DVL3

Chr 3AD

dishevelled segment polarity protein 3

Also known as: DRS3

NCBI Gene: 1857ENSG00000161202UniProt: Q92997

This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila dishevelled gene encodes a cytoplasmic phosphoprotein that regulates cell proliferation. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Robinow syndrome, autosomal dominant 3MIM #616894
AD
498
ClinVar variants
59
Pathogenic / LP
0.39
pLI score
0
Active trials
Clinical Summary— DVL3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 215 VUS of 498 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.385
Z-score 4.01
OE 0.22 (0.13–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.32Z-score
OE missense 0.70 (0.65–0.77)
345 obs / 489.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.13–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.65–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 7 / 31.2Missense obs/exp: 345 / 489.4Syn Z: 0.60

ClinVar Variant Classifications

498 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic17
VUS215
Likely Benign166
Benign37
Conflicting21
42
Pathogenic
17
Likely Pathogenic
215
VUS
166
Likely Benign
37
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
33
0
42
Likely Pathogenic
8
1
8
0
17
VUS
13
189
12
1
215
Likely Benign
1
19
44
102
166
Benign
0
13
17
7
37
Conflicting
—21
Total31222114110498

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

View in ClinVar →

Protein Context — Lollipop Plot

DVL3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DVL3-related Robinow syndrome

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
DISHEVELLED 3; DVL3
MIM #601368 · *

Robinow syndrome, autosomal dominant 3

MIM #616894

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — DVL3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
PNPO-Mediated Oxidation of DVL3 Promotes Multiple Myeloma Malignancy and Osteoclastogenesis by Activating the Wnt/β-Catenin Pathway.
Deng Z et al.·Adv Sci (Weinh)
2025
WNT5B promotes the malignant phenotype of non-small cell lung cancer via the FZD3-DVL3-RAC1-PCP-JNK pathway.
Zhao H et al.·Cell Signal
2024
Polymorphism and expression of the Dvl3 gene in the etiology of depressive disorder.
Zajączkowska M et al.·Psychiatr Pol
2020
Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.
Luce A et al.·J Transl Med
2025
E2F7 promotes ESCC progression and cisplatin resistance through transcriptional activation of DVL3 and the Wnt signaling pathway.
Li X et al.·World J Surg Oncol
2025
Silencing DVL3 defeats MTX resistance and attenuates stemness via Notch Signaling Pathway in colorectal cancer.
Zhao Q et al.·Pathol Res Pract
2020
ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.
Kadir R et al.·PLoS Genet
2016
DVL3 Alleles Resulting in a -1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome.
White JJ et al.·Am J Hum Genet
2016
Dishevelled Segment Polarity Protein 3 (DVL3) Induced by Bacterial LPS Promotes the Proliferation and Migration of Prostate Cancer Cells through the TLR4 Pathway.
Zhang Y et al.·Arch Esp Urol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools