NEDD4L
Chr 18ADNEDD4 like E3 ubiquitin protein ligase
Also known as: NEDD4-2, NEDD4.2, PVNH7, RSP5, hNEDD4-2
The protein is a HECT domain E3 ubiquitin ligase that transfers ubiquitin to target proteins for lysosomal degradation and critically regulates epithelial sodium channel (ENaC) cell surface expression to control epithelial sodium transport. Mutations cause periventricular nodular heterotopia 7, inherited in an autosomal dominant pattern. The pathogenic mechanism involves loss of function, as evidenced by the gene's extreme intolerance to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
NEDD4L · 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