PTPRG

Chr 3

protein tyrosine phosphatase receptor type G

Also known as: HPTPG, PTPG, R-PTP-GAMMA, RPTPG

NCBI Gene: 5793ENSG00000144724UniProt: P23470

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 intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this PTP contains a carbonic anhydrase-like (CAH) domain, which is also found in the extracellular region of PTPRBETA/ZETA. This gene is located in a chromosomal region that is frequently deleted in renal cell carcinoma and lung carcinoma, thus is thought to be a candidate tumor suppressor gene. [provided by RefSeq, Jul 2008]

273
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PTPRG
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 231 VUS of 273 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.45LOEUF
pLI 0.000
Z-score 5.44
OE 0.32 (0.23–0.45)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.23Z-score
OE missense 0.98 (0.92–1.03)
833 obs / 851.9 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.0.32 (0.23–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.92–1.03)
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.1.08
0≤1.21.6
LoF obs/exp: 24 / 74.8Missense obs/exp: 833 / 851.9Syn Z: -1.07

ClinVar Variant Classifications

273 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS231
Likely Benign27
Benign4
10
Pathogenic
1
Likely Pathogenic
231
VUS
27
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
223
8
0
231
Likely Benign
0
8
8
11
27
Benign
0
1
0
3
4
Total02322714273

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

View in ClinVar →

Protein Context — Lollipop Plot

PTPRG · 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
📖
GeneReview available — PTPRG
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association of common variants in TCF4 and PTPRG with Fuchs' corneal dystrophy: a systematic review and meta-analysis.
Lau LC et al.·PLoS One
2014Meta-analysis
Single-cell profiling uncovers PTPRG-driven stemness in malignant plasma cells and signatures of treatment failure in multiple myeloma.
Tan J et al.·Front Immunol
2025
Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.
Herold C et al.·Mol Psychiatry
2016Meta-analysis
Overexpression of long noncoding RNA PTPRG-AS1 is associated with poor prognosis in epithelial ovarian cancer.
Ren XY et al.·Rev Assoc Med Bras (1992)
2020
Characterization of PTPRG in knockdown and phosphatase-inactive mutant mice and substrate trapping analysis of PTPRG in mammalian cells.
Zhang W et al.·PLoS One
2012
miR-141 mediates recovery from acute kidney injury.
Newbury LJ et al.·Sci Rep
2021
Clinicopathological, Genomic, and Transcriptomic Feature Analysis of Primary Adrenal Large B-cell Lymphoma: Insights Into Immune-privileged Sites.
Deng S et al.·Am J Surg Pathol
2025
Gene Expression Landscape of Chronic Myeloid Leukemia K562 Cells Overexpressing the Tumor Suppressor Gene PTPRG.
Lombardi G et al.·Int J Mol Sci
2022
Exploring lncRNA expression in follicular fluid exosomes of patients with obesity and polycystic ovary syndrome based on high-throughput sequencing technology.
Xin X et al.·J Ovarian Res
2024Cohort
Long noncoding RNA PTPRG-AS1 acts as a microRNA-194-3p sponge to regulate radiosensitivity and metastasis of nasopharyngeal carcinoma cells via PRC1.
Yi L et al.·J Cell Physiol
2019
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools