DUSP9

Chr X

dual specificity phosphatase 9

Also known as: MKP-4, MKP4

NCBI Gene: 1852ENSG00000130829UniProt: Q99956

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product shows selectivity for members of the ERK family of MAP kinases and is localized to the cytoplasm and nucleus. Aberrant expression of this gene is associated with type 2 diabetes and cancer progression in several cell types. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

197
ClinVar variants
118
Pathogenic / LP
0.82
pLI score
0
Active trials
Clinical Summary— DUSP9
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
118 Pathogenic / Likely Pathogenic· 73 VUS of 197 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.53LOEUF
pLI 0.820
Z-score 2.20
OE 0.00 (0.00–0.53)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.32Z-score
OE missense 0.69 (0.58–0.81)
99 obs / 143.6 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.0.00 (0.00–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.58–0.81)
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.1.00
0≤1.21.6
LoF obs/exp: 0 / 5.7Missense obs/exp: 99 / 143.6Syn Z: 0.02

ClinVar Variant Classifications

197 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
Likely Pathogenic2
VUS73
Likely Benign3
Benign3
116
Pathogenic
2
Likely Pathogenic
73
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
116
0
116
Likely Pathogenic
0
0
2
0
2
VUS
0
54
19
0
73
Likely Benign
0
1
0
2
3
Benign
0
1
0
2
3
Total0561374197

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

View in ClinVar →

Protein Context — Lollipop Plot

DUSP9 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Caffeine ameliorates metabolic-associated steatohepatitis by rescuing hepatic Dusp9.
Xin X et al.·Redox Biol
2025
Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.
Lu H et al.·Cancer Res
2018
Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer by activating JNK signaling.
Wu F et al.·Oncol Rep
2015
Transcriptome fingerprinting of aberrant fibroblast activation unlocks effective therapeutics to tackle cardiac fibrosis.
Cinato M et al.·Sci Adv
2025
Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population.
Binjawhar DN et al.·Genes (Basel)
2023
Dual specificity phosphatase 9 (DUSP9) expression is down-regulated in the severe pre-eclamptic placenta.
Czikk MJ et al.·Placenta
2013
Expression of Dual-Specificity Phosphatase 9 in Placenta and Its Relationship with Gestational Diabetes Mellitus.
Wei Q et al.·J Diabetes Res
2019
Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
Niedzielska M et al.·J Immunol
2015Functional
[Association of DUSP9 gene polymorphisms with gestational diabetes mellitus].
Wang X et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2019
Mutual Exclusion Analysis Shows that DUSP9 Negatively Regulates PD-L1 Expression and Acts as a Target to Enhance Anti-PD-1 Efficacy.
Hu Y et al.·Adv Sci (Weinh)
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools