PTPRA

Chr 20

protein tyrosine phosphatase receptor type A

Also known as: HEPTP, HLPR, HPTPA, HPTPalpha, LRP, PTPA, PTPRL2, R-PTP-alpha

NCBI Gene: 5786ENSG00000132670UniProt: P18433

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 contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. This PTP has been shown to dephosphorylate and activate Src family tyrosine kinases, and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

239
ClinVar variants
30
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PTPRA
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 165 VUS of 239 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.19LOEUF
pLI 1.000
Z-score 5.87
OE 0.08 (0.04–0.19)
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.
2.67Z-score
OE missense 0.65 (0.59–0.72)
307 obs / 469.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.08 (0.04–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.59–0.72)
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.0.93
0≤1.21.6
LoF obs/exp: 4 / 47.7Missense obs/exp: 307 / 469.8Syn Z: 0.74

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic6
VUS165
Likely Benign8
Benign6
Conflicting1
24
Pathogenic
6
Likely Pathogenic
165
VUS
8
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
23
0
24
Likely Pathogenic
3
0
3
0
6
VUS
4
140
20
1
165
Likely Benign
0
4
0
4
8
Benign
0
1
2
3
6
Conflicting
—1
Total8145488210

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

View in ClinVar →

Protein Context — Lollipop Plot

PTPRA · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases.
Wu Z et al.·Acta Neuropathol Commun
2024Cohort
Does a rare mutation in PTPRA contribute to the development of Parkinson's disease in an Australian multi-incident family?
Hill MA et al.·PLoS One
2022Case report
Increased PTPRA expression leads to poor prognosis through c-Src activation and G1 phase progression in squamous cell lung cancer.
Gu Z et al.·Int J Oncol
2017
Rare variants in Protein tyrosine phosphatase, receptor type A (PTPRA) in schizophrenia: Evidence from a family based study.
John J et al.·Schizophr Res
2019
Genome-wide association study reveals genetic variants associated with HIV-1C infection in a Botswana study population.
Shevchenko AK et al.·Proc Natl Acad Sci U S A
2021
Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.
Carotenuto M et al.·Sci Rep
2013
The CC2D2B is a novel genetic modifier of the clinical phenotype in patients with hereditary angioedema due to C1 inhibitor deficiency.
Rupar N et al.·Gene
2024Cohort
Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines.
Junnila S et al.·BMC Cancer
2010
Somatic mutations in specific and connected subpathways are associated with short neuroblastoma patients' survival and indicate proteins targetable at onset of disease.
Esposito MR et al.·Int J Cancer
2018Cohort
Genetic regulation of lipid metabolism in Han Chinese adolescents from Xinjiang: An extreme phenotype sequencing approach.
Yu J et al.·Medicine (Baltimore)
2025
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