Human Gene Module / Chromosome 15 / ARHGAP11B

ARHGAP11BRho GTPase activating protein 11B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 3
Rare Variants / Common Variants
2 / 0
Aliases
ARHGAP11B, B'-T,  FAM7B1,  GAP (1-8)
Associated Syndromes
-
Chromosome Band
15q13.2
Associated Disorders
ID
Relevance to Autism

Rare ARHGAP11B deletions were found in two patients with autism and intellectual disability (Leblond et al., 2012).

Molecular Function

This protein activates Rho-like small GTPases. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ARHGAP11B (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders Leblond CS , et al. (2012) Yes ID
2 Support De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes Vadgama N , et al. (2019) No -
3 Support Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis Namba T , et al. (2019) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Maternal Simplex 22346768 Leblond CS , et al. (2012)
- - copy_number_loss De novo - Multiplex (monozygotic twins) 30886340 Vadgama N , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Maternally-inherited exonic deletions affecting the ARHGAP11B gene were identified in two unrelated ASD probands from simplex families in Leblond et al., 2012; however, subsequent studies failed to show statistically significant enrichment of ARHGAP11B deletions in ASD cases compared to controls [8 of 1257 patients with ASD (0.64%) vs. 4 of 1577 controls (0.25%), Fisher's exact test, 2-sided P=0.15].

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Maternally-inherited exonic deletions affecting the ARHGAP11B gene were identified in two unrelated ASD probands from simplex families in Leblond et al., 2012; however, subsequent studies failed to show statistically significant enrichment of ARHGAP11B deletions in ASD cases compared to controls [8 of 1257 patients with ASD (0.64%) vs. 4 of 1577 controls (0.25%), Fisher's exact test, 2-sided P=0.15].

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

Maternally-inherited exonic deletions affecting the ARHGAP11B gene were identified in two unrelated ASD probands from simplex families in Leblond et al., 2012; however, subsequent studies failed to show statistically significant enrichment of ARHGAP11B deletions in ASD cases compared to controls [8 of 1257 patients with ASD (0.64%) vs. 4 of 1577 controls (0.25%), Fisher's exact test, 2-sided P=0.15].

Reports Added
[Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis.2019]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Maternally-inherited exonic deletions affecting the ARHGAP11B gene were identified in two unrelated ASD probands from simplex families in Leblond et al., 2012; however, subsequent studies failed to show statistically significant enrichment of ARHGAP11B deletions in ASD cases compared to controls [8 of 1257 patients with ASD (0.64%) vs. 4 of 1577 controls (0.25%), Fisher's exact test, 2-sided P=0.15].

Reports Added
[New Scoring Scheme]
4/1/2019
4
icon
4

Decreased from 4 to 4

Description

Maternally-inherited exonic deletions affecting the ARHGAP11B gene were identified in two unrelated ASD probands from simplex families in Leblond et al., 2012; however, subsequent studies failed to show statistically significant enrichment of ARHGAP11B deletions in ASD cases compared to controls [8 of 1257 patients with ASD (0.64%) vs. 4 of 1577 controls (0.25%), Fisher's exact test, 2-sided P=0.15].

Reports Added
[De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes.2019]
10/1/2018
icon
4

Increased from to 4

Description

Maternally-inherited exonic deletions affecting the ARHGAP11B gene were identified in two unrelated ASD probands from simplex families in Leblond et al., 2012; however, subsequent studies failed to show statistically significant enrichment of ARHGAP11B deletions in ASD cases compared to controls [8 of 1257 patients with ASD (0.64%) vs. 4 of 1577 controls (0.25%), Fisher's exact test, 2-sided P=0.15].

Krishnan Probability Score

Score 0.44492025399145

Ranking 15662/25841 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 0.072132342890547

Ranking 8175/18225 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 0.93152598014665

Ranking 11724/18665 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
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