WNT16

Chr 7

Wnt family member 16

NCBI Gene: 51384ENSG00000002745UniProt: Q9UBV4

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 contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. [provided by RefSeq, Jul 2008]

76
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— WNT16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 51 VUS of 76 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
1.17LOEUF
pLI 0.000
Z-score 1.07
OE 0.71 (0.45–1.17)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.17Z-score
OE missense 1.03 (0.92–1.16)
215 obs / 208.0 exp
Tolerant

Tolerant to missense variation

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.0.71 (0.45–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.92–1.16)
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.1.03
0≤1.21.6
LoF obs/exp: 11 / 15.5Missense obs/exp: 215 / 208.0Syn Z: -0.21

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS51
Likely Benign4
Benign2
18
Pathogenic
1
Likely Pathogenic
51
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
48
3
0
51
Likely Benign
0
3
1
0
4
Benign
0
1
0
1
2
Total05223176

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

View in ClinVar →

Protein Context — Lollipop Plot

WNT16 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence.
Yu S et al.·Front Immunol
2023
Wnt16 Promotes Vascular Smooth Muscle Contractile Phenotype and Function via Taz (Wwtr1) Activation in Male LDLR-/- Mice.
Behrmann A et al.·Endocrinology
2023
WNT16 elevation induced cell senescence of osteoblasts in ankylosing spondylitis.
Jo S et al.·Arthritis Res Ther
2021
WNT16 as a promising biomarker for systemic lupus erythematosus and its role in regulating cell proliferation and apoptosis.
Wang K et al.·Clin Exp Rheumatol
2024
Non-Canonical Wnt16 and microRNA-145 Mediate the Response of Human Bone Marrow Stromal Cells to Additively Manufactured Porous 3-Dimensional Biomimetic Titanium-Aluminum-Vanadium Constructs.
Cohen DJ et al.·Cells
2025
Effects of WNT3A and WNT16 on the Osteogenic and Adipogenic Differentiation of Perivascular Stem/Stromal Cells.
Shen J et al.·Tissue Eng Part A
2018
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.
Zheng HF et al.·Nature
2015
Induced inactivation of Wnt16 in young adult mice has no impact on osteoarthritis development.
Törnqvist AE et al.·PLoS One
2022
Clinical Characteristics and Pathogenic Gene Identification in Chinese Patients With Paget's Disease of Bone.
Tao X et al.·Front Endocrinol (Lausanne)
2022Cohort
Genetics and Vitamin D Interactions in Osteoporosis: A Path to Precision Medicine.
Abdollahi S et al.·J Cell Mol Med
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
WNT16 Overexpression is Insufficient to Counteract Inflammation-induced Bone Loss in Female Mice.
Nilsson KH et al.·Calcif Tissue Int
2026🔓 Open Access
WNT16 from decidual stromal cells orchestrates M2 macrophage polarization via β-catenin signaling and chromatin remodeling at the maternal-fetal interface.
Chang L et al.·Front Immunol
2025🔓 Open AccessFunctional
The Cys-His-Gly triplet within the WNT motif is essential for Wnt16 function in vivo.
Ramirez EG et al.·MicroPubl Biol
2025🔓 Open Access
Unveiling the Regulatory Mechanism of Tibetan Pigs Adipogenesis Mediated by WNT16: From Differential Phenotypes to the Application of Multi-Omics Approaches.
Huang Q et al.·Animals (Basel)
2025🔓 Open AccessFunctional
Quantification of Wnt3a, Wnt5a and Wnt16 Binding to Multiple Frizzleds Under Physiological Conditions Using NanoBit/BRET.
Wesslowski J et al.·Cells
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools