PTPRO

Chr 12AR

protein tyrosine phosphatase receptor type O

Also known as: GLEPP1, NPHS6, PTP-OC, PTP-U2, PTPROT, PTPU2, R-PTP-O

NCBI Gene: 5800ENSG00000151490UniProt: Q92729

This gene encodes a receptor-type protein tyrosine phosphatase that dephosphorylates CTNNB1 and regulates cell adhesion, proliferation, and epithelial integrity. Biallelic mutations cause autosomal recessive nephrotic syndrome type 6, affecting kidney function. The gene is highly constrained against loss-of-function variants (LOEUF 0.474), suggesting intolerance to protein disruption.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Nephrotic syndrome, type 6MIM #614196
AR
0
Active trials
10
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.47
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PTPRO
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 192 VUS of 399 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.000
Z-score 4.97
OE 0.33 (0.23–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.30Z-score
OE missense 0.86 (0.80–0.92)
561 obs / 654.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.23–0.47)
0≤0.351.4
Missense OE0.86 (0.80–0.92)
0≤0.61.4
Synonymous OE1.14
0≤1.21.6
LoF obs/exp: 21 / 63.8Missense obs/exp: 561 / 654.9Syn Z: -1.69
DN
0.6938th %ile
GOF
0.6833th %ile
LOF
0.2874th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median
LOF38% of P/LP variants are LoF · LOEUF 0.47

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

399 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic4
VUS192
Likely Benign124
Benign40
Conflicting6
12
Pathogenic
4
Likely Pathogenic
192
VUS
124
Likely Benign
40
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
10
0
12
Likely Pathogenic
4
0
0
0
4
VUS
0
171
11
10
192
Likely Benign
0
7
66
51
124
Benign
0
1
33
6
40
Conflicting
—6
Total617912067378

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

View in ClinVar →

Protein Context — Lollipop Plot

PTPRO · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients