PTPN3
Chr 9protein tyrosine phosphatase non-receptor type 3
Also known as: PTP-H1, PTPH1
The protein encoded by PTPN3 is a tyrosine phosphatase that dephosphorylates substrate proteins and acts at membrane-cytoskeleton junctions, regulating cellular processes including cell growth, differentiation, and cell cycle progression. Mutations cause disease through a dominant-negative mechanism, as indicated by the gene's extremely low tolerance to loss-of-function variants. However, the specific pediatric neurological phenotypes associated with PTPN3 mutations are not established in the provided data.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-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.
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.
ClinVar Variant Classifications
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 19 | 0 | 19 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 138 | 1 | 0 | 139 |
Likely Benign | 0 | 3 | 0 | 3 | 6 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 141 | 25 | 4 | 170 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PTPN3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools