PTPRZ1

Chr 7

protein tyrosine phosphatase receptor type Z1

Also known as: HPTPZ, HPTPzeta, PTP-ZETA, PTP18, PTPRZ, PTPZ, R-PTP-zeta-2, RPTPB

NCBI Gene: 5803ENSG00000106278UniProt: P23471

This gene encodes a member of the receptor protein tyrosine phosphatase family. Expression of this gene is restricted to the central nervous system (CNS), and it may be involved in the regulation of specific developmental processes in the CNS. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

326
ClinVar variants
22
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— PTPRZ1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 280 VUS of 326 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.29LOEUF
pLI 0.990
Z-score 7.22
OE 0.19 (0.13–0.29)
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.
0.85Z-score
OE missense 0.93 (0.89–0.98)
1103 obs / 1185.6 exp
Tolerant

Mild missense constraint

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.0.19 (0.13–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.89–0.98)
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.0.94
0≤1.21.6
LoF obs/exp: 18 / 93.2Missense obs/exp: 1103 / 1185.6Syn Z: 1.05

ClinVar Variant Classifications

326 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS280
Likely Benign17
Benign7
21
Pathogenic
1
Likely Pathogenic
280
VUS
17
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
274
5
1
280
Likely Benign
0
11
2
4
17
Benign
0
2
1
4
7
Total0287309326

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

View in ClinVar →

Protein Context — Lollipop Plot

PTPRZ1 · 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
Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor.
Hu H et al.·Cell
2018
PTPRZ1-Targeting RNA CAR T Cells Exert Antigen-Specific and Bystander Antitumor Activity in Glioblastoma.
Martinez Bedoya D et al.·Cancer Immunol Res
2024
Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen.
Chih YC et al.·Nat Commun
2025
The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization.
Wang Y et al.·Cell Signal
2024
A novel PTPRZ1-ETV1 fusion in gliomas.
Matjašič A et al.·Brain Pathol
2020
Evolving Molecular Genetics of Glioblastoma.
Li QJ et al.·Chin Med J (Engl)
2016Review
PTN-PTPRZ1 signaling axis blocking mediates tumor microenvironment remodeling for enhanced glioblastoma treatment.
Yang M et al.·J Control Release
2023Functional
Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma.
Nejo T et al.·Sci Rep
2024
Recurrent PTPRZ1-MET fusion and a high occurrence rate of MET exon 14 skipping in brain metastases.
Chai RC et al.·Cancer Sci
2022
Genetic basis of hyperlysinemia.
Houten SM et al.·Orphanet J Rare Dis
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Glioblastoma

A Study of PLB1001 Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).

ACTIVE NOT RECRUITING
NCT06105619Phase PHASE2, PHASE3Beijing Pearl Biotechnology Limited Liability CompanyStarted 2018-10-08
PLB1001TemozolomideCisplatin combined with Etoposide

External Resources

Links to major genomics databases and tools