Human Gene Module / Chromosome 12 / PTPRB

PTPRBprotein tyrosine phosphatase, receptor type B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
5 / 1
Aliases
PTPRB, PTPB,  HPTPB,  VEPTP,  HPTP-BETA,  R-PTP-BETA
Associated Syndromes
-
Chromosome Band
12q15
Associated Disorders
-
Relevance to Autism

The same diplotype comprising three SNPs (rs6102794, rs6072694 and rs6102795) was implicated in both independent populations (stages) (Wittkowski et al., 2014).

Molecular Function

A member of the protein tyrosine phosphatase (PTP) family. This PTP belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. The functions of the interaction partners of this protein implicate roles in cell adhesion, neurite growth, and neuronal differentiation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PTPRB (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A novel computational biostatistics approach implies impaired dephosphorylation of growth factor receptors as associated with severity of autism Wittkowski KM , et al. (2014) Yes -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
4 Support - Woodbury-Smith M et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Wang J et al. (2023) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.229G>A p.Gly77Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5354G>A p.Cys1785Tyr missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.3846G>T p.Gln1282His missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.1299C>A p.Ala433%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1701C>T p.Val567%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.5387+1843G>A;c.4463+1843G>A;c.5123+1843G>A;c.4733+1843G>A;c.3035+1843G>A - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
2

Strong Candidate

Analysis from two independent populations using u-statistics for genetically structured wide-locus data and added data from unrelated controls to explore epistasis identified PTPRB as a gene involved in ASD (Wittkowski et al., 2014), with the region of high significance in PTPRB comprised of the same SNPs in both independent stages. An intronic SNP in the PTPRB gene demonstrated significant association with ASD (6.16E-05) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium 2017). A novel de novo missense variant that was predicted to be damaging was identified in the PTPRB gene in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

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

Analysis from two independent populations using u-statistics for genetically structured wide-locus data and added data from unrelated controls to explore epistasis identified PTPRB as a gene involved in ASD (Wittkowski et al., 2014), with the region of high significance in PTPRB comprised of the same SNPs in both independent stages. An intronic SNP in the PTPRB gene demonstrated significant association with ASD (6.16E-05) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium 2017). A novel de novo missense variant that was predicted to be damaging was identified in the PTPRB gene in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Analysis from two independent populations using u-statistics for genetically structured wide-locus data and added data from unrelated controls to explore epistasis identified PTPRB as a gene involved in ASD (Wittkowski et al., 2014), with the region of high significance in PTPRB comprised of the same SNPs in both independent stages. An intronic SNP in the PTPRB gene demonstrated significant association with ASD (6.16E-05) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium 2017). A novel de novo missense variant that was predicted to be damaging was identified in the PTPRB gene in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

Analysis from two independent populations using u-statistics for genetically structured wide-locus data and added data from unrelated controls to explore epistasis identified PTPRB as a gene involved in ASD (Wittkowski et al., 2014), with the region of high significance in PTPRB comprised of the same SNPs in both independent stages. An intronic SNP in the PTPRB gene demonstrated significant association with ASD (6.16E-05) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium 2017). A novel de novo missense variant that was predicted to be damaging was identified in the PTPRB gene in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

Krishnan Probability Score

Score 0.49796889231407

Ranking 2311/25841 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 0.94350294120823

Ranking 2791/18225 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 0.8519622455321

Ranking 3533/18665 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 0.17719651674773

Ranking 4663/20870 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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