NPIPB4

Summary

NPIPB4 (nuclear pore complex interacting protein family member B4, HGNC:41985) is a protein-coding gene on chromosome 16p12.2, encoding Nuclear pore complex-interacting protein family member B4 (C9JG80).

Predicted to be located in membrane.

Source: NCBI Gene 440345 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 3 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001384980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:41985
Approved symbol	NPIPB4
Name	nuclear pore complex interacting protein family member B4
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185864
Ensembl biotype	protein_coding
Entrez	440345

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 protein_coding_CDS_not_defined, 8 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000165086, ENST00000341400, ENST00000518761, ENST00000520808, ENST00000529969, ENST00000536041, ENST00000538859, ENST00000539191, ENST00000539318, ENST00000540103, ENST00000541329, ENST00000541674, ENST00000542133, ENST00000542338, ENST00000543449, ENST00000543654, ENST00000543660, ENST00000544693, ENST00000545367, ENST00000614197, ENST00000682606, ENST00000956755

RefSeq mRNA: 5 — MANE Select: NM_001384980 NM_001310148, NM_001384979, NM_001384980, NM_001384981, NM_001384982

CCDS: CCDS92123

Canonical transcript exons

ENST00000639157 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 99.26.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.26	gold quality
colonic epithelium	UBERON:0000397	99.07	gold quality
right testis	UBERON:0004534	99.01	gold quality
left testis	UBERON:0004533	98.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.91	gold quality
cerebellum	UBERON:0002037	98.70	gold quality
cerebellar cortex	UBERON:0002129	98.70	gold quality
cerebellar hemisphere	UBERON:0002245	98.69	gold quality
right uterine tube	UBERON:0001302	98.63	gold quality
bone marrow cell	CL:0002092	98.53	gold quality
right lobe of thyroid gland	UBERON:0001119	98.27	gold quality
mucosa of stomach	UBERON:0001199	98.25	gold quality
left lobe of thyroid gland	UBERON:0001120	98.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.17	gold quality
zone of skin	UBERON:0000014	98.15	gold quality
corpus callosum	UBERON:0002336	98.15	gold quality
skin of leg	UBERON:0001511	98.14	gold quality
thyroid gland	UBERON:0002046	98.13	gold quality
skin of abdomen	UBERON:0001416	98.11	gold quality
calcaneal tendon	UBERON:0003701	98.04	gold quality
uterine cervix	UBERON:0000002	98.00	gold quality
left ovary	UBERON:0002119	97.95	gold quality
endometrium	UBERON:0001295	97.92	gold quality
endocervix	UBERON:0000458	97.89	gold quality
right ovary	UBERON:0002118	97.89	gold quality
bone element	UBERON:0001474	97.85	gold quality
bone marrow	UBERON:0002371	97.85	gold quality
peripheral nervous system	UBERON:0000010	97.83	gold quality
nerve	UBERON:0001021	97.83	gold quality
tibial nerve	UBERON:0001323	97.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	230.64
E-ANND-3	yes	13.73
E-MTAB-9067	yes	12.86
E-GEOD-106540	no	75.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NPIPB4, 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-656-3P	100.00	72.15	2788
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-1288-3P	96.86	66.95	536
HSA-MIR-3169	96.40	67.58	698

Cross-species orthologs

0 orthologs

Paralogs (19): NPIPB12 (ENSG00000169203), NPIPB3 (ENSG00000169246), NPIPA1 (ENSG00000183426), NPIPA5 (ENSG00000183793), NPIPA6 (ENSG00000183889), NPIPB15 (ENSG00000196436), NPIPB9 (ENSG00000196993), NPIPB13 (ENSG00000198064), NPIPB6 (ENSG00000198156), NPIPA8 (ENSG00000214940), NPIPA7 (ENSG00000214967), NPIPA3 (ENSG00000224712), NPIPA9 (ENSG00000233024), NPIPB7 (ENSG00000233232), NPIPB2 (ENSG00000234719), NPIPB5 (ENSG00000243716), NPIPB11 (ENSG00000254206), NPIPA2 (ENSG00000254852), NPIPB8 (ENSG00000255524)

Protein

Protein identifiers

Nuclear pore complex-interacting protein family member B4 — C9JG80 (reviewed: C9JG80)

All UniProt accessions (9): A0A087WT63, A0A804HK81, C9JB18, E5RHP9, E7EQW1, F5GWQ4, F5H108, F5H5F2, F5H8A1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the NPIP family.

RefSeq proteins (5): NP_001297077, NP_001371908, NP_001371909, NP_001371910, NP_001371911 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009443	NPIP	Family
IPR048893	NPB13-like_MII_rpt	Repeat
IPR054697	NPIP_N	Domain

Pfam: PF06409, PF20885

UniProt features (15 total): compositionally biased region 10, region of interest 3, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9JG80-F1	40.69	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): chr16p12, CHICAS_RB1_TARGETS_LOW_SERUM, LU_EZH2_TARGETS_DN, JOHNSTONE_PARVB_TARGETS_1_DN, PECE_MAMMARY_STEM_CELL_DN, GHANDHI_DIRECT_IRRADIATION_UP, JAK2_DN.V1_DN, MIR6844, MIR3934_3P, DESCARTES_FETAL_CEREBELLUM_VASCULAR_ENDOTHELIAL_CELLS, DESCARTES_FETAL_CEREBRUM_VASCULAR_ENDOTHELIAL_CELLS, SS18_SSX1_FUSION_UNIPROT_Q8IZH1_UNREVIEWED_TARGET_GENES, HE_LIM_SUN_FETAL_LUNG_C1_GHRL_POS_NE_PRECURSOR_CELL, HE_LIM_SUN_FETAL_LUNG_C5_CD5_POS_CCL22_POS_MATURE_B_CELL

