DUSP2

Chr 2

dual specificity phosphatase 2

Also known as: PAC-1, PAC1

NCBI Gene: 1844ENSG00000158050UniProt: Q05923

DUSP2 encodes a dual specificity phosphatase that dephosphorylates and inactivates ERK1 and ERK2 MAP kinases, negatively regulating cellular proliferation and differentiation pathways. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly. The gene shows very low constraint to loss-of-function variants (pLI 0.00004), suggesting tolerance to complete loss of function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
18
Pubs (1 yr)
31
P/LP submissions
0%
P/LP missense
1.61
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DUSP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 93 VUS of 134 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.61LOEUF
pLI 0.000
Z-score 0.31
OE 0.88 (0.50–1.61)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.08Z-score
OE missense 0.98 (0.86–1.13)
146 obs / 148.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.88 (0.50–1.61)
0≤0.351.4
Missense OE0.98 (0.86–1.13)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 7 / 7.9Missense obs/exp: 146 / 148.9Syn Z: 0.42
DN
0.7035th %ile
GOF
0.72top 25%
LOF
0.2775th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic10
VUS93
Likely Benign4
Benign1
21
Pathogenic
10
Likely Pathogenic
93
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
10
0
10
VUS
0
59
34
0
93
Likely Benign
0
0
3
1
4
Benign
0
0
0
1
1
Total059682129

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

View in ClinVar →

Protein Context — Lollipop Plot

DUSP2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
MiR-106a-5p in extracellular vesicles derived from alveolar epithelial cells mediates cognitive dysfunction induced by chronic intermittent hypoxia in mice through MAPK signaling pathway
Wang B et al.·J Neuroinflammation
2025
Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer
Yang G et al.·Front Oncol
2023
Bioinformatic analysis and experimental validation of the potential gene in the airway inflammation of steroid-resistant asthma
Wei C et al.·Sci Rep
2023
DUSP2 deletion with CRISPR/Cas9 promotes Mauthner cell axonal regeneration at the early stage of zebrafish
Shao GJ et al.·Neural Regen Res
2023Functional
Identification of clinical diagnostic and immune cell infiltration characteristics of acute myocardial infarction with machine learning approach
Jiang H et al.·Sci Rep
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients