Human Gene Module / Chromosome 20 / PTPRT

PTPRTprotein tyrosine phosphatase, receptor type, T

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 12
Rare Variants / Common Variants
14 / 0
Aliases
PTPRT, RP5-1121H13.2,  RPTPrho
Associated Syndromes
-
Chromosome Band
20q12-q13.11
Associated Disorders
-
Relevance to Autism

A rare duplication of the PTPRT gene was found in an individual with ASD (Christian et al., 2008).

Molecular Function

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. The protein domain structure and the expression pattern of the mouse counterpart of this PTP suggest its roles in both signal transduction and cellular adhesion in the central nervous system. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PTPRT (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder Christian SL , et al. (2008) Yes -
2 Support Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn Lim SH , et al. (2009) No -
3 Support Regulation of dendritic arborization by BCR Rac1 GTPase-activating protein, a substrate of PTPRT Park AR , et al. (2012) No -
4 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
5 Recent Recommendation Inactivation of the catalytic phosphatase domain of PTPRT/RPTP? increases social interaction in mice Thirtamara Rajamani K , et al. (2014) No -
6 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
7 Support Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease Karaca E , et al. (2015) No Microcephaly, hypotonia
8 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
9 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
10 Support - Zhou X et al. (2022) Yes -
11 Support - More RP et al. (2023) Yes -
12 Support - Marta Viggiano et al. (2024) Yes ID
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial - - 18374305 Christian SL , et al. (2008)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
c.42G>C p.Arg14Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.796C>T p.Arg266Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1156C>A p.Pro386Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2693C>T p.Thr898Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1561-3C>T - intron_variant Familial - Simplex 26539891 Karaca E , et al. (2015)
c.2916G>A p.Trp972Ter synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.796C>T p.Arg266Cys missense_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.548G>A p.Arg183Gln missense_variant De novo - Multiplex 30504930 Guo H , et al. (2018)
c.206T>C p.Val69Ala missense_variant Familial - Simplex 26539891 Karaca E , et al. (2015)
c.3386C>G p.Thr1129Arg missense_variant Familial - Multiplex 36702863 More RP et al. (2023)
c.1076G>A p.Arg359Gln missense_variant De novo - Simplex 38519481 Marta Viggiano et al. (2024)
c.2563G>A p.Gly855Arg missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A rare inherited duplication of the PTPRT gene was found in an individual with ASD (Christian et al., 2008). A likely damaging de novo missense variant in the PTPRT gene was identified in an ASD proband from a cohort of 200 Canadian ASD trio families in Yuen et al., 2016. Inactivation of the catalytic phosphatase domain of PTPRT increased social interaction in mice (Thirtamara Rajamani et al., 2015). Studies have demonstrated that PTPRT is involved in the regulation of synapse formation (Lim et al., 2009; Park et al., 2012).

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

A rare inherited duplication of the PTPRT gene was found in an individual with ASD (Christian et al., 2008). A likely damaging de novo missense variant in the PTPRT gene was identified in an ASD proband from a cohort of 200 Canadian ASD trio families in Yuen et al., 2016. Inactivation of the catalytic phosphatase domain of PTPRT increased social interaction in mice (Thirtamara Rajamani et al., 2015). Studies have demonstrated that PTPRT is involved in the regulation of synapse formation (Lim et al., 2009; Park et al., 2012).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A rare inherited duplication of the PTPRT gene was found in an individual with ASD (Christian et al., 2008). A likely damaging de novo missense variant in the PTPRT gene was identified in an ASD proband from a cohort of 200 Canadian ASD trio families in Yuen et al., 2016. Inactivation of the catalytic phosphatase domain of PTPRT increased social interaction in mice (Thirtamara Rajamani et al., 2015). Studies have demonstrated that PTPRT is involved in the regulation of synapse formation (Lim et al., 2009; Park et al., 2012).

Reports Added
[New Scoring Scheme]
10/1/2018
4
icon
4

Decreased from 4 to 4

Description

A rare inherited duplication of the PTPRT gene was found in an individual with ASD (Christian et al., 2008). A likely damaging de novo missense variant in the PTPRT gene was identified in an ASD proband from a cohort of 200 Canadian ASD trio families in Yuen et al., 2016. Inactivation of the catalytic phosphatase domain of PTPRT increased social interaction in mice (Thirtamara Rajamani et al., 2015). Studies have demonstrated that PTPRT is involved in the regulation of synapse formation (Lim et al., 2009; Park et al., 2012).

Reports Added
[Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]
7/1/2018
icon
4

Increased from to 4

Description

A rare inherited duplication of the PTPRT gene was found in an individual with ASD (Christian et al., 2008). A likely damaging de novo missense variant in the PTPRT gene was identified in an ASD proband from a cohort of 200 Canadian ASD trio families in Yuen et al., 2016. Inactivation of the catalytic phosphatase domain of PTPRT increased social interaction in mice (Thirtamara Rajamani et al., 2015). Studies have demonstrated that PTPRT is involved in the regulation of synapse formation (Lim et al., 2009; Park et al., 2012).

Krishnan Probability Score

Score 0.62577606535511

Ranking 75/25841 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 0.99999889319468

Ranking 307/18225 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 0.95053905180913

Ranking 18532/18665 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 0.33146426067409

Ranking 2273/20870 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
Submit New Gene

Report an Error