NKD2
Chr 5NKD inhibitor of Wnt signaling pathway 2
Also known as: Naked2
The protein functions as a negative regulator of canonical Wnt signaling through interaction with Dishevelled proteins and is required for processing and targeting of transforming growth factor alpha to epithelial cell membranes. Mutations cause autosomal dominant developmental delay, intellectual disability, and congenital anomalies with early childhood onset. The gene shows minimal constraint against loss-of-function variants, with some tolerance for such mutations in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
290 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 133 | 0 | 133 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 98 | 23 | 0 | 121 |
Likely Benign | 0 | 11 | 3 | 4 | 18 |
Benign | 0 | 3 | 2 | 0 | 5 |
| Total | 0 | 112 | 163 | 4 | 279 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NKD2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools