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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DVL3
dishevelled segment polarity protein 3
Chromosome 3 Β· 3q27.1
NCBI Gene: 1857Ensembl: ENSG00000161202.21HGNC: HGNC:3087UniProt: Q92997
154PubMed Papers
21Diseases
0Drugs
19Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protease bindingsignaling receptor bindingfrizzled bindingprotein bindingautosomal dominant Robinow syndromeRobinow syndromeShort statureMidface retrusion
✦AI Summary

DVL3 (dishevelled segment polarity protein 3) is a core component of Wnt signaling pathways that functions as a membrane-associated protein propagating WNT signals from the cell membrane to the nucleus 1. DVL3 regulates multiple cellular processes including canonical and non-canonical Wnt/Ξ²-catenin signaling, planar cell polarity (PCP) pathways, and JNK cascade activation 2. Nuclear localization of DVL3 is essential for its function in regulating cell proliferation, requiring both its DIX and PDZ domains 1. Mechanistically, DVL3 activation occurs through frizzled receptor-mediated recruitment to the cell membrane, where it undergoes phosphorylation and activates downstream effectors including RAC1 and JNK signaling 2. Post-translational modification of DVL3 through PNPO-mediated oxidation promotes aberrant Wnt/Ξ²-catenin pathway activation 3. DVL3 dysregulation is implicated in multiple diseases. Robinow syndrome, autosomal dominant 3 results from DVL3 mutations. DVL3 overexpression promotes malignancy in multiple myeloma, non-small cell lung cancer, esophageal squamous cell carcinoma, and glioblastoma, correlating with advanced tumor stage and poor prognosis 3, 2, 4, 5. Additionally, decreased DVL3 expression associates with depressive disorder risk, with rs1969253 polymorphism conferring 3.3-fold increased depression susceptibility 6. In rheumatoid arthritis, exosomal DVL3 promotes fibroblast-like synovial cell aggression via Wnt pathway activation 7.

Sources cited
1
DVL3 is a membrane-associated protein that propagates WNT signaling; requires nuclear localization via DIX and PDZ domains to regulate proliferation in myoblasts
PMID: 35589804
2
DVL3 is recruited to the membrane via FZD3 receptor in a WNT5B-dependent manner and activates RAC1-PCP-JNK signaling through its DEP domain in NSCLC
PMID: 39094673
3
PNPO-mediated oxidation of DVL3 at M282 promotes multiple myeloma malignancy by activating the Wnt/Ξ²-catenin pathway
PMID: 39656865
4
DVL3 overexpression promotes proliferation, migration, and tumor formation in esophageal squamous cell carcinoma; associates with invasion and metastasis
PMID: 30536315
5
DVL3 shows strong expression in glioblastoma and localizes to both cytoplasm and nucleus, correlating with aggressive tumor characteristics
PMID: 29200599
6
DVL3 mRNA and protein levels are decreased in depression; rs1969253 polymorphism (CA/CC genotypes) confers 3.3-fold increased depression risk
PMID: 33038884
7
Exosomal DVL3 promotes rheumatoid arthritis fibroblast-like synovial cell aggression through Wnt/Ξ²-catenin pathway activation
PMID: 35499309
8
DVL3 mutations are associated with congenital disorders of autophagy presenting with neurodevelopmental and neurodegenerative manifestations
PMID: 34130600
Disease Associationsβ“˜21
autosomal dominant Robinow syndromeOpen Targets
0.73Strong
Robinow syndromeOpen Targets
0.72Strong
Anteverted naresOpen Targets
0.26Weak
Clinodactyly of the 5th fingerOpen Targets
0.26Weak
Dental crowdingOpen Targets
0.26Weak
Genu valgumOpen Targets
0.26Weak
Lumbar hyperlordosisOpen Targets
0.26Weak
Midface retrusionOpen Targets
0.26Weak
Neurodevelopmental delayOpen Targets
0.26Weak
Short fingerOpen Targets
0.26Weak
Short statureOpen Targets
0.26Weak
Short toeOpen Targets
0.26Weak
Tented upper lip vermilionOpen Targets
0.26Weak
diabetic neuropathyOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
alcohol drinkingOpen Targets
0.16Weak
hypertensionOpen Targets
0.16Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
