PTPRK
protein-codingprotein tyrosine phosphatase receptor type K, the group of Fibronectin type III domain containing|Immunoglobulin like 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 possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP was shown to mediate homophilic intercellular interaction, possibly through the interaction with beta- and gamma-catenin at adherens junctions. Expression of this gene was found to be stimulated by TGF-beta 1, which may be important for the inhibition of keratinocyte proliferation. [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 ~551.8 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 PTPRK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002844.4. 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 | 7 | 3 | 10 | |||
| missense | 160 | 1 | 161 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 174 | 1 | 3 | 178 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002835.2 | 30 | MANE Select | |
| Ensembl | ENSP00000357209.4 | 30 | MANE Select | |
| RefSeq | NP_001129120.1 | 31 | Standard | |
| RefSeq | NP_001278910.1 | 33 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- EGFR downregulation
- Signaling by EGFR
- EGFR1
- Signaling by Receptor Tyrosine Kinases
Biological Process
- protein dephosphorylation
- cell adhesion
- signal transduction
- transforming growth factor beta receptor signaling pathway
- negative regulation of cell population proliferation
Molecular Function
- protein tyrosine phosphatase activity
- transmembrane receptor protein tyrosine phosphatase activity
- protein binding
- beta-catenin binding
- protein kinase binding
Cellular Component
- photoreceptor outer segment
- plasma membrane
- integral component of plasma membrane
- cell-cell junction
- adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368213
- Coding exons
- 31
- Length
- 551947
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 53
- Defined
- 125748
- p
- 0.000215
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.17 | 551 | 804 | 0.685 | 0.0000428 | 9473 |
| Missense (PolyPhen) | 219 | 404.06 | 0.542 | 4897 | ||
| Synonymous | -0.272 | 294 | 288 | 1.02 | 0.0000160 | 2755 |
| Loss of Function | 6.68 | 17 | 82.5 | 0.206 | 0.00000472 | 920 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.00015 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis. Negative regulator of EGFR signaling pathway. Forms complexes with beta-catenin and gamma-catenin/plakoglobin. Beta-catenin may be a substrate for the catalytic activity of PTPRK/PTP-kappa. {ECO:0000269|PubMed:19836242}.;
Intolerance Scores
- LoFtool
- 0.665
- RVIS EVS
- -1.72
- RVIS percentile EVS
- 2.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.654
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |