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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DUSP12
dual specificity phosphatase 12
Chromosome 1 · 1q23.3
NCBI Gene: 11266Ensembl: ENSG00000081721.13HGNC: HGNC:3067UniProt: Q9UNI6
43PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusnucleoplasmcytoplasmprotein bindingneurodegenerative diseaseneuroinflammatory disorderHepatic steatosishepatocellular carcinoma
✦AI Summary

DUSP12 (dual specificity phosphatase 12) is an atypical dual-specificity phosphatase that dephosphorylates both tyrosine and serine/threonine residues on target proteins 1. The protein contains a unique zinc-binding domain in addition to its catalytic domain, making it one of the largest DUSPs with strong nuclear expression 2. DUSP12 regulates multiple cellular processes including cell cycle progression, apoptosis protection, and stress responses. Mechanistically, DUSP12 interacts with and dephosphorylates ZPR9 at Ser143, promoting cell cycle progression and protecting cells from stress-induced apoptosis 1. In cardiac tissue, DUSP12 ameliorates pathological hypertrophy by inhibiting JNK1/2 activity, with decreased expression observed in hypertrophic hearts 3. The protein also regulates mTORC1/S6 signaling by blocking DUSP12-mediated dephosphorylation of p-S6 (S235/236) in cancer contexts 4. Disease relevance includes potential roles in systemic lupus erythematosus as a biomarker 5, cardiovascular protection through anti-inflammatory and anti-oxidative stress mechanisms 6, and oncogenic properties including increased cell motility and apoptosis resistance 7. DUSP12's nuclear interaction networks connect it to cytoskeletal regulation, chr1 modification, and ribosome maturation 2.

Sources cited
1
DUSP12 dephosphorylates both tyrosine and serine/threonine residues and interacts with ZPR9 to regulate cell cycle and apoptosis
PMID: 39868293
2
DUSP12 contains a zinc-binding domain, is one of the largest DUSPs with nuclear expression, and has interaction networks involving cytoskeleton and chromatin
PMID: 30779967
3
DUSP12 ameliorates cardiac hypertrophy by inhibiting JNK1/2 activity and is downregulated in hypertrophic hearts
PMID: 27702885
4
DUSP12 regulates mTORC1/S6 signaling by blocking dephosphorylation of p-S6 (S235/236)
PMID: 40135815
5
DUSP12 is involved in autoimmune diseases including systemic lupus erythematosus as a potential biomarker
PMID: 31766293
6
DUSP12 provides cardiovascular protection through anti-inflammatory and anti-oxidative stress mechanisms
PMID: 37614418
7
DUSP12 overexpression confers oncogenic properties including increased cell motility and apoptosis resistance
PMID: 21556130
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.49Moderate
neuroinflammatory disorderOpen Targets
0.17Weak
Hepatic steatosisOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
functional neutrophil defectOpen Targets
0.04Suggestive
liver cancerOpen Targets
0.04Suggestive
alcohol drinkingOpen Targets
0.03Suggestive
neutropeniaOpen Targets
0.03Suggestive
acute lung injuryOpen Targets
0.03Suggestive
chordomaOpen Targets
0.03Suggestive
Decreased total leukocyte countOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
bacterial diseaseOpen Targets
0.02Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.02Suggestive
cardiac hypertrophyOpen Targets
0.02Suggestive
neuroblastomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
non-alcoholic steatohepatitisOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
synovial sarcomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
JUNProtein interaction100%MAPK14Protein interaction100%MAPK3Protein interaction99%FOSProtein interaction99%FOSBProtein interaction78%MRTO4Protein interaction78%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
42%
Lung
35%
Brain
29%
Liver
28%
Heart
24%
Gene Interaction Network
Click a node to explore
DUSP12JUNMAPK14MAPK3FOSFOSBMRTO4
PROTEIN STRUCTURE
Preparing viewer…
PDB4KI9 · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.49–0.94]
RankingsWhere DUSP12 stands among ~20K protein-coding genes
  • #9,722of 20,598
    Most Researched43
  • #8,815of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedDUSP12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RAB3B Dictates mTORC1/S6 Signaling in Chordoma and Predicts Response to mTORC1-Targeted Therapy.
PMID: 40135815
Adv Sci (Weinh) · 2025
1.00
2
MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus.
PMID: 31766293
Cells · 2019
0.90
3
Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload.
PMID: 27702885
Clin Sci (Lond) · 2017
0.80
4
DUSP12 promotes cell cycle progression and protects cells from cell death by regulating ZPR9.
PMID: 39868293
bioRxiv · 2025
0.70
5
FOXP1‑induced DUSP12 alleviates vascular endothelial cell inflammation and oxidative stress injury induced by ox‑LDL via MAP3K5 signaling pathway.
PMID: 37614418
Exp Ther Med · 2023
0.60