Human Gene Module / Chromosome 1 / PTPRC

PTPRCprotein tyrosine phosphatase, receptor type, C

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 11
Rare Variants / Common Variants
6 / 1
Aliases
PTPRC, LCA,  LY5,  B220,  CD45,  T200,  CD45R,  GP180
Associated Syndromes
-
Chromosome Band
1q31.3-q32.1
Associated Disorders
-
Relevance to Autism

Rare deletions affecting the PTPRC gene have been identified with autism (Pinto et al., 2010). In addition, genetic association has been found between PTPRC and multiple sclerosis in the German population (Jacobsen et al., 2000).

Molecular Function

The encoded protein is a member of the protein tyrosine phosphatase (PTP) family that is an essential regulator of T- and B-cell antigen receptor signaling

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PTPRC (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A point mutation in PTPRC is associated with the development of multiple sclerosis Jacobsen M , et al. (2000) No -
2 Recent Recommendation Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL Oberdoerffer S , et al. (2008) No -
3 Recent Recommendation Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses Hermiston ML , et al. (2009) No -
4 Recent Recommendation Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk Raychaudhuri S , et al. (2009) No -
5 Recent Recommendation PTPRC mutation associated with response to anti-tNF therapy in rheumatoid arthritis Higgs R (2010) No -
6 Primary Functional impact of global rare copy number variation in autism spectrum disorders Pinto D , et al. (2010) Yes -
7 Highly Cited Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway Koretzky GA , et al. (1990) No -
8 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
9 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
10 Support - Woodbury-Smith M et al. (2022) Yes -
11 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 20531469 Pinto D , et al. (2010)
c.3893C>A p.Ala1298Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3319A>G p.Arg1107Gly missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1528G>A p.Asp510Asn missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1864_1864+3del - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.367G>C p.Asp123His missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.77C>G p.(=) splice_site_variant - - - 11101853 Jacobsen M , et al. (2000)
SFARI Gene score
2

Strong Candidate

Rare deletions affecting the PTPRC gene were identified in two ASD probands in Pinto et al., 2010. A missense variant in the PTPRC gene (Asp123His) that was located in a identical by descent (IBD) genomic region was present in all three affected family members in an ASD extended multiplex family in Cukier et al., 2014; while this missense variant was predicted to be damaging, it was also present in controls and dbSNP. In addition, genetic association has been found between PTPRC and multiple sclerosis in the German population (Jacobsen et al., 2000).

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

Rare deletions affecting the PTPRC gene were identified in two ASD probands in Pinto et al., 2010. A missense variant in the PTPRC gene (Asp123His) that was located in a identical by descent (IBD) genomic region was present in all three affected family members in an ASD extended multiplex family in Cukier et al., 2014; while this missense variant was predicted to be damaging, it was also present in controls and dbSNP. In addition, genetic association has been found between PTPRC and multiple sclerosis in the German population (Jacobsen et al., 2000).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare deletions affecting the PTPRC gene were identified in two ASD probands in Pinto et al., 2010. A missense variant in the PTPRC gene (Asp123His) that was located in a identical by descent (IBD) genomic region was present in all three affected family members in an ASD extended multiplex family in Cukier et al., 2014; while this missense variant was predicted to be damaging, it was also present in controls and dbSNP. In addition, genetic association has been found between PTPRC and multiple sclerosis in the German population (Jacobsen et al., 2000).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Rare deletions affecting the PTPRC gene were identified in two ASD probands in Pinto et al., 2010. A missense variant in the PTPRC gene (Asp123His) that was located in a identical by descent (IBD) genomic region was present in all three affected family members in an ASD extended multiplex family in Cukier et al., 2014; while this missense variant was predicted to be damaging, it was also present in controls and dbSNP. In addition, genetic association has been found between PTPRC and multiple sclerosis in the German population (Jacobsen et al., 2000).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2018
icon
4

Increased from to 4

Description

Rare deletions affecting the PTPRC gene were identified in two ASD probands in Pinto et al., 2010. A missense variant in the PTPRC gene (Asp123His) that was located in a identical by descent (IBD) genomic region was present in all three affected family members in an ASD extended multiplex family in Cukier et al., 2014; while this missense variant was predicted to be damaging, it was also present in controls and dbSNP. In addition, genetic association has been found between PTPRC and multiple sclerosis in the German population (Jacobsen et al., 2000).

Krishnan Probability Score

Score 0.44602110098153

Ranking 15053/25841 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 0.99994115614854

Ranking 605/18225 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 0.94318686901007

Ranking 15591/18665 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 3

Ranking 356/461 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 -0.11219673316465

Ranking 12816/20870 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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