NPB

Summary

NPB (neuropeptide B, HGNC:30099) is a protein-coding gene on chromosome 17q25.3, encoding Neuropeptide B (Q8NG41). May be involved in the regulation of feeding, neuroendocrine system, memory, learning and in the afferent pain pathway. It is a selective cancer dependency (DepMap: 18.0% of cell lines).

This gene encodes a member of the neuropeptide B/W family of proteins and preproprotein that is proteolytically processed to generate multiple protein products. The encoded products include neuropeptide B-23 and a C-terminally extended form, neuropeptide B-29, which are characterized by an N-terminal brominated tryptophan amino acid. Both of the encoded peptides bind with higher affinity to neuropeptide B/W (NPB/W) receptor 1 compared to the related NPB/W receptor 2. These peptides may regulate feeding, pain perception, and stress in rodents.

Source: NCBI Gene 256933 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 11 total
• Cancer dependency (DepMap): dependent in 18.0% of screened cell lines
• MANE Select transcript: NM_148896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30099
Approved symbol	NPB
Name	neuropeptide B
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	PPL7, PPNPB
Ensembl gene	ENSG00000183979
Ensembl biotype	protein_coding
OMIM	607996
Entrez	256933

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000333383, ENST00000573081

RefSeq mRNA: 1 — MANE Select: NM_148896 NM_148896

CCDS: CCDS11790

Canonical transcript exons

ENST00000333383 — 2 exons

Exon	Start	End
ENSE00001627020	81902238	81902526
ENSE00001796527	81902620	81902905

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 78.51.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9868 / max 54.1666, expressed in 514 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163378	0.5305	280
163379	0.4563	214

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	78.51	gold quality
spinal cord	UBERON:0002240	76.58	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.19	gold quality
hypothalamus	UBERON:0001898	71.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	71.34	gold quality
vastus lateralis	UBERON:0001379	69.57	gold quality
quadriceps femoris	UBERON:0001377	69.48	gold quality
biceps brachii	UBERON:0001507	69.17	gold quality
substantia nigra	UBERON:0002038	67.77	gold quality
epithelium of nasopharynx	UBERON:0001951	66.87	gold quality
nucleus accumbens	UBERON:0001882	66.85	gold quality
midbrain	UBERON:0001891	66.68	gold quality
amygdala	UBERON:0001876	65.43	gold quality
stromal cell of endometrium	CL:0002255	64.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.13	gold quality
germinal epithelium of ovary	UBERON:0001304	64.12	gold quality
putamen	UBERON:0001874	63.35	gold quality
anterior cingulate cortex	UBERON:0009835	62.99	gold quality
temporal lobe	UBERON:0001871	62.97	gold quality
ventricular zone	UBERON:0003053	62.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.07	gold quality
ganglionic eminence	UBERON:0004023	61.16	gold quality
caudate nucleus	UBERON:0001873	60.83	gold quality
gingival epithelium	UBERON:0001949	60.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.33	gold quality
decidua	UBERON:0002450	60.23	gold quality
cerebellum	UBERON:0002037	59.66	gold quality
cerebellar cortex	UBERON:0002129	59.52	gold quality
gingiva	UBERON:0001828	59.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting NPB, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7846-3P	96.92	65.18	51
HSA-MIR-1282	91.07	71.26	99

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• identified a neuropeptide modified with bromine; an endogenous ligand for GPR7 (PMID:12118011)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npb	ENSDARG00000078828
mus_musculus	Npb	ENSMUSG00000044034
rattus_norvegicus	Npb	ENSRNOG00000076694

Paralogs (1): NPW (ENSG00000183971)

Protein

Protein identifiers

Neuropeptide B — Q8NG41 (reviewed: Q8NG41)

Alternative names: Preproprotein L7

All UniProt accessions (2): Q8NG41, I3NI19

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of feeding, neuroendocrine system, memory, learning and in the afferent pain pathway.

Subcellular location. Secreted.

Tissue specificity. Widely expressed in the central nervous system. High levels are found in substantia nigra, hypothalamus, hippocampus, spinal cord, placenta and fetal brain; lower levels are found in testis, uterus and ovary. Also detected at high levels in colorectal adenocarcinoma.

Similarity. Belongs to the neuropeptide B/W family.

RefSeq proteins (1): NP_683694* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013297	Neuropept_BW_pre	Family
IPR013298	Neuropept_B_pre	Family

Pfam: PF15180

UniProt features (5 total): peptide 2, signal peptide 1, propeptide 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NG41-F1	69.59	0.26

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 46 (showing top): GOBP_BEHAVIOR, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOMF_SIGNALING_RECEPTOR_BINDING, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_FEEDING_BEHAVIOR, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, CAMPS_COLON_CANCER_COPY_NUMBER_UP, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, SNRNP70_TARGET_GENES

GO Biological Process (3): G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), feeding behavior (GO:0007631)

GO Molecular Function (2): G protein-coupled receptor binding (GO:0001664), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
behavior	1
signaling receptor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPB	NPBWR1	P48145	999
NPB	NPBWR2	P48146	998
NPB	NPW	Q8N729	994
NPB	APLN	Q9ULZ1	575
NPB	NMS	Q5H8A3	545
NPB	GAL	P22466	522
NPB	PRLH	P81277	512
NPB	NPS	P0C0P6	489
NPB	GRP	P07491	483
NPB	NMB	P08949	475
NPB	GHRL	Q9UBU3	465
NPB	ALB	P02768	453
NPB	RLN3	Q8WXF3	432
NPB	NMU	P48645	424
NPB	KISS1R	Q969F8	423

