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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PTPN12
protein tyrosine phosphatase non-receptor type 12
Chromosome 7 · 7q11.23
NCBI Gene: 5782Ensembl: ENSG00000127947.17HGNC: HGNC:9645UniProt: B4E105
144PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphoprotein phosphatase activityprotein tyrosine phosphatase activityprotein bindingSH3 domain bindingneurodegenerative diseaseAlzheimer diseasemultiple sclerosisParkinson disease
✦AI Summary

PTPN12 (protein tyrosine phosphatase non-receptor type 12) is a cytoplasmic phosphatase that regulates cellular signaling by dephosphorylating tyrosine-phosphorylated proteins. PTPN12 specifically targets key signaling molecules including ERBB2 and PTK2B/PYK2, selectively dephosphorylating ERBB2 at tyrosine residues 1112, 1196, and 1248, thereby modulating ERBB signaling pathways 1. The protein functions as a tumor suppressor gene, with inhibition of its activity leading to uncontrolled cell growth and tumor development 2. In hepatic stellate cells, PTPN12 is regulated by sulfiredoxin-1 through desulfinylation, which enhances its phosphatase activity and protein stability, ultimately inhibiting NLRP3 inflammasome activation and reducing liver fibrosis 3. PTPN12 inactivation in triple-negative breast cancer drives mitotic defects through aberrant hyperactivation of the APC/FZR1 ubiquitin ligase complex, leading to chr7 instability and increased sensitivity to microtubule-targeting agents 4. Additionally, PTPN12 plays roles in osteoarthritis progression through the miR-940/PTPN12 pathway 5 and has been identified as a potential therapeutic target for hypertension 6. These diverse functions highlight PTPN12's importance in regulating cell cycle fidelity, tumor suppression, and inflammatory responses.

Sources cited
1
PTPN12 dephosphorylates ERBB2 and PTK2B/PYK2, selectively targeting ERBB2 at specific tyrosine residues
PMID: 27134172
2
PTPN12 functions as a tumor suppressor gene whose inhibition leads to tumor development
PMID: 32541467
3
PTPN12 is regulated by sulfiredoxin-1 and inhibits NLRP3 inflammasome activation in liver fibrosis
PMID: 39446334
4
PTPN12 inactivation drives mitotic defects and increases taxane sensitivity in triple-negative breast cancer
PMID: 40778818
5
PTPN12 is involved in osteoarthritis progression through the miR-940/PTPN12 pathway
PMID: 35978501
6
PTPN12 has been identified as a potential therapeutic target for hypertension
PMID: 40109242
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.56Moderate
Alzheimer diseaseOpen Targets
0.45Moderate
lysosomal storage diseaseOpen Targets
0.45Moderate
multiple sclerosisOpen Targets
0.45Moderate
Parkinson diseaseOpen Targets
0.45Moderate
hypertensionOpen Targets
0.35Weak
colon carcinomaOpen Targets
0.34Weak
hypertrophic cardiomyopathyOpen Targets
0.33Weak
hypothyroidismOpen Targets
0.31Weak
response to xenobiotic stimulusOpen Targets
0.30Weak
Abnormality of the skeletal systemOpen Targets
0.29Weak
lagophthalmosOpen Targets
0.26Weak
colorectal cancerOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Weak
cancerOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
laryngeal squamous cell carcinomaOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.06Suggestive
Pathogenic Variants1
NM_002835.4(PTPN12):c.182A>G (p.Lys61Arg)Pathogenic
Carcinoma of colon
☆☆☆☆1994→ Residue 61
View on ClinVar ↗
Related Genes
SRCProtein interaction100%PSTPIP1Protein interaction100%PXNProtein interaction99%PTSProtein interaction94%ERBB2Protein interaction94%SHC1Protein interaction93%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
74%
Heart
57%
Ovary
48%
Brain
42%
Liver
30%
Gene Interaction Network
Click a node to explore
PTPN12SRCPSTPIP1PXNPTSERBB2SHC1
PROTEIN STRUCTURE
Preparing viewer…
PDB5HDE · 1.62 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.51Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.34 [0.23–0.51]
RankingsWhere PTPN12 stands among ~20K protein-coding genes
  • #3,170of 20,598
    Most Researched144 · top quartile
  • #4,781of 5,498
    Most Pathogenic Variants1
  • #3,134of 17,882
    Most Constrained (LOEUF)0.51 · top quartile
Genes detectedPTPN12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Progress in the correlation between PTPN12 gene expression and human tumors.
PMID: 32541467
Medicine (Baltimore) · 2020
1.00
2
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
0.90
3
The desulfinylation enzyme sulfiredoxin-1 attenuates HSC activation and liver fibrosis by modulating the PTPN12-NLRP3 axis.
PMID: 39446334
Hepatology · 2025
0.80
4
Integrative Proteogenomics and Forward Genetics Reveal a Novel Mitotic Vulnerability in Triple-Negative Breast Cancer.
PMID: 40778818
Cancer Discov · 2025
0.70
5
Depletion of circ_0128846 ameliorates interleukin-1β-induced human chondrocyte apoptosis and inflammation through the miR-940/PTPN12 pathway.
PMID: 35978501
Int Immunopharmacol · 2022
0.60