PTPN12

Chr 7

protein tyrosine phosphatase non-receptor type 12

Also known as: PTP-PEST, PTPG1

NCBI Gene: 5782ENSG00000127947UniProt: Q05209

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein-protein interaction domain, and may regulate protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of the oncogene c-ABL and thus may play a role in oncogenesis. This PTP was also shown to interact with, and dephosphorylate, various products related to cytoskeletal structure and cell adhesion, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin. This suggests it has a regulatory role in controlling cell shape and mobility. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Colon cancer, somaticMIM #114500
117
ClinVar variants
16
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PTPN12
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 86 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 5.56
OE 0.07 (0.03–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.16Z-score
OE missense 0.84 (0.76–0.92)
330 obs / 394.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.76–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 3 / 41.7Missense obs/exp: 330 / 394.7Syn Z: -0.93

ClinVar Variant Classifications

117 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS86
Likely Benign10
Benign5
15
Pathogenic
1
Likely Pathogenic
86
VUS
10
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
14
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
78
8
0
86
Likely Benign
0
2
2
6
10
Benign
0
3
1
1
5
Total084267117

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PTPN12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Colon cancer, somatic

MIM #114500

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
Monies D et al.·Hum Genet
2017
Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma.
Jin Y et al.·J Int Med Res
2020
Update on enthesitis-related arthritis.
Weiss PF·Curr Opin Rheumatol
2016Review
DUSP14 suppresses ferroptosis and promotes tumor progression of triple-negative breast cancer.
Cao Y et al.·Cell Rep
2025
PTPN12 inhibits oral squamous epithelial carcinoma cell proliferation and invasion and can be used as a prognostic marker.
Su Z et al.·Med Oncol
2013
A missense variant in PTPN12 associated with the risk of colorectal cancer by modifying Ras/MEK/ERK signaling.
Shen N et al.·Cancer Epidemiol
2019
Spatially interacting phosphorylation sites and mutations in cancer.
Huang KL et al.·Nat Commun
2021
The prognostic significance of tyrosine-protein phosphatase nonreceptor type 12 expression in nasopharyngeal carcinoma.
Zhang XK et al.·Tumour Biol
2015
Identifying the role of PTPN12 expression in predicting the efficacy of capecitabine to neoadjuvant chemotherapy in breast cancer treatment.
Wang YY et al.·Eur Rev Med Pharmacol Sci
2016
Decreased expression of PTPN12 correlates with tumor recurrence and poor survival of patients with hepatocellular carcinoma.
Luo RZ et al.·PLoS One
2014Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
miR-194-5p-mediated suppression of protein tyrosine phosphatase non-receptor type 12 (PTPN12) expression in the thymus enhances immunologic functional restoration in aged mice.
Ai LY et al.·Eur J Med Res
2026🔓 Open AccessFunctional
miR-369-3p regulates the drug resistance of lung cancer cells by targeting PTPN12.
Wang Y et al.·Pharmacogenomics
2025
Biochemical and Structural Studies of Protein Tyrosine Phosphatase PTP-PEST (PTPN12) in Search of Small Molecule Inhibitors.
Johnson D et al.·Chem Biol Drug Des
2025
The desulfinylation enzyme sulfiredoxin-1 attenuates HSC activation and liver fibrosis by modulating the PTPN12-NLRP3 axis.
Kim JW et al.·Hepatology
2025
Erratum to Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway.
Editorial Office.·Ann Transl Med
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools