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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DVL2
dishevelled segment polarity protein 2
Chromosome 17 · 17p13.1
NCBI Gene: 1856Ensembl: ENSG00000004975.13HGNC: HGNC:3086UniProt: O14641
220PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
frizzled bindingprotein bindingidentical protein bindingregulation of DNA-templated transcriptionRobinow syndromepelvic organ prolapsecolorectal carcinomabreast cancer
✦AI Summary

DVL2 (dishevelled segment polarity protein 2) is a key intracellular mediator of both canonical and non-canonical Wnt signaling pathways 1. DVL2 functions by binding to frizzled receptors and transducing Wnt signals to downstream effectors, particularly promoting β-catenin nuclear translocation through phosphorylation at serine 675 1. The protein undergoes extensive post-translational regulation, including phosphorylation by multiple kinases and dephosphorylation by phosphatases such as PP5 (PPP5C) 2. DVL2 stability is regulated through ubiquitination mechanisms, with WWP1-mediated K27-linked ubiquitination stabilizing the protein 3 and WWP2-mediated K63-linked ubiquitination promoting liquid-liquid phase separation critical for Wnt signaling 4. Clinically, DVL2 variants are associated with Robinow syndrome, a skeletal dysplasia disorder affecting WNT/planar cell polarity signaling 5. DVL2 polymorphisms have also been linked to increased risk of nonsyndromic cleft lip with or without cleft palate 6. The protein plays roles in cardiac hypertrophy through the DVL2/CaMKII/HDAC4/MEF2C pathway 3 and is involved in macrophage polarization via β-catenin signaling 7.

Sources cited
1
DVL2 is a key mediator of canonical and non-canonical Wnt signaling, promoting β-catenin nuclear translocation
PMID: 40973792
2
PP5 is a phosphatase that dephosphorylates DVL2 at multiple sites including S143
PMID: 29426949
3
WWP1-mediated K27-linked ubiquitination stabilizes DVL2 and contributes to cardiac hypertrophy
PMID: 34139860
4
WWP2-mediated K63-linked ubiquitination promotes DVL2 phase separation essential for Wnt signaling
PMID: 36398662
5
DVL2 variants are associated with Robinow syndrome affecting WNT/planar cell polarity signaling
PMID: 35047859
6
DVL2 polymorphisms are associated with increased risk of nonsyndromic cleft lip with or without cleft palate
PMID: 22887353
7
DVL2 is involved in macrophage polarization via β-catenin signaling pathway
PMID: 38433252
Disease Associationsⓘ20
Robinow syndromeOpen Targets
0.42Moderate
pelvic organ prolapseOpen Targets
0.14Weak
colorectal carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
rheumatoid arthritisOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
hearing lossOpen Targets
0.06Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
Abnormality of the skeletal systemOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
Heart defects - limb shorteningOpen Targets
0.04Suggestive
heart defects-limb shortening syndromeOpen Targets
0.04Suggestive
autosomal recessive spondylocostal dysostosisOpen Targets
0.04Suggestive
spondylocostal dysostosis 4, autosomal recessiveOpen Targets
0.04Suggestive
pyknoachondrogenesisOpen Targets
0.04Suggestive
Holt-Oram syndromeOpen Targets
0.04Suggestive
vertebral, cardiac, renal, and limb defects syndrome 3Open Targets
0.04Suggestive
Lung agenesis - heart defect - thumb anomaliesOpen Targets
0.04Suggestive
lung agenesis-heart defect-thumb anomalies syndromeOpen Targets
0.04Suggestive
isolated Klippel-Feil syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AXIN1Protein interaction100%VANGL1Protein interaction99%LRP6Protein interaction99%DACT1Protein interaction99%ARRB2Protein interaction98%WNT5AProtein interaction98%
Tissue Expression6 tissues
Ovary
100%
Lung
46%
Bone Marrow
45%
Heart
44%
Brain
39%
Liver
33%
Gene Interaction Network
Click a node to explore
DVL2AXIN1VANGL1LRP6DACT1ARRB2WNT5A
PROTEIN STRUCTURE
Preparing viewer…
PDB3CBZ · 1.38 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.55 [0.42–0.72]
RankingsWhere DVL2 stands among ~20K protein-coding genes
  • #1,867of 20,598
    Most Researched220 · top 10%
  • #5,532of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedDVL2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis.
PMID: 38433252
Bone Res · 2024
1.00
2
Targeting E3 Ubiquitin Ligase WWP1 Prevents Cardiac Hypertrophy Through Destabilizing DVL2 via Inhibition of K27-Linked Ubiquitination.
PMID: 34139860
Circulation · 2021
0.90
3
RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma.
PMID: 38576051
J Exp Clin Cancer Res · 2024
0.80
4
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
0.80
5
ASPM promotes hepatocellular carcinoma progression by activating Wnt/β-catenin signaling through antagonizing autophagy-mediated Dvl2 degradation.
PMID: 34428354
FEBS Open Bio · 2021
0.76