NEDD4L

Chr 18q21.31

NEDD4 like E3 ubiquitin protein ligase

Aliases:: KIAA0439, RSP5, NEDD4-2
MANE:: ENST00000400345.8

OMIM: 606384 ↗NCBI: 23327 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

NEDD4L · Q96PU5

v62025-08-01

Predicted Aligned Error matrix for NEDD4L — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

68.4/ 100

Low

975 residues

Confidence breakdown

Very high(≥ 90)29%
Confident(70–90)29%
Low(50–70)10%
Very low(< 50)32%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Clefting
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

periventricular nodular heterotopia
0.75
periventricular nodular heterotopia 7
0.75
HIV infectious disease
0.46
atrial fibrillation
0.37
cleft palate
0.37
mathematical ability
0.35
hypertensive disorder
0.34
dilated cardiomyopathy
0.33
cancer
0.33
essential hypertension
0.33

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

E3 ubiquitin-protein ligase NEDD4-like

E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:20064473, PubMed:31959741, PubMed:33608556). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556). Ubiquitinates TTYH2 and TTYH3 and regulates protein levels of TTYH2 (PubMed:18577513)