NPBWR2

Summary

NPBWR2 (neuropeptides B and W receptor 2, HGNC:4530) is a protein-coding gene on chromosome 20q13.33, encoding Neuropeptides B/W receptor type 2 (P48146). Interacts specifically with a number of opioid ligands.

The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor. The encoded protein is similar in sequence to another G protein-coupled receptor (GPR7), and it is structurally similar to opioid and somatostatin receptors. This protein binds neuropeptides B and W. This gene is intronless and is expressed primarily in the frontal cortex of the brain.

Source: NCBI Gene 2832 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 63 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_005286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4530
Approved symbol	NPBWR2
Name	neuropeptides B and W receptor 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125522
Ensembl biotype	protein_coding
OMIM	600731
Entrez	2832

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000369768, ENST00000684052

RefSeq mRNA: 1 — MANE Select: NM_005286 NM_005286

CCDS: CCDS13557

Canonical transcript exons

ENST00000612646 — 0 exons

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 58.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1192 / max 16.8467, expressed in 41 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188464	0.0678	35
188463	0.0514	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	58.97	gold quality
superior frontal gyrus	UBERON:0002661	55.51	gold quality
prefrontal cortex	UBERON:0000451	53.02	gold quality
frontal cortex	UBERON:0001870	47.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	46.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	44.47	gold quality
bone marrow cell	CL:0002092	42.80	gold quality
cerebral cortex	UBERON:0000956	41.45	gold quality
right frontal lobe	UBERON:0002810	37.94	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
sural nerve	UBERON:0015488	36.72	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow	UBERON:0002371	36.32	gold quality
granulocyte	CL:0000094	36.09	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
pituitary gland	UBERON:0000007	34.60	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
adenohypophysis	UBERON:0002196	33.23	silver quality
brain	UBERON:0000955	32.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
tonsil	UBERON:0002372	31.98	gold quality
anterior cingulate cortex	UBERON:0009835	31.77	gold quality
leukocyte	CL:0000738	31.64	gold quality
blood	UBERON:0000178	31.06	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
monocyte	CL:0000576	30.24	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
urinary bladder	UBERON:0001255	29.78	gold quality
vermiform appendix	UBERON:0001154	29.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• distribution in central nervous system and peripheral tissues with precursor peptides (PMID:12401809)
• characterization of a family of endogenous neuropeptide ligands for this G protein-coupled receptor (PMID:12719537)
• Expressed in the zona glomerulosa and zona fasciculata-reticularis ( cells of the human adrenal cortex. (PMID:15797961)
• mainly expressed in brain or pituitary (PMID:27399877)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npbwr2a	ENSDARG00000079423
drosophila_melanogaster	Rh7	FBGN0036260
caenorhabditis_elegans	trhr-1	WBGENE00016265

Paralogs (17): OPRK1 (ENSG00000082556), OPRM1 (ENSG00000112038), KISS1R (ENSG00000116014), OPRD1 (ENSG00000116329), OPRL1 (ENSG00000125510), SSTR4 (ENSG00000132671), SSTR1 (ENSG00000139874), SSTR5 (ENSG00000162009), GPR149 (ENSG00000174948), SSTR2 (ENSG00000180616), UTS2R (ENSG00000181408), PTGDR2 (ENSG00000183134), CMKLR2 (ENSG00000183671), LTB4R (ENSG00000213903), LTB4R2 (ENSG00000213906), SSTR3 (ENSG00000278195), NPBWR1 (ENSG00000288611)

Protein

Protein identifiers

Neuropeptides B/W receptor type 2 — P48146 (reviewed: P48146)

Alternative names: G-protein coupled receptor 8

All UniProt accessions (1): P48146

UniProt curated annotations — full annotation on UniProt →

Function. Interacts specifically with a number of opioid ligands. Receptor for neuropeptides B and W, which may be involved in neuroendocrine system regulation, food intake and the organization of other signals.

Subcellular location. Cell membrane.

Tissue specificity. Detected at high levels in caudate nucleus, hippocampus and amygdala; at moderate levels in the adult brain, thalamus, parietal cortex, pituitary gland, adrenal gland and lymph nodes.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_005277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR009150	Neuropept_B/W_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (23 total): topological domain 8, transmembrane region 7, glycosylation site 3, sequence variant 2, chain 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48146-F1	83.39	0.53

Functional residue map

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

Disulfide bonds (1): 117–197

Glycosylation sites (3): 24, 29, 34

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: 34 (showing top): REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOCC_NEURON_PROJECTION, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_G_PROTEIN_COUPLED_OPIOID_RECEPTOR_SIGNALING_PATHWAY, GOMF_G_PROTEIN_COUPLED_OPIOID_RECEPTOR_ACTIVITY, KRAS.AMP.LUNG_UP.V1_UP, KRAS.PROSTATE_UP.V1_DN, GSE13411_NAIVE_BCELL_VS_PLASMA_CELL_DN, GSE13411_IGM_VS_SWITCHED_MEMORY_BCELL_UP

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), signal transduction (GO:0007165), G protein-coupled opioid receptor signaling pathway (GO:0038003)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), G protein-coupled opioid receptor activity (GO:0004985), neuropeptide receptor activity (GO:0008188), neuropeptide binding (GO:0042923), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), neuron projection (GO:0043005)

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 signaling pathway	3
G protein-coupled receptor activity	2
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled opioid receptor signaling pathway	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
peptide binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPBWR2	NPW	Q8N729	999
NPBWR2	NPB	Q8NG41	998
NPBWR2	INSL3	P51460	652
NPBWR2	RXFP2	Q8WXD0	524
NPBWR2	RPRM	Q9NS64	458
NPBWR2	TAL2	Q16559	418
NPBWR2	PMIS2	A0A1W2PS18	391
NPBWR2	OR51M1	Q9H341	371
NPBWR2	OR51I2	Q9H344	370
NPBWR2	GPR3	P46089	348
NPBWR2	ABHD16B	Q9H3Z7	336
NPBWR2	OR8D2	Q9GZM6	329
NPBWR2	OR2A14	Q96R47	324
NPBWR2	LRCH2	Q5VUJ6	321
NPBWR2	RXFP1	Q9HBX9	317

IntAct

59 interactions, top by confidence:

A	B	Type	Score
KRT31	NPBWR2	psi-mi:“MI:0915”(physical association)	0.720
NPBWR2	KRT31	psi-mi:“MI:0915”(physical association)	0.720
	NPBWR2	psi-mi:“MI:0915”(physical association)	0.560
NPBWR2	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	NPBWR2	psi-mi:“MI:0915”(physical association)	0.560
NPBWR2	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	NPBWR2	psi-mi:“MI:0915”(physical association)	0.560
KRT40	NPBWR2	psi-mi:“MI:0915”(physical association)	0.560
NPBWR2	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
NPBWR2	BOLL	psi-mi:“MI:0915”(physical association)	0.560
NPBWR2	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
NPBWR2		psi-mi:“MI:0915”(physical association)	0.560
NPBWR2	KRT40	psi-mi:“MI:0915”(physical association)	0.560
BOLL	NPBWR2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (18): KRTAP5-9 (Two-hybrid), KRT31 (Two-hybrid), PSMA3 (Two-hybrid), PNMA1 (Two-hybrid), BOLL (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), NPBWR2 (Two-hybrid), NPBWR2 (Two-hybrid), KRT34 (Two-hybrid), KRTAP6-2 (Two-hybrid), CYSRT1 (Two-hybrid)

ESM2 similar proteins: A0T2N3, F7EQ49, O08878, O70526, O88410, O88855, P30411, P46093, P46663, P48146, P49220, P49681, P49682, P49684, P50132, P51680, P51686, P56484, P79960, P97583, Q15722, Q1JQB3, Q1WLP9, Q28642, Q2TAD5, Q3BCU0, Q3T181, Q4KLH9, Q4VA82, Q56UD9, Q5KSK8, Q5MD61, Q61125, Q7SZP9, Q867B2, Q8BMP4, Q8BUD0, Q8HZN9, Q8HZP1, Q8HZP2

