DUSP15

Chr 20

dual specificity phosphatase 15

Also known as: C20orf57, VHY

NCBI Gene: 128853ENSG00000149599UniProt: Q9H1R2

This dual specificity phosphatase dephosphorylates multiple proteins including MAP kinases and growth factor receptors, and may function in oligodendrocyte differentiation. Mutations cause autosomal recessive intellectual disability with neurodegeneration and brain atrophy. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected families.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
1.50
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DUSP15
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 57 VUS of 90 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — DUSP15
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.50LOEUF
pLI 0.000
Z-score 0.41
OE 0.86 (0.52–1.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.40Z-score
OE missense 1.10 (0.96–1.27)
132 obs / 119.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.52–1.50)
0≤0.351.4
Missense OE1.10 (0.96–1.27)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 9 / 10.4Missense obs/exp: 132 / 119.8Syn Z: -0.51
DN
0.6938th %ile
GOF
0.80top 10%
LOF
0.3259th %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

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS57
Likely Benign4
10
Pathogenic
6
Likely Pathogenic
57
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
6
0
6
VUS
1
49
7
0
57
Likely Benign
0
1
3
0
4
Benign
0
0
0
0
0
Total15026077

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

View in ClinVar →

Protein Context — Lollipop Plot

DUSP15 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy.
Liu Y et al.·Cardiovasc Diabetol
2026
DUSP15 exhibits structural and dynamical signatures inconsistent with catalytic phosphatase activity.
Sarhan AR.·Biochim Biophys Acta Proteins Proteom
2026
Murine Model Insights: Identifying Dusp15 as a Novel Biomarker for Diabetic Cardiomyopathy Uncovered Through Integrated Omics Analysis and Experimental Validation.
Zhu L et al.·Diabetes Metab Syndr Obes
2025Functional
The Atypical Dual Specificity Phosphatase DUSP15 Regulates Jak1-Mediated STAT3 Activation.
Kikkawa K et al.·Biol Pharm Bull
2024
DUSP15 expression is reduced in the hippocampus of Myrf knock-out mice but attention and object recognition memory remain intact.
Rawlings-Mortimer F et al.·PLoS One
2023Open Access
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