Human Gene Module / Chromosome 7 / PIK3CG

PIK3CGphosphoinositide-3-kinase, catalytic, gamma polypeptide

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 5
Rare Variants / Common Variants
1 / 1
Aliases
PIK3CG, PI3K,  PIK3,  PI3CG,  PI3Kgamma
Associated Syndromes
-
Chromosome Band
7q22.3
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the PIK3CG gene and autism in an AGRE cohort (Serajee et al., 2003).

Molecular Function

The encoded protein has phosphatidylinositol 3-kinase activity.

SFARI Genomic Platforms
Reports related to PIK3CG (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation Hirsch E , et al. (2000) No -
2 Primary Association of INPP1, PIK3CG, and TSC2 gene variants with autistic disorder: implications for phosphatidylinositol signalling in autism Serajee FJ , et al. (2003) Yes Tuberous Sclerosis
3 Recent Recommendation Rac1 modulates sphingosine 1-phosphate-mediated activation of phosphoinositide 3-kinase/Akt signaling pathways in vascular endothelial cells Gonzalez E , et al. (2005) No -
4 Recent Recommendation Continuous signaling via PI3K isoforms beta and gamma is required for platelet ADP receptor function in dynamic thrombus stabilization Cosemans JM , et al. (2006) No -
5 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.636G>A p.Trp212Ter stop_gained 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
c.2025C>T p.(=) synonymous_variant - - - 14627686 Serajee FJ , et al. (2003)
SFARI Gene score
2

Strong Candidate

Association report but not genome-wide significant nor replicated (Serajee et al., 2003).

Score Delta: Score remained at 2

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
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2

Decreased from 3 to 2

Description

Association report but not genome-wide significant nor replicated (Serajee et al., 2003).

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

Association report but not genome-wide significant nor replicated (Serajee et al., 2003).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Association report but not genome-wide significant nor replicated (Serajee et al., 2003).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Association report but not genome-wide significant nor replicated (Serajee et al., 2003).

Krishnan Probability Score

Score 0.47324306769808

Ranking 8744/25841 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 0.56396387141262

Ranking 5160/18225 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 0.94669023402754

Ranking 16972/18665 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).
Larsen Cumulative Evidence Score

Score 1

Ranking 428/461 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.
Zhang D Score

Score 0.024519046798894

Ranking 7946/20870 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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