PTPRS
protein-codingprotein tyrosine phosphatase receptor type S, the group of Fibronectin type III domain containing|I-set domain containing|Protein tyrosine phosphatases receptor type
Gene summary
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. This PTP has been also implicated in the molecular control of adult nerve repair. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~182.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTPRS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002850.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 62 | 18 | 90 | ||
| missense | 1 | 328 | 9 | 3 | 341 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 1 | 345 | 71 | 21 | 438 |
Highest pathogenic variant AF is 0.000013023353
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002841.3 | 37 | MANE Select | |
| Ensembl | ENSP00000262963.8 | 37 | MANE Select | |
| RefSeq | NP_001380940.1 | 33 | Standard | |
| RefSeq | NP_001380941.1 | 33 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Extracellular matrix organization
- Neuronal System
- Synaptic adhesion-like molecules
- Receptor-type tyrosine-protein phosphatases
- ECM proteoglycans
Biological Process
- protein dephosphorylation
- negative regulation of neuron projection development
- spinal cord development
- cerebellum development
- hippocampus development
Molecular Function
- phosphoprotein phosphatase activity
- protein tyrosine phosphatase activity
- protein binding
- heparin binding
- chondroitin sulfate binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell junction
- integral component of synaptic vesicle membrane
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000357368
- Coding exons
- 37
- Length
- 182309
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 66
- Defined
- 125747
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.78 | 911 | 1.29e+3 | 0.704 | 0.0000943 | 12534 |
| Missense (PolyPhen) | 361 | 591.56 | 0.61026 | 5261 | ||
| Synonymous | -4.58 | 707 | 568 | 1.24 | 0.0000468 | 3986 |
| Loss of Function | 7.38 | 15 | 90.9 | 0.165 | 0.00000473 | 1012 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00016 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.0021 | 0.0020 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00073 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycan (PubMed:21454754). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth. Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection. Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as tyrosine phosphatase (PubMed:8524829). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (By similarity). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases (By similarity). Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (PubMed:26231120). {ECO:0000250|UniProtKB:B0V2N1, ECO:0000250|UniProtKB:F1NWE3, ECO:0000269|PubMed:21454754, ECO:0000269|PubMed:26231120, ECO:0000269|PubMed:8524829}.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.317
- RVIS EVS
- -4.37
- RVIS percentile EVS
- 0.1
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.726
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |