Entrez ID	Official symbol	Synonyms	Description	Location	Type of protein	External annotation
23327	NEDD4L	NEDD4-2, NEDD4.2, PVNH7, RSP5, hNEDD4-2	NEDD4 like E3 ubiquitin protein ligase	18q21.31	protein-coding	Genecard

uniprot_summary

refseq_summary

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, KCNH2, EAAT1 or CLC5 (PubMed:26363003). 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).

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.

Caregory	Description	Value	Value range ( Low - High )	Comment
PLI	The probability of being loss-of-function (LoF) intolerant	1.0	[0, ..., 1]	Genes with high pLI scores (pLI ≥ 0.9) are extremely LoF intolerant, whereby genes with low pLI scores (pLI ≤ 0.1) are LoF tolerant. The score is calculated based on high-quality exome sequence data (ExAC) for 60,706 individuals of diverse ethnicities.
Haploinsufficiency (HI) score rank	Predicted probability of exhibiting haploinsufficiency		[100, ..., 1]	High ranks (e.g. 0-10%) indicate a gene is more likely to exhibit haploinsufficiency, low ranks (e.g. 90-100%) indicate a gene is more likely to NOT exhibit haploinsufficiency (DECIPHER, PMID: 20976243). haploinsufficiency means a single functional copy of a gene is insufficient to maintain its normal function and is extremely intolerant of LoF variation.
Gene brain expressed	Queried gene is expressed in brain tissues	True	[False, True]	The gene expression data are extracted from GTEx v7 and BrainSpan. A gene with the expression value of (log 2 based (TPM+1)) at least 1 TPM/RPKM/FPKM in one or more tissues related to the brain is considered brain-expressed.
Protein brain expressed	Queried protein is expressed in brain tissues	True	[False, True]	The protein expression data are extracted from ProteomicsDB (v2018.09). A protein with the expression value of (log based 10 (iBAQ intensity)) at least 0.5 in one or more tissues related to the brain is considered brain-expressed protein.
Carrying LoF DNMs	Number of loss-of-function DNMs hit the queried gene	0 (Case)	[0, ..., 67] with average of 0.160	Loss of function (LoF) mutations include frameshift indels, nonsense (stop-gained) and splice-site mutations, which can result in the gene product having less or no function and can have deleterious consequences.
		0 (Control)	[0, ..., 6] with average of 0.044
Carrying missense DNMs	Number of missense DNMs hit the queried gene	3 (Case)	[0, ..., 55] with average of 0.846	Missense mutations can result in changes in protein sequences, but are commonly considered to have less deleterious impacts than LoF mutations.
		0 (Control)	[0, ..., 21] with average of 0.300
FMRP binding targets	FMRP inteacting parters	False	[False, True]	FMRP loss of function causes Fragile X syndrome (FXS). The binding targets identified crosslinking immunoprecipitation (HITS-CLIP) in mouse brains (PMID:21784246). Many FMRP targets are among genes implicated in different neuropsychiatric diseases, such as autism, schizophrenia.
Postsynaptic density (PSD)	Protein associates with postsynaptic membranes of excitatory synapses	True	[False, True]	Abnormalities with PSD proteins are linked to various neuropsychiatric diseases including neurodevelopmental disorders.
Human essential genes	-	True	[False, True]	Genes are thought to be critical for human survival.