Human Gene Module / Chromosome 2 / ASAP2

ASAP2ArfGAP with SH3 domain, ankyrin repeat and PH domain 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
6 / 0
Aliases
ASAP2, AMAP2,  CENTB3,  DDEF2,  PAG3,  PAP,  Pap-alpha,  SHAG1
Associated Syndromes
-
Chromosome Band
2p25.1
Associated Disorders
-
Relevance to Autism

Rare de novo missense variants in the ASAP2 gene were identified in ASD probands by whole-exome sequencing in De Rubeis et al., 2014 and by whole-genome sequencing in Yuen et al., 2016. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the ASAP2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [1 CNV from ASD cases and 4 CNVs from SCZ cases (5 total) vs. 0 CNVs in controls (Odds ratio 7.68, P = 1.0E-05)].

Molecular Function

The encoded protein has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ASAP2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
3 Recent Recommendation Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights Kushima I , et al. (2018) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - - 30208311 Kushima I , et al. (2018)
c.1576A>G p.Ile526Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.602A>G p.Tyr201Cys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.517A>T p.Met173Leu missense_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.1718C>T p.Thr573Met missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2027C>T p.Ala676Val missense_variant De novo - Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Rare de novo missense variants in the ASAP2 gene were identified in ASD probands by whole-exome sequencing in De Rubeis et al., 2014 and by whole-genome sequencing in Yuen et al., 2016. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the ASAP2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [1 CNV from ASD cases and 4 CNVs from SCZ cases (5 total) vs. 0 CNVs in controls (Odds ratio 7.68, P = 1.0E-05)].

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Rare de novo missense variants in the ASAP2 gene were identified in ASD probands by whole-exome sequencing in De Rubeis et al., 2014 and by whole-genome sequencing in Yuen et al., 2016. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the ASAP2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [1 CNV from ASD cases and 4 CNVs from SCZ cases (5 total) vs. 0 CNVs in controls (Odds ratio 7.68, P = 1.0E-05)].

Reports Added
[New Scoring Scheme]
10/1/2018
icon
3

Increased from to 3

Description

Rare de novo missense variants in the ASAP2 gene were identified in ASD probands by whole-exome sequencing in De Rubeis et al., 2014 and by whole-genome sequencing in Yuen et al., 2016. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the ASAP2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [1 CNV from ASD cases and 4 CNVs from SCZ cases (5 total) vs. 0 CNVs in controls (Odds ratio 7.68, P = 1.0E-05)].

Krishnan Probability Score

Score 0.49661447704177

Ranking 2554/25841 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 0.99998604336681

Ranking 484/18225 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 0.90330357110518

Ranking 6723/18665 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 0.11720873581889

Ranking 5779/20870 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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