Human Gene Module / Chromosome 1 / SMAP2

SMAP2small ArfGAP2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
3 / 1
Aliases
-
Associated Syndromes
-
Chromosome Band
1p34.2
Associated Disorders
-
Relevance to Autism

A window-based analysis of common and low-frequency genetic variation from 2,836 ASD trios from the MSSNG cohort with the summary statistics of the population-based meta-analysis from the iPSYCH project using KnockoffHybrid-Z, a statistical method for the analysis of trio and population data in genome-wide association studies, in Yang et al., 2024, identified SMAP2 as a significant loci with a false discovery rate (FDR) at 0.1 (ATAC p-value 2.05E-06). SMAP2 was initially proposed as an ASD candidate gene based on GWAS of genetic data from the Autism Genome Project in Wittkowski et al., 2014. A de novo loss-of-function variant in the SMAP2 gene has been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while an inherited loss-of-function variant in this gene was observed in one of two ASD-affected siblings in an AGRE multiplex family (Cirnigliaro et al., 2023). Exome sequencing of 231 parent-proband trios enriched for sporadic schizophrenia cases and 34 unaffected trios identified a de novo missense variant in the SMAP2 gene in an adult schizophrenia proband (Xu et al., 2012).

Molecular Function

Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SMAP2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Bin Xu et al. (2012) No -
2 Positive Association A novel computational biostatistics approach implies impaired dephosphorylation of growth factor receptors as associated with severity of autism Wittkowski KM , et al. (2014) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
5 Primary - Yi Yang et al. () Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.354T>A p.Tyr118Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.896G>A p.Ser299Asn missense_variant De novo - Simplex 23042115 Bin Xu et al. (2012)
c.233+1G>A - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - intron_variant - - - 38821058 Yi Yang et al. ()
SFARI Gene score
2

Strong Candidate

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.

7/1/2024
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2

Increased from to 2

Krishnan Probability Score

Score 0.45237384796067

Ranking 10497/25841 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
ExAC Score

Score 0.014285645188747

Ranking 9724/18225 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
Original Source
Sanders TADA Score

Score 0.47786777524834

Ranking 403/18665 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
Zhang D Score

Score 0.28006974959804

Ranking 3030/20870 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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