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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DUSP15
dual specificity phosphatase 15
Chromosome 20 · 20q11.21
NCBI Gene: 128853Ensembl: ENSG00000149599.17HGNC: HGNC:16236UniProt: Q9H1R2
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
dephosphorylationphosphatase activityprotein tyrosine phosphatase activityprotein bindingneurodegenerative diseaseattention deficit hyperactivity disorderhereditary attention deficit-hyperactivity disorderautism
✦AI Summary

DUSP15 (dual specificity phosphatase 15) is a myristoylated phosphatase that plays a critical regulatory role in oligodendrocyte differentiation and myelination. The gene is activated during oligodendrocyte differentiation through cooperative binding of transcription factors Sox10 and Myrf to its promoter 1. DUSP15 regulates oligodendrocyte differentiation by dephosphorylating specific substrates including PDGFR-beta and SNX6 2, and modulates ERK1/2 phosphorylation 3, which is essential for proper myelination in both the central and peripheral nervous systems. Clinically, DUSP15 variants are associated with autism spectrum disorder (ASD) susceptibility. The rs3746599 SNP G/G genotype is significantly associated with decreased ASD risk 4, and the same SNP shows strong association with autism across multiple genetic models 5. A de novo missense variant (p.Ala56Thr) with probable disease-causing effects has been detected in autistic children 5. Additionally, DUSP15 participates in a previously unidentified signaling axis with ERK1/2 and Notch proteins that may influence neuronal differentiation and neurological disease outcomes 3. These findings suggest DUSP15 dysfunction may contribute to developmental neurological disorders through impaired myelination and altered neuronal signaling.

Sources cited
1
Sox10 and Myrf cooperatively activate DUSP15 expression during oligodendrocyte differentiation, and DUSP15 knockdown reduces differentiation markers
PMID: 27532821
2
DUSP15/VHY is transcriptionally regulated during oligodendrocyte differentiation and is a key regulator of OL differentiation; identifies PDGFR-beta and SNX6 as DUSP15 substrates
PMID: 22792334
3
DUSP15 SNP rs3746599 G/G genotype is significantly associated with decreased autism spectrum disorder risk
PMID: 34257739
4
DUSP15 rs3746599 is significantly associated with autism; de novo missense variant p.Ala56Thr detected in autistic child but absent in controls
PMID: 27223645
5
DUSP15 overexpression increases Notch and phosphorylated ERK1/2 levels; reveals DUSP15-ERK1/2-Notch signaling axis relevant to neuronal differentiation and neurological disease
PMID: 33417224
6
DUSP15/VHY is a myristoylated dual specificity phosphatase with membrane localization; related to VHX subfamily; expressed in testis and lower levels in brain and spinal cord
PMID: 15138252
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.29Weak
attention deficit hyperactivity disorderOpen Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.06Suggestive
autismOpen Targets
0.05Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.05Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.05Suggestive
schizophrenia 15Open Targets
0.05Suggestive
Tourette syndromeOpen Targets
0.05Suggestive
Phelan-McDermid syndromeOpen Targets
0.04Suggestive
Potocki-Lupski syndromeOpen Targets
0.03Suggestive
X-linked non-syndromic intellectual disabilityOpen Targets
0.03Suggestive
X-linked dominant intellectual disability - epilepsy syndromeOpen Targets
0.03Suggestive
ovarian neoplasmOpen Targets
0.02Suggestive
frozen shoulderOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
diabetic cardiomyopathyOpen Targets
0.01Suggestive
dilated cardiomyopathyOpen Targets
0.01Suggestive
myeloid sarcomaOpen Targets
0.01Suggestive
multiple sclerosisOpen Targets
0.01Suggestive
chromophobe renal cell carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DUSP23Protein interaction55%DUSP13AShared pathway33%DUSP28Shared pathway33%OPALINShared pathway33%DUSP8Shared pathway33%ALPIShared pathway33%
Tissue Expression6 tissues
Ovary
100%
Heart
50%
Brain
34%
Bone Marrow
26%
Lung
12%
Liver
8%
Gene Interaction Network
Click a node to explore
DUSP15DUSP23DUSP13ADUSP28OPALINDUSP8ALPI
PROTEIN STRUCTURE
Preparing viewer…
PDB1YZ4 · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.50LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.06 [0.76–1.50]
RankingsWhere DUSP15 stands among ~20K protein-coding genes
  • #12,969of 20,598
    Most Researched25
  • #15,170of 17,882
    Most Constrained (LOEUF)1.50
Genes detectedDUSP15
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association between Genetic Variants in
PMID: 34257739
Behav Neurol · 2021
1.00
2
The Dual-specificity phosphatase Dusp15 is regulated by Sox10 and Myrf in Myelinating Oligodendrocytes.
PMID: 27532821
Glia · 2016
0.90
3
Association of oligodendrocytes differentiation regulator gene DUSP15 with autism.
PMID: 27223645
World J Biol Psychiatry · 2017
0.80
4
Dual-Specificity Phosphatase 15 (DUSP15) Modulates Notch Signaling by Enhancing the Stability of Notch Protein.
PMID: 33417224
Mol Neurobiol · 2021
0.70
5
Identification of VHY/Dusp15 as a regulator of oligodendrocyte differentiation through a systematic genomics approach.
PMID: 22792334
PLoS One · 2012
0.60