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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PTP4A1
protein tyrosine phosphatase 4A1
Chromosome 6 · 6q12
NCBI Gene: 7803Ensembl: ENSG00000112245.14HGNC: HGNC:9634UniProt: Q93096
95PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcytoplasmic side of plasma membranecytoplasmpositive regulation of cell migrationasthmaneurodegenerative diseaseirritable bowel syndromeurinary tract obstruction
✦AI Summary

PTP4A1 is a protein tyrosine phosphatase that plays diverse roles in cellular signaling and disease pathogenesis. In vascular endothelial cells, PTP4A1 functions as an anti-inflammatory regulator by dephosphorylating upstream stimulatory factor 1 (USF1) at residue S309, promoting transcription of TNFAIP3/A20 and subsequent NF-κB pathway inhibition, thereby reducing cell adhesion molecule expression and vascular inflammation 1. In metabolic regulation, hepatic PTP4A1 prevents hepatosteatosis and maintains glucose homeostasis by activating the CREBH/FGF21 axis 2. The protein also regulates peripheral nerve myelination by dephosphorylating cytohesin-2 at Tyr381, with PTP4A1 acting as a negative regulator of myelin thickness in Schwann cells 3. However, PTP4A1 demonstrates oncogenic properties in multiple cancers, promoting cell proliferation, migration, and invasion through interactions with PTEN and activation of PI3K/AKT signaling in intrahepatic cholangiocarcinoma 4, and enhancing TGFβ signaling through SRC-ERK-SMAD3 pathway regulation in systemic sclerosis fibrosis 5. PTP4A1 is frequently targeted by tumor suppressor microRNAs, including miR-1271 in hepatocellular carcinoma 6 and miR-339-5p in glioma 7, highlighting its pathological significance in cancer progression.

Sources cited
1
PTP4A1 dephosphorylates USF1 at S309 to promote A20 transcription and inhibit NF-κB signaling in endothelial cells
PMID: 36534975
2
Hepatic PTP4A1 prevents hepatosteatosis and maintains glucose homeostasis via CREBH/FGF21 axis activation
PMID: 36793871
3
PTP4A1 dephosphorylates cytohesin-2 at Tyr381 and negatively regulates Schwann cell myelination
PMID: 35077201
4
PTP4A1 promotes ICC progression by interacting with PTEN and activating PI3K/AKT/GSK3α signaling
PMID: 40747713
5
PTP4A1 enhances TGFβ signaling through SRC-ERK-SMAD3 pathway in systemic sclerosis fibrosis
PMID: 29057934
6
miR-1271 targets PTP4A1 to inhibit hepatocellular carcinoma metastasis via PTP4A1/c-Src axis
PMID: 29345291
7
miR-339-5p inhibits glioma progression by targeting PTP4A1/HMGB1 pathway
PMID: 35872698
Disease Associationsⓘ20
asthmaOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
irritable bowel syndromeOpen Targets
0.30Weak
urinary tract obstructionOpen Targets
0.26Weak
hypothyroidismOpen Targets
0.22Weak
type 2 diabetes mellitusOpen Targets
0.22Weak
morbid obesityOpen Targets
0.20Weak
diabetes mellitusOpen Targets
0.17Weak
autoimmune disorder of musculoskeletal systemOpen Targets
0.16Weak
intrahepatic cholangiocarcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
retinitis pigmentosaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
lower respiratory tract diseaseOpen Targets
0.08Suggestive
major depressive disorderOpen Targets
0.07Suggestive
systemic sclerodermaOpen Targets
0.07Suggestive
cervical cancerOpen Targets
0.07Suggestive
schizophreniaOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARHGEF39Shared pathway100%CNNM2Protein interaction97%ATF7Protein interaction92%PTP4A2Protein interaction90%PTSProtein interaction84%PHF3Protein interaction80%
Tissue Expression6 tissues
Liver
100%
Brain
30%
Lung
19%
Ovary
13%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
PTP4A1ARHGEF39CNNM2ATF7PTP4A2PTSPHF3
PROTEIN STRUCTURE
Preparing viewer…
PDB1RXD · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.80LoF Tolerant
pLIⓘ
0.24Tolerant
Observed/Expected LoF0.43 [0.24–0.80]
RankingsWhere PTP4A1 stands among ~20K protein-coding genes
  • #5,054of 20,598
    Most Researched95 · top quartile
  • #6,693of 17,882
    Most Constrained (LOEUF)0.80
Genes detectedPTP4A1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation.
PMID: 36534975
Cardiovasc Res · 2023
1.00
2
PTP4A1 promotes intrahepatic cholangiocarcinoma development and progression by interacting with PTEN and activating the PI3K/AKT/GSKα axis.
PMID: 40747713
Oncol Rep · 2025
0.90
3
GINS2 promotes oral squamous cell carcinoma progression and immune evasion by recruiting PD-L1
PMID: 41322418
Front Immunol · 2025
0.80
4
Hepatic PTP4A1 ameliorates high-fat diet-induced hepatosteatosis and hyperglycemia by the activation of the CREBH/FGF21 axis.
PMID: 36793871
Theranostics · 2023
0.70
5
The adaptor SH2B1 and the phosphatase PTP4A1 regulate the phosphorylation of cytohesin-2 in myelinating Schwann cells in mice.
PMID: 35077201
Sci Signal · 2022
0.60