNIIa,  SYNIIb
Associated Syndromes
-
Chromosome Band
3p25.2
Associated Disorders
EPS
Relevance to Autism

Maternally-inherited frameshift (A94fs199X) and missense (Y236S and G464R) variants in SYN2 were found to be associated with ASD in male cases (Corradi et al., 2013). Deletion of SYN2 in mice extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming (Greco et al., 2013).

Molecular Function

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. This member of the synapsin family encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Mutations in this gene may be associated with abnormal presynaptic function and schizophrenia.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
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Mouse
Entrez Gene
SFARI Genomic Platforms
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Reports related to SYN2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia Lee HJ , et al. (2005) No -
2 Positive Association Association of synapsin 2 with schizophrenia in families of Northern European ancestry Saviouk V , et al. (2007) No -
3 Recent Recommendation Autism-related behavioral abnormalities in synapsin knockout mice Greco B , et al. (2013) Yes -
4 Primary SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth Corradi A , et al. (2013) Yes Epilepsy
5 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
6 Recent Recommendation Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype Feliciano P , et al. (2017) No -
7 Support - Bckstrm F et al. (2023) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.707A>C p.Tyr236Ser missense_variant Familial Maternal Simplex 23956174 Corradi A , et al. (2013)
c.757C>G p.Pro253Ala missense_variant Familial Maternal Unknown 23956174 Corradi A , et al. (2013)
c.1390G>C p.Asp464His missense_variant Familial Maternal Simplex 23956174 Corradi A , et al. (2013)
c.282_288del p.Ala95LeufsTer105 frameshift_variant Familial Maternal Simplex 23956174 Corradi A , et al. (2013)
c.557G>A p.Arg186Gln missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Maternally-inherited frameshift and missense variants in SYN2 were found to be associated with ASD in male cases in Corradi et al., 2013; both missense variants were unable to rescue presynaptic phenotypes in SYN2 knockout neurons. Deletion of SYN2 in mice extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming (Greco et al., 2013).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Maternally-inherited frameshift and missense variants in SYN2 were found to be associated with ASD in male cases in Corradi et al., 2013; both missense variants were unable to rescue presynaptic phenotypes in SYN2 knockout neurons. Deletion of SYN2 in mice extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming (Greco et al., 2013).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Maternally-inherited frameshift and missense variants in SYN2 were found to be associated with ASD in male cases in Corradi et al., 2013; both missense variants were unable to rescue presynaptic phenotypes in SYN2 knockout neurons. Deletion of SYN2 in mice extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming (Greco et al., 2013).

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

Maternally-inherited frameshift and missense variants in SYN2 were found to be associated with ASD in male cases in Corradi et al., 2013; both missense variants were unable to rescue presynaptic phenotypes in SYN2 knockout neurons. Deletion of SYN2 in mice extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming (Greco et al., 2013).

Krishnan Probability Score

Score 0.76620886475618

Ranking 7/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
Sanders TADA Score

Score 0.83903481561454

Ranking 3104/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 17

Ranking 120/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.45233085602013

Ranking 898/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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