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Protein / target

Tyrosine-protein phosphatase non-receptor type 1

Encoded byPTPN1P18031Homo sapiensSwiss-Prot
UniProt: P18031Ensembl: ENSG00000196396HGNC: HGNC:9642NCBI Gene: 5770
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine phosphatase

Strongest disease association

Hypothyroidism

Via encoding gene PTPN1 · Genetic evidence · score 0.66

Research activity

Emerging research

1 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response.

View complete UniProt function annotation

Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET

Subcellular location

Endoplasmic reticulum membrane
Domains and Gene Ontology detail (68)

Domains & features

Tyrosine-protein phosphatase

Gene Ontology

  • Ccytoplasm
  • Ccytoplasmic side of endoplasmic reticulum membrane
  • Ccytosol
  • Cearly endosome
  • Cendoplasmic reticulum
  • Cendosome lumen
  • Cglutamatergic synapse
  • Cmitochondrial crista
  • Cmitochondrial matrix
  • Cpostsynapse
  • Cprotein-containing complex
  • Csorting endosome

435 aa · 50 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Growth-factor signallingUniProt · GOSynaptic signallingGOCell proliferation & survivalGOCell migrationGOKinase signallingUniProt · GOApoptosis & cell deathGO
View supporting evidence

Growth-factor signalling

  • ·Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded…
  • ·cellular response to fibroblast growth factor stimulus
  • ·negative regulation of vascular endothelial growth factor receptor signaling pathway
  • ·regulation of hepatocyte growth factor receptor signaling pathway

Synaptic signalling

  • ·glutamatergic synapse
  • ·postsynapse
  • ·regulation of postsynapse assembly

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Cell migration

  • ·negative regulation of vascular associated smooth muscle cell migration

Kinase signalling

  • ·Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded…
  • ·protein kinase binding
  • ·negative regulation of MAP kinase activity
  • ·negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Apoptosis & cell death

  • ·positive regulation of cardiac muscle cell apoptotic process
  • ·positive regulation of endothelial cell apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PTPN1

Gene-level evidence surfaced through the gene PTPN1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hypothyroidism
0.66Moderately supported

Genetic evidence dominant · Open Targets 0.40

Colorectal Neoplasms
0.54Moderately supported

Genetic evidence dominant · Open Targets 0.31

Diabetes Mellitus, Type 1
0.52Moderately supported

Genetic evidence dominant · Open Targets 0.30

Tooth disorder
0.51Moderately supported

Genetic evidence dominant · Open Targets 0.31

Neurodegenerative Diseases
0.36Preliminary

Pathway evidence dominant · Open Targets 0.53 · no direct causal or clinical evidence

View evidence synthesis (5)
HypothyroidismModerately supported
0.66
agreement 0.54–0.78
Genetic100%

Open Targets aggregate 0.40 · 1 independent evidence family

Colorectal NeoplasmsModerately supported
0.54
agreement 0.40–0.67
Genetic83%Literature18%

Open Targets aggregate 0.31 · 2 independent evidence families

Diabetes Mellitus, Type 1Moderately supported
0.52
agreement 0.38–0.66
Genetic81%Literature19%

Open Targets aggregate 0.30 · 2 independent evidence families

Tooth disorderModerately supported
0.51
agreement 0.39–0.63
Genetic100%

Open Targets aggregate 0.31 · 1 independent evidence family

Neurodegenerative DiseasesPreliminary
0.36
agreement 0.18–0.53
Pathway97%Literature4%

Open Targets aggregate 0.53 · 2 independent evidence families · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neurodegenerative Diseases0.53
Alzheimer's Disease0.47
Parkinson's Disease0.47
Multiple Sclerosis0.46
Lysosomal Storage Diseases0.46
Hypothyroidism0.40
Colorectal Neoplasms0.31
Tooth disorder0.31
Diabetes Mellitus, Type 10.30

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.139 cites

Baumgartner CK · Nature · 2023

Recent

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.

Baumgartner CK · Nature · 2023

Europe PMC papers linked directly to this protein.