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NPB	CST4	psi-mi:“MI:0914”(association)	0.530
NPB	IL16	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): PDP2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), MUC7 (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), CST2 (Affinity Capture-MS), PIGR (Affinity Capture-MS), IL16 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), UBR1 (Affinity Capture-MS), FKBP4 (Affinity Capture-MS), ADSS (Affinity Capture-MS), CST4 (Affinity Capture-MS), PROC (Affinity Capture-MS), MCCC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA5, A0A494C0Y3, A0JNN8, A2A9F4, A2ARS0, A2VDX9, A5A769, A5PJP1, A8MTW9, C9JTQ0, O54887, P0C171, P0DJK0, P0DPE3, P36343, P60531, P98162, Q13487, Q1HCM0, Q1LZC5, Q2TBK3, Q2VPJ9, Q566C8, Q5BLP8, Q5JTB6, Q5NRQ0, Q64322, Q68FX5, Q6F5E0, Q6QNY0, Q6VUP9, Q7TN12, Q7TPD7, Q867D0, Q8K025, Q8MJW9, Q8NAX2, Q8NG41, Q8TAP8, Q8TEF2

Diamond homologs: Q8K1M5, Q8K4P1, Q8MI35, Q8MJV4, Q8N729, Q8NG41, Q8K4P2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

129 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81902522:GCCTC:G	donor_gain	1.0000
17:81902514:GC:G	donor_gain	0.9900
17:81902527:G:GG	donor_gain	0.9900
17:81902525:TC:T	donor_gain	0.9800
17:81902351:G:GA	donor_gain	0.9700
17:81902619:GGCT:G	acceptor_gain	0.9700
17:81902523:CCTC:C	donor_gain	0.9600
17:81902524:CTC:C	donor_gain	0.9600
17:81902526:CG:C	donor_loss	0.9600
17:81902527:G:A	donor_loss	0.9600
17:81902528:T:A	donor_loss	0.9600
17:81902529:GAGT:G	donor_loss	0.9600
17:81902531:G:C	donor_loss	0.9600
17:81901211:A:T	acceptor_gain	0.9500
17:81902530:A:AC	donor_loss	0.9500
17:81902353:TAC:T	donor_gain	0.9200
17:81902354:ACA:A	donor_gain	0.9200
17:81902616:CCAG:C	acceptor_loss	0.9200
17:81902618:A:AG	acceptor_gain	0.9200
17:81902619:G:A	acceptor_loss	0.9200
17:81902619:G:GG	acceptor_gain	0.9200
17:81901214:A:C	acceptor_gain	0.9100
17:81901213:C:CT	acceptor_gain	0.8900
17:81902531:G:GG	donor_gain	0.8800
17:81901210:CAGCA:C	acceptor_gain	0.8600
17:81902530:A:AG	donor_gain	0.8600
17:81902532:TCCG:T	donor_gain	0.8400
17:81902618:AG:A	acceptor_gain	0.8400
17:81902619:GG:G	acceptor_gain	0.8400
17:81902616:CCAGG:C	acceptor_gain	0.8300

AlphaMissense

764 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81902695:T:A	C109S	0.957
17:81902696:G:C	C109S	0.957
17:81902358:G:C	K27N	0.925
17:81902358:G:T	K27N	0.925
17:81902696:G:A	C109Y	0.896
17:81902659:T:A	C97S	0.888
17:81902660:G:C	C97S	0.888
17:81902695:T:C	C109R	0.887
17:81902352:G:C	W25C	0.884
17:81902352:G:T	W25C	0.884
17:81902708:T:A	V113D	0.870
17:81902630:T:A	V87D	0.868
17:81902660:G:A	C97Y	0.868
17:81902696:G:T	C109F	0.860
17:81902390:G:A	G38D	0.858
17:81902697:C:G	C109W	0.855
17:81902350:T:A	W25R	0.854
17:81902350:T:C	W25R	0.854
17:81902710:T:C	F114L	0.854
17:81902712:C:A	F114L	0.854
17:81902712:C:G	F114L	0.854
17:81902659:T:C	C97R	0.848
17:81902627:G:A	C86Y	0.844
17:81902626:T:A	C86S	0.830
17:81902627:G:C	C86S	0.830
17:81902711:T:G	F114C	0.821
17:81902357:A:T	K27M	0.811
17:81902389:G:C	G38R	0.809
17:81902628:C:G	C86W	0.809
17:81902389:G:T	G38C	0.806

dbSNP variants (sampled 300 via entrez): RS1000430804 (17:81902767 A>G), RS1000839613 (17:81901539 T>C), RS1001118847 (17:81901763 C>T), RS1002197257 (17:81902296 C>T), RS1002247141 (17:81901878 CTG>C), RS1002248157 (17:81902112 C>A,G,T), RS1003187082 (17:81903371 G>C), RS1004255018 (17:81902493 G>A), RS1004526145 (17:81901130 C>A), RS1005381262 (17:81903197 T>A,C), RS1005439820 (17:81901199 C>T), RS1006977650 (17:81902232 T>C), RS1007204540 (17:81902524 C>G,T), RS1007486033 (17:81902711 T>C,G), RS1008037363 (17:81900237 T>C)

Disease associations

OMIM: gene MIM:607996 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
prothioconazole	decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression, decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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