PTPRN2

Chr 7

protein tyrosine phosphatase receptor type N2

Also known as: IA-2beta, IAR, ICAAR, PTPRP, R-PTP-N2

NCBI Gene: 5799ENSG00000155093UniProt: Q92932

This gene encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases. However, tyrosine phosphatase activity has not been experimentally validated for this protein. Studies of the rat ortholog suggest that the encoded protein may instead function as a phosphatidylinositol phosphatase with the ability to dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 4,5-diphosphate, and this function may be involved in the regulation of insulin secretion. This protein has been identified as an autoantigen in insulin-dependent diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

383
ClinVar variants
90
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PTPRN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
90 Pathogenic / Likely Pathogenic· 213 VUS of 383 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.
0.57LOEUF
pLI 0.000
Z-score 4.04
OE 0.39 (0.27–0.57)
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.
0.06Z-score
OE missense 0.99 (0.93–1.06)
630 obs / 634.1 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.0.39 (0.27–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.93–1.06)
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.0.98
0≤1.21.6
LoF obs/exp: 20 / 51.1Missense obs/exp: 630 / 634.1Syn Z: 0.24

ClinVar Variant Classifications

383 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic7
VUS213
Likely Benign48
Benign29
Conflicting3
83
Pathogenic
7
Likely Pathogenic
213
VUS
48
Likely Benign
29
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
7
0
7
VUS
0
182
31
0
213
Likely Benign
0
17
13
18
48
Benign
1
9
3
16
29
Conflicting
—3
Total120813734383

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

View in ClinVar →

Protein Context — Lollipop Plot

PTPRN2 · 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
Bioinformatic analysis constructs an optimal prognostic index for survival-related variables (OPISV) based on whole-genome expression data in Glioblastoma.
Pan J et al.·Int J Biol Macromol
2024
Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2.
Paniagua-Herranz L et al.·Int J Mol Sci
2024
Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis.
Tang X et al.·Brain
2025
Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study.
Torres-Martos Á et al.·Artif Intell Med
2024Natural history
Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population.
Gurung RL et al.·Diabetes Res Clin Pract
2024
Genome-wide methylation patterns in Marfan syndrome.
van Andel MM et al.·Clin Epigenetics
2021
Genetic variants associated with syncope implicate neural and autonomic processes.
Aegisdottir HM et al.·Eur Heart J
2023Meta-analysis
The association of genetically controlled CpG methylation (cg158269415) of protein tyrosine phosphatase, receptor type N2 (PTPRN2) with childhood obesity.
Lee S·Sci Rep
2019
Screening of genes interacting with high myopia and neuropsychiatric disorders.
Liu Y et al.·Sci Rep
2023
Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics.
van der Ende EL et al.·Ann Clin Transl Neurol
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