Human Gene Module / Chromosome 17 / PPP1R1B

PPP1R1BProtein phosphatase 1, regulatory (inhibitor) subunit 1B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
1 / 3
Aliases
PPP1R1B, DARPP-32,  DARPP32,  FLJ20940
Associated Syndromes
-
Chromosome Band
17q12
Associated Disorders
-
Relevance to Autism

Case-control and family-based association analysis of the PPP1R1B gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 443 controls revealed an increased frequency of the rs1495099 CC (p=0.002), rs907094 (p=0.028), and rs3764352 GG (p=0.025) genotypes in affected males compared to the comparison group (Hettinger et al., 2012). Family-based association tests in the same report showed significant over-transmission of the rs1495099 C allele (p=0.00092) to affected males under a recessive model.

Molecular Function

Inhibitor of protein-phosphatase 1. This gene encodes a bifunctional signal transduction molecule. Dopaminergic and glutamatergic receptor stimulation regulates its phosphorylation and function as a kinase or phosphatase inhibitor.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PPP1R1B (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary DRD2 and PPP1R1B (DARPP-32) polymorphisms independently confer increased risk for autism spectrum disorders and additively predict affected status in male-only affected sib-pair families Hettinger JA , et al. (2012) Yes -
2 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.457+2dup - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-439C>G;c.81+738C>G;c.-523C>G G>C intron_variant, 2KB_upstream_variant - - - 22559203 Hettinger JA , et al. (2012)
c.337+32G>A;c.445+32G>A T/C intron_variant - - - 22559203 Hettinger JA , et al. (2012)
c.337+600C>T;c.445+600C>T A>G intron_variant - - - 22559203 Hettinger JA , et al. (2012)
SFARI Gene score
2

Strong Candidate

Case-control and family-based association analysis of the PPP1R1B gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 443 controls revealed an increased frequency of the rs1495099 CC (p=0.002), rs907094 (p=0.028), and rs3764352 GG (p=0.025) genotypes in affected males compared to the comparison group (PMID 22559203). Family-based association tests in the same report showed significant over-transmission of the rs1495099 C allele (p=0.00092) to affected males under a recessive model.

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

Case-control and family-based association analysis of the PPP1R1B gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 443 controls revealed an increased frequency of the rs1495099 CC (p=0.002), rs907094 (p=0.028), and rs3764352 GG (p=0.025) genotypes in affected males compared to the comparison group (PMID 22559203). Family-based association tests in the same report showed significant over-transmission of the rs1495099 C allele (p=0.00092) to affected males under a recessive model.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Case-control and family-based association analysis of the PPP1R1B gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 443 controls revealed an increased frequency of the rs1495099 CC (p=0.002), rs907094 (p=0.028), and rs3764352 GG (p=0.025) genotypes in affected males compared to the comparison group (PMID 22559203). Family-based association tests in the same report showed significant over-transmission of the rs1495099 C allele (p=0.00092) to affected males under a recessive model.

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

Increased from No data to 4

Description

Case-control and family-based association analysis of the PPP1R1B gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 443 controls revealed an increased frequency of the rs1495099 CC (p=0.002), rs907094 (p=0.028), and rs3764352 GG (p=0.025) genotypes in affected males compared to the comparison group (PMID 22559203). Family-based association tests in the same report showed significant over-transmission of the rs1495099 C allele (p=0.00092) to affected males under a recessive model.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Case-control and family-based association analysis of the PPP1R1B gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 443 controls revealed an increased frequency of the rs1495099 CC (p=0.002), rs907094 (p=0.028), and rs3764352 GG (p=0.025) genotypes in affected males compared to the comparison group (PMID 22559203). Family-based association tests in the same report showed significant over-transmission of the rs1495099 C allele (p=0.00092) to affected males under a recessive model.

Krishnan Probability Score

Score 0.49539291116029

Ranking 2999/25841 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 0.082106282395609

Ranking 8064/18225 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 0.90195182562803

Ranking 6579/18665 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
Larsen Cumulative Evidence Score

Score 4

Ranking 321/461 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.
Original Source
Zhang D Score

Score 0.24619306592566

Ranking 3526/20870 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
CNVs associated with PPP1R1B(1 CNVs)
Sort By:
17q12 77 Deletion-Duplication 117  /  510
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
KLHL6 kelch-like family member 6 Human Protein Binding 89857 Q8WZ60
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