WNT2

Chr 7

Wnt family member 2

Also known as: INT1L1, IRP

NCBI Gene: 7472ENSG00000105989UniProt: P09544

This gene is a member of the WNT gene family. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

78
ClinVar variants
24
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— WNT2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 51 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.69LOEUF
pLI 0.018
Z-score 2.52
OE 0.35 (0.19–0.69)
Tolerant

Typical tolerance to LoF variation

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.
1.18Z-score
OE missense 0.78 (0.69–0.88)
172 obs / 221.6 exp
Tolerant

Mild missense constraint

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.0.35 (0.19–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.69–0.88)
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.1.00
0≤1.21.6
LoF obs/exp: 6 / 17.3Missense obs/exp: 172 / 221.6Syn Z: -0.01

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS51
Likely Benign1
Benign2
22
Pathogenic
2
Likely Pathogenic
51
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
2
0
2
VUS
0
44
7
0
51
Likely Benign
0
0
0
1
1
Benign
0
1
0
1
2
Total04531278

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

View in ClinVar →

Protein Context — Lollipop Plot

WNT2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell spatial transcriptomics reveals a dynamic control of metabolic zonation and liver regeneration by endothelial cell Wnt2 and Wnt9b.
Hu S et al.·Cell Rep Med
2022
Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids.
Saiki N et al.·Nat Biomed Eng
2025
Functional Insights in PLS3-Mediated Osteogenic Regulation.
Zhong W et al.·Cells
2024Functional
Expression and clinical significance of IL-8 and Wnt2 in Helicobacter pylori-infected gastric cancer patients.
Lin L et al.·J Infect Dev Ctries
2024Cohort
Epithelial WNT secretion drives niche escape of developing gastric cancer.
Lee J et al.·Mol Cancer
2025
The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.
Romanowicz A et al.·Int J Mol Sci
2025Review
Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression.
Kramer N et al.·Oncogene
2017
[Autism, epilepsy and genetics].
Muñoz-Yunta JA et al.·Rev Neurol
2008Review
WNT2B: comparative integromics and clinical applications (Review).
Katoh M·Int J Mol Med
2005Review
Exploring WNT2 polymorphisms in comitant strabismus: A genetic association study.
Zehra Z et al.·Gene
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Nucleosome assembly protein-like 1 degradation-dependent novel cardioprotection mechanism of Wnt2 against ischemia‒reperfusion injury.
Wang Y et al.·Signal Transduct Target Ther
2025🔓 Open AccessFunctional
YY1-mediated transcriptional regulation of LINC01615 inhibits WNT2 mRNA degradation to promote gastric cancer progression.
Lin X et al.·Sci Rep
2025🔓 Open Access
Notch2 improves granulosa cell functions in premature ovarian failure by activating the Wnt2/β-catenin pathway.
Liang X et al.·J Ovarian Res
2025🔓 Open Access
Knockdown of miR-204-5p promotes nerve regeneration and functional recovery after hypoxic-ischemic brain damage in neonatal rats via the Wnt2/Ephrin-A2/EphA7 pathway.
He M et al.·Neuroreport
2025🔓 Open AccessFunctional
m6A modification-dependent upregulation of WNT2 facilitates M2-like macrophage polarization and perpetuates malignant progression of nasopharyngeal carcinoma.
Tang Q et al.·Oncogene
2025
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