Entrez ID	Official symbol	Synonyms	Description	Location	Type of protein	External annotation
80762	NDFIP1	N4WBP5	Nedd4 family interacting protein 1	5q31.3	protein-coding	Genecard

uniprot_summary

refseq_summary

Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (By similarity). Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551). Restricts the production of proinflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC (By similarity). Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (By similarity). Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (By similarity). Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (PubMed:23087404). Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation (PubMed:26363003). In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity (PubMed:19706893). Important for normal development of dendrites and dendritic spines in cortex (By similarity). Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (By similarity). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (PubMed:20534535). Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959).

The protein encoded by this gene belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. It is a potential target for ubiquitination by the Nedd4 family of proteins. This protein is thought to be part of a family of integral Golgi membrane proteins.

Caregory	Description	Value	Value range ( Low - High )	Comment
PLI	The probability of being loss-of-function (LoF) intolerant	0.92	[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	0 (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	False	[False, True]	Abnormalities with PSD proteins are linked to various neuropsychiatric diseases including neurodevelopmental disorders.
Human essential genes	-	False	[False, True]	Genes are thought to be critical for human survival.