PTPRK

Chr 6

protein tyrosine phosphatase receptor type K

NCBI Gene: 5796ENSG00000152894UniProt: Q15262

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

177
ClinVar variants
16
Pathogenic / LP
0.90
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PTPRK
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 155 VUS of 177 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.31LOEUF
pLI 0.903
Z-score 6.68
OE 0.21 (0.14–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.17Z-score
OE missense 0.69 (0.64–0.73)
551 obs / 803.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.14–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.64–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 17 / 82.5Missense obs/exp: 551 / 803.9Syn Z: -0.27

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS155
Likely Benign3
Benign3
13
Pathogenic
3
Likely Pathogenic
155
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
3
0
3
VUS
0
146
9
0
155
Likely Benign
0
1
2
0
3
Benign
0
0
0
3
3
Total0147273177

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PTPRK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Protein tyrosine phosphatase kappa (PTPRK) is a negative regulator of adhesion and invasion of breast cancer cells, and associates with poor prognosis of breast cancer.
Sun PH et al.·J Cancer Res Clin Oncol
2013
Molecular pathogenic pathways in extranodal NK/T cell lymphoma.
de Mel S et al.·J Hematol Oncol
2019Review
Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer.
Jeong JH et al.·PLoS One
2022
Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer.
Hashimoto T et al.·Br J Cancer
2022
MiR-1260b promotes the migration and invasion in non-small cell lung cancer via targeting PTPRK.
Xu L et al.·Pathol Res Pract
2018
RSPO fusion transcripts in colorectal cancer in Japanese population.
Shinmura K et al.·Mol Biol Rep
2014
Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling.
Kim M et al.·Int J Mol Sci
2018Review
Genomic and transcriptomic analysis of Korean colorectal cancer patients.
Jeon SA et al.·Genes Genomics
2022Cohort
The mutational landscape and prognostic indicators of pseudomyxoma peritonei originating from the ovary.
Wang B et al.·Int J Cancer
2021
Thymocyte regulatory variant alters transcription factor binding and protects from type 1 diabetes in infants.
Sandholm N et al.·Sci Rep
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PTPRK promotes resiniferatoxin-induced postherpetic neuralgia via activating DUSP1/p38 MAPK signaling pathway in dorsal root ganglia.
Zhao Y et al.·Sci Rep
2025🔓 Open Access
Protein tyrosine phosphatase receptor type kappa (PTPRK) revisited: evolving insights into structure, function, and pathology.
Zheng C et al.·J Transl Med
2025🔓 Open Access
PTPRK regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity.
Gilglioni EH et al.·Nat Commun
2024🔓 Open Access
The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.
Young KA et al.·J Cell Sci
2024🔓 Open Access
PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal Organoids.
Nanayakkara M et al.·Cells
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools