Human Gene Module / Chromosome 20 / SNAP25

SNAP25Synaptosomal-associated protein, 25kDa

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
2 / 3
Aliases
SNAP25, RIC-4,  RIC4,  SEC9,  SNAP, SNAP-25,  bA416N4.2,  dJ1068F16.2
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
20p12.2
Associated Disorders
DD/NDD, ID
Relevance to Autism

SNAP25+/- mice exhibit hyperactivity, cognitive and social impairment (Braida et al., 2015). In this same report, a SNP encompassing a regulatory element of SNAP25 (rs363050) was shown to associate with both CARS scores (p=0.005) and cognitive scores (p=0.003) in an ASD cohort, while a SNP within intron 1 of the SNAP25 gene (rs363043) had previously been shown to associate with both increasing CARS (p=0.001) and hyperactivity scores (p=0.006) in a separate ASD cohort (Guerini et al., 2011).

Molecular Function

This gene encodes a t-SNARE involved in the molecular regulation of neurotransmitter release that associates with proteins involved in vesicle docking and membrane fusion and may play an important role in the synaptic function of specific neuronal systems. Polymorphisms in this gene have been shown to associate with ADHD.

Reports related to SNAP25 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association SNAP-25 single nucleotide polymorphisms are associated with hyperactivity in autism spectrum disorders. Guerini FR , et al. (2011) Yes -
2 Primary Association between SNAP-25 gene polymorphisms and cognition in autism: functional consequences and potential therapeutic strategies. Braida D , et al. (2015) Yes -
3 Recent Recommendation Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis. Fossati G , et al. (2015) No -
4 Support Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose... Farwell Hagman KD , et al. (2016) No -
5 Positive Association Synaptosome-Associated Protein 25 (SNAP25) Gene Association Analysis Revealed Risk Variants for ASD, in Iranian Population. Safari MR , et al. (2016) Yes -
6 Support High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Hamdan FF , et al. (2017) No DD, ID
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.496G>T p.Asp166Tyr missense_variant De novo NA Simplex 29100083 Hamdan FF , et al. (2017)
c.142G>T p.Val48Phe missense_variant De novo NA - 27513193 Farwell Hagman KD , et al. (2016)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-64+26521C>T;c.-64+26285C>T;c.-64+18060C>T;c.-371+26521C>T - intron_variant - - - 21497654 Guerini FR , et al. (2011)
c.*239G>T - 3_prime_UTR_variant - - - 27888397 Safari MR , et al. (2016)
c.-63-21820G>A;c.-370-21820G>A A/G intron_variant - - - 25629685 Braida D , et al. (2015)
SFARI Gene score
3

Suggestive Evidence

SNAP25+/- mice exhibit hyperactivity, cognitive and social impairment (Braida et al., 2015). In this same report, a SNP encompassing a regulatory element of SNAP25 (rs363050) was shown to associate with both CARS scores (p=0.005) and cognitive scores (p=0.003) in an ASD cohort, while a SNP within intron 1 of the SNAP25 gene (rs363043) had previously been shown to associate with both increasing CARS (p=0.001) and hyperactivity scores (p=0.006) in a separate ASD cohort (Guerini et al., 2011). A SNP in the 3'UTR of the SNAP25 gene was shown to associate with ASD in an Iranian case-control association analysis (with an allele P-value of 2.0E-03) in Safari et al., 2017.

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

SNAP25+/- mice exhibit hyperactivity, cognitive and social impairment (Braida et al., 2015). In this same report, a SNP encompassing a regulatory element of SNAP25 (rs363050) was shown to associate with both CARS scores (p=0.005) and cognitive scores (p=0.003) in an ASD cohort, while a SNP within intron 1 of the SNAP25 gene (rs363043) had previously been shown to associate with both increasing CARS (p=0.001) and hyperactivity scores (p=0.006) in a separate ASD cohort (Guerini et al., 2011). A SNP in the 3'UTR of the SNAP25 gene was shown to associate with ASD in an Iranian case-control association analysis (with an allele P-value of 2.0E-03) in Safari et al., 2017.

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

Increased from to 4

Description

SNAP25+/- mice exhibit hyperactivity, cognitive and social impairment (Braida et al., 2015). In this same report, a SNP encompassing a regulatory element of SNAP25 (rs363050) was shown to associate with both CARS scores (p=0.005) and cognitive scores (p=0.003) in an ASD cohort, while a SNP within intron 1 of the SNAP25 gene (rs363043) had previously been shown to associate with both increasing CARS (p=0.001) and hyperactivity scores (p=0.006) in a separate ASD cohort (Guerini et al., 2011). A SNP in the 3'UTR of the SNAP25 gene was shown to associate with ASD in an Iranian case-control association analysis (with an allele P-value of 2.0E-03) in Safari et al., 2017.

Krishnan Probability Score

Score 0.76650813193569

Ranking 6/25841 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.
ExAC Score

Score 0.95980653025193

Ranking 2534/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.91495836343562

Ranking 8245/18665 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).
Zhang D Score

Score 0.25459764069435

Ranking 3412/20870 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.
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