N4BP3

Summary

N4BP3 (NEDD4 binding protein 3, HGNC:29852) is a protein-coding gene on chromosome 5q35.3, encoding NEDD4-binding protein 3 (O15049). Plays a positive role in the antiviral innate immune signaling pathway.

Acts upstream of with a positive effect on innate immune response. Predicted to be located in axon and dendrite. Predicted to be active in cytoplasmic vesicle.

Source: NCBI Gene 23138 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 143 total
• MANE Select transcript: NM_015111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29852
Approved symbol	N4BP3
Name	NEDD4 binding protein 3
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	LZTS4
Ensembl gene	ENSG00000145911
Ensembl biotype	protein_coding
OMIM	619140
Entrez	23138

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

ENST00000274605, ENST00000850869, ENST00000878585, ENST00000878586, ENST00000878587, ENST00000933261, ENST00000933262, ENST00000933263, ENST00000933264, ENST00000933265, ENST00000933266, ENST00000933267, ENST00000933268, ENST00000933269, ENST00000933270, ENST00000962415, ENST00000962416

RefSeq mRNA: 1 — MANE Select: NM_015111 NM_015111

CCDS: CCDS34307

Canonical transcript exons

ENST00000274605 — 5 exons

Exon	Start	End
ENSE00000972974	178119554	178119913
ENSE00000972976	178121098	178121352
ENSE00001156142	178121474	178126081
ENSE00001194893	178120178	178120699
ENSE00001339581	178113532	178113771

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 85.15.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7036 / max 45.2245, expressed in 808 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60513	2.4587	695
60514	0.8893	385
60512	0.3556	194

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	85.15	gold quality
esophagus mucosa	UBERON:0002469	81.13	gold quality
endometrium epithelium	UBERON:0004811	78.85	silver quality
pancreatic ductal cell	CL:0002079	76.77	silver quality
skin of leg	UBERON:0001511	75.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.11	gold quality
skin of abdomen	UBERON:0001416	73.56	gold quality
esophagus	UBERON:0001043	72.92	gold quality
cortical plate	UBERON:0005343	72.55	gold quality
prefrontal cortex	UBERON:0000451	72.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.89	gold quality
zone of skin	UBERON:0000014	71.73	gold quality
right lung	UBERON:0002167	71.72	gold quality
cerebellar hemisphere	UBERON:0002245	71.66	gold quality
cerebellar cortex	UBERON:0002129	71.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.11	gold quality
right frontal lobe	UBERON:0002810	70.36	gold quality
cerebellum	UBERON:0002037	70.18	gold quality
apex of heart	UBERON:0002098	69.96	gold quality
gastrocnemius	UBERON:0001388	69.36	gold quality
muscle of leg	UBERON:0001383	69.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.98	gold quality
cervix squamous epithelium	UBERON:0006922	67.83	gold quality
upper lobe of left lung	UBERON:0008952	67.79	gold quality
periodontal ligament	UBERON:0008266	67.71	gold quality
frontal cortex	UBERON:0001870	67.67	gold quality
upper lobe of lung	UBERON:0008948	67.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.18	gold quality
neocortex	UBERON:0001950	66.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting N4BP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1825	99.72	68.11	1089

Literature-anchored findings (GeneRIF, showing 3)

• N4BP3 was associated with the survival time of cervical squamous cell carcinoma patients. mir-451 and mir-486 were related to tumor differentiation stage. (PMID:29343084)
• N4BP3 promotes angiogenesis in hepatocellular carcinoma by binding with KAT2B. (PMID:35848906)
• N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation. (PMID:36162713)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	n4bp3	ENSDARG00000060007
mus_musculus	N4bp3	ENSMUSG00000001053
rattus_norvegicus	N4bp3	ENSRNOG00000021731

Protein

Protein identifiers

NEDD4-binding protein 3 — O15049 (reviewed: O15049)

All UniProt accessions (1): O15049

UniProt curated annotations — full annotation on UniProt →

Function. Plays a positive role in the antiviral innate immune signaling pathway. Mechanistically, interacts with MAVS and functions as a positive regulator to promote ‘Lys-63’-linked polyubiquitination of MAVS and thus strengthens the interaction between MAVS and TRAF2. Also plays a role in axon and dendrite arborization during cranial nerve development. May also be important for neural crest migration and early development of other anterior structures including eye, brain and cranial cartilage.

