N4BP2L1

Summary

N4BP2L1 (NEDD4 binding protein 2 like 1, HGNC:25037) is a protein-coding gene on chromosome 13q13.1, encoding NEDD4-binding protein 2-like 1 (Q5TBK1). Might play a role in adipocyte differentiation and triglyceride accumulation.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_052818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25037
Approved symbol	N4BP2L1
Name	NEDD4 binding protein 2 like 1
Location	13q13.1
Locus type	gene with protein product
Status	Approved
Aliases	CG018
Ensembl gene	ENSG00000139597
Ensembl biotype	protein_coding
OMIM	621053
Entrez	90634

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000343281, ENST00000380130, ENST00000380133, ENST00000380139, ENST00000459716, ENST00000464470, ENST00000472298, ENST00000495479, ENST00000530622, ENST00000613078, ENST00000635178, ENST00000635608, ENST00000970429, ENST00000970430

RefSeq mRNA: 15 — MANE Select: NM_052818 NM_001079691, NM_001286459, NM_001286460, NM_001286461, NM_001353627, NM_001353628, NM_001353629, NM_001353630, NM_001353631, NM_001353632, NM_001353633, NM_001353634, NM_001353635, NM_001353637, NM_052818

CCDS: CCDS41877, CCDS9345

Canonical transcript exons

ENST00000380130 — 5 exons

Exon	Start	End
ENSE00001767228	32400723	32403200
ENSE00003695690	32407250	32407338
ENSE00003696199	32407645	32407772
ENSE00003700157	32404321	32404397
ENSE00003890107	32427904	32428130

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2094 / max 305.7691, expressed in 1248 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136705	8.1472	946
136706	3.6687	1036
136708	0.2433	137
136707	0.1502	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.18	gold quality
monocyte	CL:0000576	95.27	gold quality
endothelial cell	CL:0000115	95.21	gold quality
mononuclear cell	CL:0000842	95.21	gold quality
left ovary	UBERON:0002119	95.04	gold quality
leukocyte	CL:0000738	94.93	gold quality
liver	UBERON:0002107	94.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.54	gold quality
skin of hip	UBERON:0001554	94.22	gold quality
cerebellar hemisphere	UBERON:0002245	94.19	gold quality
middle temporal gyrus	UBERON:0002771	94.18	gold quality
cerebellar cortex	UBERON:0002129	94.15	gold quality
upper leg skin	UBERON:0004262	94.14	gold quality
pituitary gland	UBERON:0000007	93.90	gold quality
adenohypophysis	UBERON:0002196	93.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.86	gold quality
primary visual cortex	UBERON:0002436	93.81	gold quality
germinal epithelium of ovary	UBERON:0001304	93.80	gold quality
cerebellum	UBERON:0002037	93.63	gold quality
right lung	UBERON:0002167	93.51	gold quality
right ovary	UBERON:0002118	93.41	gold quality
nucleus accumbens	UBERON:0001882	93.09	gold quality
mucosa of stomach	UBERON:0001199	92.97	gold quality
ovary	UBERON:0000992	92.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.87	gold quality
occipital lobe	UBERON:0002021	92.70	gold quality
right uterine tube	UBERON:0001302	92.57	gold quality
right frontal lobe	UBERON:0002810	92.49	gold quality
granulocyte	CL:0000094	92.22	gold quality
tibial artery	UBERON:0007610	91.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.06
E-CURD-88	yes	5.88
E-MTAB-7249	no	87.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting N4BP2L1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 2)

• Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (PMID:27184799)
• MicroRNA-150-5p-mediated Inhibition of Cell Proliferation, G1/S Transition, and Migration in Bladder Cancer through Targeting NEDD4-binding Protein 2-like 1 Gene. (PMID:38910572)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	N4bp2l1	ENSMUSG00000041132
rattus_norvegicus	N4bp2l1	ENSRNOG00000059322

Paralogs (2): N4BP2 (ENSG00000078177), N4BP2L2 (ENSG00000244754)

Protein

Protein identifiers

NEDD4-binding protein 2-like 1 — Q5TBK1 (reviewed: Q5TBK1)

All UniProt accessions (8): A0A0U1RQG8, A0A0U1RR05, A0A0U1RRA5, Q5TBK1, H0Y2Y5, Q9Y273, U3KPU5, U3KQ14

UniProt curated annotations — full annotation on UniProt →

Function. Might play a role in adipocyte differentiation and triglyceride accumulation.

Subunit / interactions. Interacts with dynactin subunit proteins, including DCTN4, DCTN5 and DCTN5.

Induction. Up-regulated by USF1. Up-regulated by FOXO1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TBK1-1	1	yes
Q5TBK1-2	2

RefSeq proteins (15): NP_001073159, NP_001273388, NP_001273389, NP_001273390, NP_001340556, NP_001340557, NP_001340558, NP_001340559, NP_001340560, NP_001340561, NP_001340562, NP_001340563, NP_001340564, NP_001340566, NP_438169* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026302	NEDD4-bd_p2	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF13671

UniProt features (3 total): chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TBK1-F1	78.29	0.62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, BASSO_B_LYMPHOCYTE_NETWORK, BROWNE_HCMV_INFECTION_8HR_UP, LOPEZ_MESOTHELIOMA_SURVIVAL_OVERALL_UP, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, BROWNE_HCMV_INFECTION_16HR_UP, chr13q13, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, WEI_MYCN_TARGETS_WITH_E_BOX, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BOYAULT_LIVER_CANCER_SUBCLASS_G23_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

667 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
N4BP2L1	CLVS1	Q8IUQ0	545
N4BP2L1	TMEM92	Q6UXU6	515
N4BP2L1	ZNF618	Q5T7W0	509
N4BP2L1	ANKS4B	Q8N8V4	507
N4BP2L1	PLA2G12B	Q9BX93	472
N4BP2L1	TRIM28	Q13263	447
N4BP2L1	ADAR	P55265	431
N4BP2L1	NT5DC3	Q86UY8	406
N4BP2L1	APOA2	P02652	394
N4BP2L1	ZNF589	Q86UQ0	392
N4BP2L1	GLIPR1L2	Q4G1C9	388
N4BP2L1	MCTS2	A0A3B3IRV3	383
N4BP2L1	AIMP2	Q13155	365
N4BP2L1	SPECC1	Q5M775	361
N4BP2L1	INTS4	Q96HW7	360

IntAct

3 interactions, top by confidence:

A	B	Type	Score
N4BP2L1	DCTN6	psi-mi:“MI:0914”(association)	0.350
N4BP2L1	DCTN3	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): DCTN5 (Affinity Capture-MS), DCTN3 (Affinity Capture-MS), ACTR10 (Affinity Capture-MS), PDLIM7 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS)

ESM2 similar proteins: A5HMM7, B3A0P5, B5LYJ9, C0HLU1, E1UYT9, E1UYU0, O75319, P19667, P30617, P37397, P53940, P85261, P86626, Q03380, Q04503, Q04740, Q08093, Q10R93, Q15417, Q2QYR1, Q2RBJ2, Q2VLK8, Q32L92, Q39487, Q3MK94, Q3SYU6, Q3V2Q8, Q43418, Q4FE47, Q4KM79, Q54CH1, Q5RFN6, Q5TBK1, Q5XHY7, Q6F495, Q6NXK5, Q7XI08, Q7XTS3, Q84JU4, Q8IEW1

Diamond homologs: P06623, P09543, P13233, P16330, Q5RFD0, Q5TBK1, Q29S05, Q3V2Q8, Q66H65, Q86UW6, Q8JZS6, Q92802, O64843, O74840, Q08954, Q9UTP4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1594 predictions. Top by Δscore:

Variant	Effect	Δscore
13:32403201:C:CC	acceptor_gain	1.0000
13:32403205:A:C	acceptor_gain	1.0000
13:32403196:TTCTT:T	acceptor_gain	0.9900
13:32403198:CTT:C	acceptor_gain	0.9900
13:32403199:TT:T	acceptor_gain	0.9900
13:32403205:A:AC	acceptor_gain	0.9900
13:32404416:A:C	acceptor_gain	0.9900
13:32406964:C:CT	acceptor_gain	0.9900
13:32407219:A:C	donor_gain	0.9900
13:32407241:T:TA	donor_gain	0.9900
13:32407646:T:TA	donor_gain	0.9900
13:32407671:T:TA	donor_gain	0.9900
13:32408512:CG:C	donor_gain	0.9900
13:32408517:A:AC	donor_gain	0.9900
13:32408518:T:C	donor_gain	0.9900
13:32427898:CATTA:C	donor_loss	0.9900
13:32427899:ATTAC:A	donor_loss	0.9900
13:32427900:TTACC:T	donor_loss	0.9900
13:32427901:TACC:T	donor_loss	0.9900
13:32427902:A:C	donor_loss	0.9900
13:32427903:C:A	donor_loss	0.9900
13:32403204:CA:C	acceptor_gain	0.9800
13:32404220:C:CT	donor_gain	0.9800
13:32407769:TTGT:T	acceptor_gain	0.9800
13:32408540:T:TA	donor_gain	0.9800
13:32408578:CTAT:C	donor_gain	0.9800
13:32406965:G:C	acceptor_gain	0.9700
13:32407773:C:CC	acceptor_gain	0.9700
13:32407780:G:C	acceptor_gain	0.9700
13:32407780:G:GC	acceptor_gain	0.9700

AlphaMissense

1633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:32404347:C:A	W149C	1.000
13:32404347:C:G	W149C	1.000
13:32404349:A:G	W149R	1.000
13:32404349:A:T	W149R	1.000
13:32407276:A:G	W124R	1.000
13:32407276:A:T	W124R	1.000
13:32407286:G:C	N120K	1.000
13:32407286:G:T	N120K	1.000
13:32407292:A:C	N118K	1.000
13:32407292:A:T	N118K	1.000
13:32407296:T:A	D117V	1.000
13:32407691:G:C	F87L	1.000
13:32407691:G:T	F87L	1.000
13:32407693:A:G	F87L	1.000
13:32427916:G:A	T56I	1.000
13:32427919:T:A	K55I	1.000
13:32427922:C:T	G54E	1.000
13:32427938:C:G	G49R	1.000
13:32403159:A:G	M172T	0.999
13:32403190:G:C	H162D	0.999
13:32403194:G:C	N160K	0.999
13:32403194:G:T	N160K	0.999
13:32404326:T:A	L156F	0.999
13:32404326:T:G	L156F	0.999
13:32404348:C:G	W149S	0.999
13:32404360:G:T	P145H	0.999
13:32404369:A:G	F142S	0.999
13:32407269:A:C	M126R	0.999
13:32407274:C:A	W124C	0.999
13:32407274:C:G	W124C	0.999

dbSNP variants (sampled 300 via entrez): RS1000018110 (13:32427761 C>A), RS1000239538 (13:32418583 C>G), RS1000395110 (13:32424609 C>A,T), RS1000526154 (13:32420151 T>A), RS1000578447 (13:32419803 A>G), RS1000595650 (13:32426432 C>A,T), RS1000846376 (13:32407527 G>C), RS1000864294 (13:32421748 T>C), RS1000948905 (13:32406899 C>A,T), RS1001009122 (13:32414405 G>A,C), RS1001133943 (13:32426079 G>A,C,T), RS1001192997 (13:32417202 T>G), RS1001240508 (13:32416961 C>T), RS1001263875 (13:32423639 G>A), RS1001276218 (13:32400419 A>T)

Disease associations

OMIM: gene MIM:621053 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001930_11	Breast cancer	6.000000e-06
GCST001937_19	Breast cancer	5.000000e-08
GCST006614_12	Total cholesterol levels	1.000000e-09
GCST008078_112	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-12
GCST008078_31	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-09
GCST008079_156	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-14
GCST008079_56	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-11
GCST008086_7	LDL cholesterol levels in current drinkers	3.000000e-06
GCST008367_8	Plasma anti-thyroglobulin and anti-thyroid peroxidase levels (bivariate analysis)	7.000000e-07
GCST009264_14	Thalamus volume	8.000000e-06
GCST010204_104	Low density lipoprotein cholesterol levels	8.000000e-27

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0006935	thalamus volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
entinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Formaldehyde	increases expression	2
Nickel	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
avobenzone	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Decitabine	affects expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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