PTPN1
Chr 20ADprotein tyrosine phosphatase non-receptor type 1
Also known as: PTP1B
This protein tyrosine phosphatase dephosphorylates key signaling molecules including insulin receptor kinase, EIF2AK3/PERK in the endoplasmic reticulum unfolded protein response, and growth factor receptors. Autosomal dominant mutations cause insulin resistance susceptibility. The gene shows high constraint against loss-of-function variants (pLI 0.81, LOEUF 0.38), indicating that complete loss of function is likely not tolerated.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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.
Literature Evidence
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
59 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 | 1 | 1 | 7 | 0 | 9 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 25 | 1 | 0 | 26 |
Likely Benign | 0 | 3 | 1 | 1 | 5 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 1 | 29 | 12 | 3 | 45 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PTPN1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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