Human Gene Module / Chromosome 19 / PTPRS

PTPRSprotein tyrosine phosphatase receptor type S

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
8 / 10
Rare Variants / Common Variants
12 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19p13.3
Associated Disorders
-
Relevance to Autism

Chen et al., 2025 integrated cortex cell-specific cis-regulatory element annotations, a deep learning-based variant prediction model, and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 non-coding de novo mutations (ncDNMs) in ASD probands from Simons Simplex Collection (SSC) and Autism Speaks MSSNG resource (MSSNG) cohorts and identified a ncDNM that down-regulated expression of the PTPRS gene in a MSSNG proband. Additional de novo variants in the PTPRS gene, including a loss-of-function variant and four missense variants, have been identified in ASD probands (Iossifov et al., 2014; Krumm et al., 2015; Satterstrom et al., 2020; Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022).

Molecular Function

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of multiple Ig-like and fibronectin type III-like domains. Studies of the similar gene in mice suggested that this PTP may be involved in cell-cell interaction, primary axonogenesis, and axon guidance during embryogenesis and has also been implicated in the molecular control of adult nerve repair (Thompson et al., 2003 found that mice lacking RPTPsigma exhibited an accelerated rate of functional recovery following facial nerve crush, and Kirkham et al., 2006 found that neural stem cells from protein tyrosine

External Links
Gene CardPubMed
Human
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SFARI Genomic Platforms
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Reports related to PTPRS (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - K M Thompson et al. (2003) No -
2 Support - David L Kirkham et al. (2006) No -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
5 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Fu JM et al. (2022) Yes -
8 Support - Trost B et al. (2022) Yes -
9 Primary - Congcong Chen et al. () Yes -
10 Support - Richard G Boles et al. (2025) Yes DD, ID, epilepsy/seizures
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G>T - intergenic_variant De novo - Multiplex 40738258 Congcong Chen et al. ()
c.3597G>A p.Ser1199= synonymous_variant De novo - - 35982160 Fu JM et al. (2022)
c.4770-1G>C p.? splice_site_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1403C>T p.Pro468Leu missense_variant De novo - Unknown 35982159 Zhou X et al. (2022)
c.510G>A p.Lys170= synonymous_variant De novo - Simplex 36368308 Trost B et al. (2022)
c.4318+7C>T p.? splice_region_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.613A>G p.Ser205Gly missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2517G>A p.Ser839= synonymous_variant De novo - Unknown 36368308 Trost B et al. (2022)
c.1227C>T p.Gly422= synonymous_variant De novo - - 41010044 Richard G Boles et al. (2025)
c.2425G>T p.Val809Leu missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.4400C>T p.Pro1467Leu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3930C>T p.Pro1310= synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2025
3

Initial score established: 3

Krishnan Probability Score

Score 0.49463560341705

Ranking 3537/25841 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 0.76091506045435

Ranking 4150/18225 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 0.95008592376171

Ranking 18352/18665 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 0.15989780960243

Ranking 4980/20870 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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