NEDD4L

Chr 18

NEDD4 like E3 ubiquitin protein ligase

Also known as: NEDD4-2, NEDD4.2, PVNH7, RSP5, hNEDD4-2

NCBI Gene: 23327 ENSG00000049759 UniProt: Q96PU5

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPeriventricular nodular heterotopia 7

Clinical highlights

Gene-disease validity (ClinGen)

periventricular nodular heterotopia 7 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

113

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.20

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)