Diamond homologs: A5PLE7, B0UXR0, B5X337, D4A7K7, F1MV99, O08858, O35210, O35811, O77590, O88634, P11613, P21556, P25025, P25095, P25104, P25106, P26824, P29089, P29754, P29755, P30555, P30556, P30937, P30938, P31391, P32249, P32250, P32300, P33396, P33535, P34976, P35346, P35366, P35372, P35373, P35383, P41143, P41231, P41232, P42866

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Keratinization	8	31.8×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
150212	GRCh38/hg38 20q13.33(chr20:61326549-64277326)x3	Pathogenic

SpliceAI

131 predictions. Top by Δscore:

Variant	Effect	Δscore
20:64107080:T:TA	donor_gain	0.9900
20:64107067:T:TA	donor_gain	0.8100
20:64106076:G:A	donor_gain	0.6900
20:64106080:AGAG:A	donor_gain	0.6400
20:64106396:C:CT	donor_gain	0.6400
20:64106063:T:A	donor_gain	0.6300
20:64106247:TGGG:T	donor_gain	0.6300
20:64107081:C:A	donor_gain	0.5800
20:64107070:T:TA	donor_gain	0.5700
20:64107071:C:CA	donor_gain	0.5700
20:64106397:C:CT	donor_gain	0.5600
20:64107141:T:TA	donor_gain	0.5500
20:64107093:T:TA	donor_gain	0.5300
20:64106116:AG:A	donor_gain	0.5000
20:64107110:T:TA	donor_gain	0.5000
20:64106204:TGA:T	donor_gain	0.4900
20:64106279:C:CT	acceptor_gain	0.4600
20:64106277:A:T	acceptor_gain	0.4500
20:64106379:C:CA	donor_gain	0.4400
20:64106337:G:GT	donor_gain	0.4000
20:64106383:A:AC	donor_gain	0.4000
20:64106384:C:CC	donor_gain	0.4000
20:64106054:CGG:C	donor_gain	0.3900
20:64106420:T:C	donor_gain	0.3900
20:64107074:G:A	donor_gain	0.3900
20:64105917:G:C	donor_gain	0.3800
20:64106377:G:GT	donor_gain	0.3800
20:64106056:G:GC	donor_gain	0.3700
20:64106211:G:T	donor_gain	0.3700
20:64107132:TGGC:T	donor_gain	0.3700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000176602 (20:64109386 C>G,T), RS1001215708 (20:64107927 G>C), RS1001570379 (20:64107617 G>A,C,T), RS1001997917 (20:64107366 G>A), RS1002054180 (20:64107312 C>T), RS1003567225 (20:64105217 C>T), RS1003944240 (20:64105496 G>A), RS1004291856 (20:64108582 A>C,G), RS1005026410 (20:64104998 G>A), RS1005219764 (20:64107528 G>A), RS1005278526 (20:64108706 T>C), RS1005513510 (20:64104327 G>C), RS1005703341 (20:64107214 C>A,G,T), RS1007088882 (20:64106899 T>C), RS1009102910 (20:64104494 C>A,T)

Disease associations

OMIM: gene MIM:600731 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002783_321	Body mass index	8.000000e-06
GCST007001_16	Cerebrospinal AB1-42 levels in normal cognition	3.000000e-07
GCST007930_1	Medication use (agents acting on the renin-angiotensin system)	4.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523864 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Neuropeptide W/neuropeptide B receptors

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
neuropeptide W-23	Full agonist	9.6	pIC50
neuropeptide W-30	Full agonist	9.4	pIC50
neuropeptide B-29	Full agonist	9.0	pIC50
neuropeptide B-23	Full agonist	8.4	pIC50
[125I]NPW-23 (human)	Agonist	7.7	pKd

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Carmustine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883545	Binding	PRESTO-Tango GPCRome screening (NPBW2)	Data for DCP probe UCSF924

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_KV56	cAMP Hunter CHO-K1 NPBWR2 Gi	Spontaneously immortalized cell line	Female
CVCL_KY61	PathHunter CHO-K1 NPBWR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZK29	Tango GPR8-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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