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

671 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPIPB4	SIAE	Q9HAT2	507
NPIPB4	DEPDC4	Q8N2C3	448
NPIPB4	KRTAP4-8	Q9BYQ9	447
NPIPB4	MTRNR2L3	P0CJ70	445
NPIPB4	KRTAP5-7	Q6L8G8	420
NPIPB4	NAB2	Q15742	390
NPIPB4	CCSER2	Q9H7U1	359
NPIPB4	NWD2	Q9ULI1	327
NPIPB4	CLEC17A	Q6ZS10	322
NPIPB4	PHYHD1	Q5SRE7	313
NPIPB4	ZBTB8OS	Q8IWT0	308
NPIPB4	GXYLT1	Q4G148	297
NPIPB4	NIBAN3	Q86XR2	293
NPIPB4	SGSM1	Q2NKQ1	292
NPIPB4	CDC42EP1	Q00587	290

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A023PXQ4, A0A0U1RQI7, A6NJU9, A6NNC1, A8MRT5, A8MUU9, C9JG80, E2RYF6, E5RHQ5, F8W0I5, O13534, O59779, P08399, P0C732, P0C785, P0DTH6, P0DW28, P13208, P15941, P21787, P24856, P39564, P51861, P87269, Q00130, Q01456, Q12444, Q13117, Q1HVI8, Q27905, Q2EEQ3, Q4ZJY7, Q4ZJZ0, Q5SDL7, Q63661, Q69577, Q6B0Y1, Q6RY98, Q6ZQT0, Q6ZRX8

Diamond homologs: A0A0B4J1W7, A6NHN6, A6NJ64, A6NJU9, A8MRT5, C9JG80, E5RHQ5, E9PIF3, E9PJ23, E9PJI5, E9PKD4, E9PQR5, F8W0I5, F8W1W9, F8WFD2, O75200, P0DM63, P0DXC3, Q92617, Q9UND3, O70490, Q08AH1, Q08AH3, Q3UNX5, Q53FZ2, Q5REV5, Q68CK6, Q6AYT9, Q6NUN0, Q6SKG1, Q8BGA8, Q8K0L3, Q91VA0, Q9BEA2, A0A179HJB8, A4YDT1, C0SPB0, P0C7M7, P39062, Q6P461

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1330175	GRCh37/hg19 16p12.2(chr16:21751992-22546976)x1	Pathogenic

SpliceAI

840 predictions. Top by Δscore:

Variant	Effect	Δscore
16:21839248:A:AC	donor_gain	1.0000
16:21839249:C:CC	donor_gain	1.0000
16:21843384:A:AC	donor_gain	1.0000
16:21843385:C:CC	donor_gain	1.0000
16:21843692:ACCTT:A	donor_gain	1.0000
16:21843693:CCTTC:C	donor_gain	1.0000
16:21843696:T:A	donor_gain	1.0000
16:21843791:CAC:C	acceptor_gain	1.0000
16:21847405:ATACT:A	donor_loss	1.0000
16:21847407:ACTC:A	donor_loss	1.0000
16:21847408:CTC:C	donor_loss	1.0000
16:21847409:TCA:T	donor_loss	1.0000
16:21847411:A:AC	donor_gain	1.0000
16:21847411:AC:A	donor_gain	1.0000
16:21847411:ACC:A	donor_gain	1.0000
16:21847411:ACCCA:A	donor_loss	1.0000
16:21847412:C:CC	donor_gain	1.0000
16:21847412:CC:C	donor_gain	1.0000
16:21847412:CCC:C	donor_gain	1.0000
16:21847412:CCCA:C	donor_gain	1.0000
16:21847412:CCCAA:C	donor_gain	1.0000
16:21847491:TCC:T	donor_gain	1.0000
16:21840434:T:TC	acceptor_gain	0.9900
16:21843581:CCT:C	acceptor_gain	0.9900
16:21843583:T:C	acceptor_gain	0.9900
16:21843688:CCATA:C	donor_loss	0.9900
16:21843689:CATA:C	donor_loss	0.9900
16:21843690:ATAC:A	donor_loss	0.9900
16:21843691:TA:T	donor_loss	0.9900
16:21843693:C:CG	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000390365 (16:21852030 G>A,C), RS1002901982 (16:21840534 C>A,T), RS1002954338 (16:21834457 A>G,T), RS1005188652 (16:21843123 A>T), RS1005652589 (16:21841990 G>A), RS1006252606 (16:21834293 C>A,T), RS1006612617 (16:21834414 C>T), RS1009178936 (16:21849433 C>A,G,T), RS1010157218 (16:21852080 T>C), RS1012008177 (16:21850655 G>C,T), RS1013005764 (16:21841248 C>T), RS1013134920 (16:21840706 T>C), RS1014403265 (16:21847391 T>C), RS1014940970 (16:21834438 C>G,T), RS1015407551 (16:21834294 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (2): intellectual disability (MONDO:0001071), obesity disorder (MONDO:0011122)

Orphanet (3): Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001513	Obesity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011741_44	LDL cholesterol levels in HIV infection	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	increases expression	1
manganese chloride	decreases expression, increases abundance	1
mono(2-ethyl-5-oxohexyl)phthalate	affects expression	1
ICG 001	affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Manganese	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity