Human Gene Module / Chromosome 17 / PPP1R9B

PPP1R9Bprotein phosphatase 1 regulatory subunit 9B

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
8 / 0
EAGLE Score
1.5
Limited Learn More
Aliases
PPP1R9B, PPP1R6,  PPP1R9,  SPINO,  Spn
Associated Syndromes
-
Chromosome Band
17q21.33
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

Three de novo missense variants, including two that were predicted to be damaging (defined as MPC 2), were identified in the PPP1R9B gene in ASD probands from the Autism Sequencing Consortium (Satterstrom et al., 2020). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified PPP1R9B as a candidate gene with a false discovery rate (FDR) between 0.05 and 0.1 (0.05 < FDR 0.1).

Molecular Function

This gene encodes a scaffold protein that functions as a regulatory subunit of protein phosphatase 1a. Expression of this gene is particularly high in dendritic spines, suggesting that the encoded protein may play a role in receiving signals from the central nervous system.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to PPP1R9B (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Mahjani B et al. (2021) Yes -
3 Support - Woodbury-Smith M et al. (2022) Yes -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.827C>T p.Pro276Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.984G>A p.Glu328%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1891G>A p.Glu631Lys missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.2252G>A p.Arg751His missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1929C>T p.Ile643%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1798G>A p.Glu600Lys missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2105T>G p.Val702Gly missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2252G>A p.Arg751His missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.49639065997371

Ranking 2609/25841 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 0.9972869137405

Ranking 1333/18225 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 0.93676046329323

Ranking 13301/18665 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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