DVL2

Chr 17

dishevelled segment polarity protein 2

NCBI Gene: 1856ENSG00000004975UniProt: O14641OMIM: 602151

This protein functions as a cytoplasmic signal transducer in Wnt signaling pathways, binding to frizzled receptors and transmitting signals to downstream effectors in both canonical and non-canonical pathways. Mutations cause autosomal dominant neurodevelopmental disorders characterized by intellectual disability, autism spectrum disorder, and brain malformations. The gene is moderately constrained against loss-of-function variants, consistent with its essential role in early brain development.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.66
Clinical Summary— DVL2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 117 VUS of 182 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.000
Z-score 3.10
OE 0.42 (0.28–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.32Z-score
OE missense 0.96 (0.89–1.04)
447 obs / 466.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.28–0.66)
0≤0.351.4
Missense OE0.96 (0.89–1.04)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 14 / 33.3Missense obs/exp: 447 / 466.6Syn Z: -1.14
DN
0.7326th %ile
GOF
0.6639th %ile
LOF
0.4332th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

182 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic7
VUS117
Likely Benign12
Benign10
26
Pathogenic
7
Likely Pathogenic
117
VUS
12
Likely Benign
10
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
2
2
3
0
7
VUS
0
107
10
0
117
Likely Benign
0
4
4
4
12
Benign
0
2
4
4
10
Total2115478172

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

View in ClinVar →

Protein Context — Lollipop Plot

DVL2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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