Robinow syndrome, autosomal dominant 3UniProt
Pathogenic Variants19
NM_004423.4(DVL3):c.1715-1G>APathogenic
Autosomal dominant Robinow syndrome 1|Autosomal dominant Robinow syndrome 3|Autosomal dominant Robinow syndrome 2
β˜…β˜…β˜†β˜†2022
NM_004423.4(DVL3):c.1672_1705del (p.Tyr558fs)Pathogenic
Autosomal dominant Robinow syndrome 3
β˜…β˜†β˜†β˜†2024β†’ Residue 558
NM_004423.4(DVL3):c.1688dup (p.Ser564fs)Likely pathogenic
Autosomal dominant Robinow syndrome 3
β˜…β˜†β˜†β˜†2023β†’ Residue 564
NM_004423.4(DVL3):c.1760_1763del (p.Lys587fs)Likely pathogenic
See cases
β˜…β˜†β˜†β˜†2020β†’ Residue 587
NM_004423.4(DVL3):c.1473C>G (p.Tyr491Ter)Likely pathogenic
Autosomal dominant Robinow syndrome 3
β˜…β˜†β˜†β˜†2020β†’ Residue 491
NM_004423.4(DVL3):c.1751_1754del (p.Asp584fs)Pathogenic
not provided|Autosomal dominant Robinow syndrome 3
β˜…β˜†β˜†β˜†2018β†’ Residue 584
NM_004423.4(DVL3):c.1728_1752del (p.Ser578fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 578
NM_004423.4(DVL3):c.1592del (p.Pro531fs)Pathogenic
Autosomal dominant Robinow syndrome 3
β˜…β˜†β˜†β˜†2017β†’ Residue 531
NM_004423.4(DVL3):c.1617del (p.Gln539fs)Likely pathogenic
Autosomal dominant Robinow syndrome 2
β˜…β˜†β˜†β˜†2017β†’ Residue 539
NM_004423.4(DVL3):c.1745del (p.Gly582fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 582
NM_004423.4(DVL3):c.1715-2A>GPathogenic
Autosomal dominant Robinow syndrome 1|Autosomal dominant Robinow syndrome 3|Autosomal dominant Robinow syndrome 2
β˜…β˜†β˜†β˜†2015
NM_004423.4(DVL3):c.1716del (p.Ser573fs)Pathogenic
Autosomal dominant Robinow syndrome 1|Autosomal dominant Robinow syndrome 3|Autosomal dominant Robinow syndrome 2
β˜…β˜†β˜†β˜†2015β†’ Residue 573
NM_004423.4(DVL3):c.1749del (p.Ser583fs)Pathogenic
Autosomal dominant Robinow syndrome 1|Autosomal dominant Robinow syndrome 3|Autosomal dominant Robinow syndrome 2
β˜…β˜†β˜†β˜†2015β†’ Residue 583
NM_004423.4(DVL3):c.1585del (p.Ala529fs)Pathogenic
Autosomal dominant Robinow syndrome 1|Autosomal dominant Robinow syndrome 3|Autosomal dominant Robinow syndrome 2
β˜…β˜†β˜†β˜†2015β†’ Residue 529
NM_004423.4(DVL3):c.1715-2A>CPathogenic
Autosomal dominant Robinow syndrome 1
β˜…β˜†β˜†β˜†
NM_004423.4(DVL3):c.292del (p.Glu98fs)Likely pathogenic
Autosomal dominant Robinow syndrome 3
β˜†β˜†β˜†β˜†2023β†’ Residue 98
NM_004423.4(DVL3):c.1715-2delLikely pathogenic
Autosomal dominant Robinow syndrome 3
β˜†β˜†β˜†β˜†2020
NM_004423.4(DVL3):c.1715-1G>CLikely pathogenic
Autosomal dominant Robinow syndrome 3
β˜†β˜†β˜†β˜†2019
NM_004423.4(DVL3):c.367G>A (p.Gly123Arg)Likely pathogenic
11 conditions
β˜†β˜†β˜†β˜†β†’ Residue 123
View on ClinVar β†—
Related Genes
AXIN1Protein interaction100%VANGL2Protein interaction99%LRP6Protein interaction99%ADARProtein interaction99%APCProtein interaction99%CSNK1DProtein interaction99%
Tissue Expression6 tissues
Ovary
100%
Heart
97%
Lung
84%
Brain
63%
Liver
53%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
DVL3AXIN1VANGL2LRP6ADARAPCCSNK1D
PROTEIN STRUCTURE
Preparing viewer…
PDB8S6A Β· 1.36 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.54Moderately Constrained
pLIβ“˜
0.70Intermediate
Observed/Expected LoF0.39 [0.29–0.54]
RankingsWhere DVL3 stands among ~20K protein-coding genes
  • #2,935of 20,598
    Most Researched154 Β· top quartile
  • #2,228of 5,498
    Most Pathogenic Variants19
  • #3,367of 17,882
    Most Constrained (LOEUF)0.54 Β· top quartile
Genes detectedDVL3
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
DVL1 and DVL3 require nuclear localisation to regulate proliferation in human myoblasts.
PMID: 35589804
Sci Rep Β· 2022
1.00
2
PNPO-Mediated Oxidation of DVL3 Promotes Multiple Myeloma Malignancy and Osteoclastogenesis by Activating the Wnt/Ξ²-Catenin Pathway.
PMID: 39656865
Adv Sci (Weinh) Β· 2025
0.90
3
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
PMID: 34130600
Autophagy Β· 2022
0.80
4
Polymorphism and expression of the Dvl3 gene in the etiology of depressive disorder.
PMID: 33038884
Psychiatr Pol Β· 2020
0.70
5
[Wnt Signaling and Skeletal Dysplasias.].
PMID: 30814377
Clin Calcium Β· 2019
0.68