Subunit / interactions. Binds NEDD4. Interacts with 14-3-3 proteins. Interacts with MAVS.

Subcellular location. Cytoplasmic vesicle. Cell projection. Axon. Dendrite.

Similarity. Belongs to the N4BP3 family.

RefSeq proteins (1): NP_055926* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033571	N4BP3	Family

Pfam: PF06818

UniProt features (11 total): region of interest 4, sequence conflict 3, chain 1, coiled-coil region 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15049-F1	65.88	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 176

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GGTGTGT_MIR329, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, BROWNE_HCMV_INFECTION_14HR_DN, TCCCCAC_MIR491, BROWNE_HCMV_INFECTION_24HR_DN, GOCC_NEURON_PROJECTION, SAGIV_CD24_TARGETS_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_SOMATODENDRITIC_COMPARTMENT, GOCC_AXON, MODULE_49, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, DUTERTRE_ESTRADIOL_RESPONSE_6HR_DN

GO Biological Process (3): nervous system development (GO:0007399), innate immune response (GO:0045087), immune system process (GO:0002376)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): axon (GO:0030424), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection	2
system development	1
immune response	1
defense response to symbiont	1
biological_process	1
binding	1
dendritic tree	1
cytoplasm	1
intracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
N4BP3	NEDD4	P46934	582
N4BP3	TSNAXIP1	Q2TAA8	451
N4BP3	FAM110D	Q8TAY7	406
N4BP3	SPEF1	Q9Y4P9	390
N4BP3	SCRT2	Q9NQ03	364
N4BP3	SEC14L3	Q9UDX4	356
N4BP3	RAB28	P51157	350
N4BP3	NHP2	Q9NX24	346
N4BP3	UNC119B	A6NIH7	325
N4BP3	GPRIN2	O60269	324
N4BP3	CARMIL3	Q8ND23	321
N4BP3	HIGD2A	Q9BW72	318
N4BP3	ZFP3	Q96NJ6	316
N4BP3	MAP7D3	Q8IWC1	315
N4BP3	MEGF11	A6BM72	314

IntAct

107 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
N4BP3	RNF41	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
Nedd4	N4BP3	psi-mi:“MI:0915”(physical association)	0.590
N4BP3	Nedd4	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
N4BP3	LMO4	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	CNKSR3	psi-mi:“MI:0915”(physical association)	0.560
CTDSP2	N4BP3	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	PRR35	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	SPG21	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	CCDC17	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	UBASH3A	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	CCDC146	psi-mi:“MI:0915”(physical association)	0.560
N4BP3	RFC5	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	N4BP3	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
N4BP3	BPNT2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (74): N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Affinity Capture-MS), N4BP3 (Two-hybrid), N4BP3 (Two-hybrid)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: A0A1L8GUX5, A0A1L8GXY6, A2AHG0, O15049, O60299, P60853, Q3LUD3, Q3LUD4, Q5U4W1, Q5ZLT3, Q6DIS8, Q8C7U1, Q8CFC9, Q8K1Q4, Q91YU6, Q9Y250, A5PKL7, Q9BRK4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	156.8×	1e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	138.3×	2e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	138.3×	2e-12
Activation of BH3-only proteins	7	102.2×	2e-11
RHO GTPases activate PKNs	7	65.3×	4e-10
Intrinsic Pathway for Apoptosis	7	60.3×	6e-10
FOXO-mediated transcription	5	49.4×	7e-07
SARS-CoV-1-host interactions	7	36.2×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	33.3×	8e-05
substantia nigra development	5	33.3×	8e-05
intracellular protein localization	7	13.3×	1e-04
endocytosis	6	10.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

143 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

987 predictions. Top by Δscore:

