Human Gene Module / Chromosome X / SYAP1

SYAP1Synapse associated protein 1

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
2 / 0
Aliases
SYAP1, PRO3113
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Xp22.2
Associated Disorders
-
Relevance to Autism

A novel recurrent duplication involving the SYAP1 gene was identified in two unrelated ASD cases (Prasad et al., 2012).

Molecular Function

SYAP1 is the human homolog of the SAP47 gene in Drosophila. Lack of SAP47 in Drosophila results in impaired short-term synaptic and behavioral plasticity (Saumweber et al., 2011).

Reports related to SYAP1 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Behavioral and synaptic plasticity are impaired upon lack of the synaptic protein SAP47. Saumweber T , et al. (2011) No -
2 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder. Prasad A , et al. (2013) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain Familial Maternal Simplex 23275889 Prasad A , et al. (2013)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A recurrent 19.17 kb exon-disrupting duplication affecting the SYAP1 gene was identified in two unrelated male ASD probands in Prasad et al., 2012; however, this duplication was also transmitted to an unaffected male sibling in one family, and there was no comparison with controls reported. SYAP1 is the human homolog of the SAP47 gene in Drosophila; lack of SAP47 in Drosophila results in impaired short-term synaptic and behavioral plasticity (Saumweber et al., 2011).

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

A recurrent 19.17 kb exon-disrupting duplication affecting the SYAP1 gene was identified in two unrelated male ASD probands in Prasad et al., 2012; however, this duplication was also transmitted to an unaffected male sibling in one family, and there was no comparison with controls reported. SYAP1 is the human homolog of the SAP47 gene in Drosophila; lack of SAP47 in Drosophila results in impaired short-term synaptic and behavioral plasticity (Saumweber et al., 2011).

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

Increased from to 4

Description

A recurrent 19.17 kb exon-disrupting duplication affecting the SYAP1 gene was identified in two unrelated male ASD probands in Prasad et al., 2012; however, this duplication was also transmitted to an unaffected male sibling in one family, and there was no comparison with controls reported. SYAP1 is the human homolog of the SAP47 gene in Drosophila; lack of SAP47 in Drosophila results in impaired short-term synaptic and behavioral plasticity (Saumweber et al., 2011).

Krishnan Probability Score

Score 0.4142370965352

Ranking 21685/25841 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 0.50211006775461

Ranking 5440/18225 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 0.92168554086735

Ranking 9424/18665 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 -0.15370989239113

Ranking 14232/20870 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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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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