WNT3

Chr 17AR

Wnt family member 3

Also known as: INT4, TETAMS

NCBI Gene: 7473ENSG00000108379UniProt: P56703

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Tetra-amelia syndrome 1MIM #273395
AR
UniProtTetraamelia syndrome 1
0
Active trials
10
Pathogenic / LP
153
ClinVar variants
6
Pubs (1 yr)
3.2
Missense Z· constrained
0.40
LOEUF
Clinical Summary— WNT3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 55 VUS of 153 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
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.
0.40LOEUF
pLI 0.875
Z-score 3.19
OE 0.13 (0.05–0.40)
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.
3.18Z-score
OE missense 0.43 (0.37–0.51)
109 obs / 250.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.13 (0.05–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.43 (0.37–0.51)
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.0.93
0≤1.21.6
LoF obs/exp: 2 / 15.6Missense obs/exp: 109 / 250.6Syn Z: 0.59

ClinVar Variant Classifications

153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS55
Likely Benign78
Benign9
Conflicting1
9
Pathogenic
1
Likely Pathogenic
55
VUS
78
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
1
0
0
1
VUS
0
50
4
1
55
Likely Benign
0
0
33
45
78
Benign
0
0
8
1
9
Conflicting
—1
Total0515447153

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

View in ClinVar →

Protein Context — Lollipop Plot

WNT3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

WNT3-related tetra-amelia syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Transport and Secretion of the Wnt3 Ligand by Motor Neuron-like Cells and Developing Motor Neurons
Pinto C et al.·Biomolecules
2021
The Wnt/beta-catenin/TCF/Sp5/Zic4 Gene Network That Regulates Head Organizer Activity in Hydra Is Differentially Regulated in Epidermis and Gastrodermis
Iglesias Ollé L et al.·Biomedicines
2024
Association Analysis of WNT3, HLA-DRB5 and IL1R2 Polymorphisms in Chinese Patients With Parkinson's Disease and Multiple System Atrophy
Su WM et al.·Front Genet
2021Cohort
Silver nanoparticles induce the cardiomyogenic differentiation of bone marrow derived mesenchymal stem cells via telomere length extension
Adibkia K et al.·Beilstein J Nanotechnol
2021
Wnt3 Is Lipidated at Conserved Cysteine and Serine Residues in Zebrafish Neural Tissue
Dhasmana D et al.·Front Cell Dev Biol
2021Functional
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
Therapeutic effects of Lactobacillus rhamnosus, thymol and their combination against neurotoxicity in propionic acid (PA)-induced autistic rats: insights into the role of the Nrf2/HO-1, Wnt3/β-catenin/GSK3β BDNF/p-TrkB/CREB, pI3K/Akt/mTOR, AMPK/SIRT-1, and PERK/CHOP/Bcl-2 pathways.
Salem HA et al.·Front Pharmacol
2025Open Access
Transcriptomics and functional genomics implicate WNT3 in hemispheric lateralization of speech production.
Wang Z et al.·iScience
2026Open AccessFunctional
Impaired WNT3/IGF-1 Signaling in Dorsal Dentate Gyrus Contributes to Chronic Pain-Related Cognitive Impairment.
An Y et al.·CNS Neurosci Ther
2025Open Access
[circ_EPHB4 synergizes with YTHDF3 to promote glioma progression via m6A-dependent stabilization of Wnt3].
Jin C et al.·Nan Fang Yi Ke Da Xue Xue Bao
2025
Extracellular vesicles of cancer cells induce FOXP3+ fibroblasts and facilitate tumor invasion via the Wnt3-β-catenin pathway.
Kimura T et al.·Oncogene
2025
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