Variant	Effect	Δscore
5:178113770:TGG:T	donor_loss	1.0000
5:178113772:G:GG	donor_gain	1.0000
5:178113772:GT:G	donor_loss	1.0000
5:178120701:T:G	donor_loss	1.0000
5:178121335:G:GT	donor_gain	1.0000
5:178121338:G:GT	donor_gain	1.0000
5:178121348:GGGAG:G	donor_gain	1.0000
5:178121349:GGAGG:G	donor_gain	1.0000
5:178121350:G:GT	donor_gain	1.0000
5:178121350:GAGG:G	donor_loss	1.0000
5:178121351:AGGTG:A	donor_loss	1.0000
5:178121352:GGTG:G	donor_loss	1.0000
5:178121353:GTGA:G	donor_loss	1.0000
5:178121354:T:A	donor_loss	1.0000
5:178113767:CCATG:C	donor_gain	0.9900
5:178113768:CATG:C	donor_gain	0.9900
5:178113769:ATG:A	donor_gain	0.9900
5:178113770:TG:T	donor_gain	0.9900
5:178113771:GG:G	donor_gain	0.9900
5:178119901:T:TA	donor_gain	0.9900
5:178119911:AAGG:A	donor_loss	0.9900
5:178119914:GT:G	donor_loss	0.9900
5:178120172:T:A	acceptor_gain	0.9900
5:178120176:A:AG	acceptor_gain	0.9900
5:178120177:G:GG	acceptor_gain	0.9900
5:178120696:GCAG:G	donor_gain	0.9900
5:178121092:T:A	acceptor_gain	0.9900
5:178121093:GACAG:G	acceptor_loss	0.9900
5:178121095:CAGGT:C	acceptor_loss	0.9900
5:178121096:A:AC	acceptor_loss	0.9900

AlphaMissense

3487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:178121509:G:C	K381N	0.998
5:178121509:G:T	K381N	0.998
5:178121517:T:C	L384P	0.997
5:178121502:T:C	L379P	0.995
5:178121507:A:G	K381E	0.995
5:178121845:G:C	W493C	0.995
5:178121845:G:T	W493C	0.995
5:178121221:G:C	A326P	0.994
5:178121496:T:C	I377T	0.994
5:178121508:A:T	K381M	0.994
5:178121857:G:C	K497N	0.994
5:178121857:G:T	K497N	0.994
5:178121505:T:C	L380S	0.993
5:178121580:T:C	L405P	0.993
5:178121843:T:A	W493R	0.993
5:178121843:T:C	W493R	0.993
5:178121349:G:C	W368C	0.992
5:178121349:G:T	W368C	0.992
5:178121485:G:C	K373N	0.992
5:178121485:G:T	K373N	0.992
5:178121496:T:G	I377S	0.992
5:178121568:T:C	L401P	0.992
5:178121835:G:C	R490P	0.992
5:178121508:A:C	K381T	0.990
5:178121880:G:C	R505P	0.990
5:178119632:A:C	S17R	0.989
5:178119634:C:A	S17R	0.989
5:178119634:C:G	S17R	0.989
5:178121483:A:G	K373E	0.989
5:178121498:A:C	S378R	0.989

dbSNP variants (sampled 300 via entrez): RS1000208965 (5:178122421 T>C), RS1000385296 (5:178119930 G>A), RS1000445217 (5:178116898 C>T), RS1000448739 (5:178114260 C>T), RS1000543544 (5:178115866 A>C,G), RS1000556218 (5:178122348 A>T), RS1000808264 (5:178127378 C>A,T), RS1000882014 (5:178120058 T>C), RS1001208873 (5:178113393 C>T), RS1001352127 (5:178112941 CTG>C), RS1001434380 (5:178113214 C>G), RS1001446564 (5:178118232 T>G), RS1001486963 (5:178119054 T>C), RS1001594691 (5:178123168 T>C), RS1001725004 (5:178113098 G>A,C)

Disease associations

OMIM: gene MIM:619140 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012256_12	SAPHO syndrome	1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases reaction, decreases expression, affects cotreatment, increases expression, affects binding	3
Valproic Acid	affects cotreatment, decreases expression	3
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
aflatoxin B2	decreases methylation	1
homosalate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Phenobarbital	affects expression	1
Polystyrenes	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Thimerosal	decreases expression	1
Triclosan	decreases expression	1
Zearalenone	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.