NPW

Summary

NPW (neuropeptide W, HGNC:30509) is a protein-coding gene on chromosome 16p13.3, encoding Neuropeptide W (Q8N729). Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland.

The product of this gene is processed into 23- and 30-amino acid neuropeptides that bind and activate two G-protein coupled receptors in the central nervous system. The neuropeptides have been shown to enhance cortisol secretion from adrenal cells through the adenylate cyclase/protein kinase A signaling cascade. The preproprotein is translated using a non-AUG initiation codon that is inferred from analyses of the mouse ortholog.

Source: NCBI Gene 283869 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_001099456

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30509
Approved symbol	NPW
Name	neuropeptide W
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PPL8
Ensembl gene	ENSG00000183971
Ensembl biotype	protein_coding
OMIM	607997
Entrez	283869

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000566435, ENST00000567649

RefSeq mRNA: 1 — MANE Select: NM_001099456 NM_001099456

CCDS: CCDS42102

Canonical transcript exons

ENST00000566435 — 2 exons

Exon	Start	End
ENSE00002607916	2020533	2020755
ENSE00002628094	2019785	2020312

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 89.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6593 / max 951.0753, expressed in 1527 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152166	8.7116	902
152164	2.0271	923
152165	1.7311	481
152169	0.1227	55
152167	0.0515	20
152168	0.0152	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.10	gold quality
decidua	UBERON:0002450	83.59	gold quality
right lobe of liver	UBERON:0001114	82.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.62	gold quality
stromal cell of endometrium	CL:0002255	73.01	gold quality
liver	UBERON:0002107	71.85	gold quality
pituitary gland	UBERON:0000007	68.74	gold quality
adenohypophysis	UBERON:0002196	68.20	gold quality
lower esophagus mucosa	UBERON:0035834	66.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	63.97	gold quality
skin of abdomen	UBERON:0001416	63.83	gold quality
skin of leg	UBERON:0001511	63.81	gold quality
mucosa of transverse colon	UBERON:0004991	61.66	gold quality
ectocervix	UBERON:0012249	61.13	gold quality
zone of skin	UBERON:0000014	60.70	gold quality
right testis	UBERON:0004534	59.89	gold quality
body of stomach	UBERON:0001161	59.22	gold quality
spleen	UBERON:0002106	58.48	gold quality
endocervix	UBERON:0000458	58.20	gold quality
left testis	UBERON:0004533	58.11	gold quality
body of uterus	UBERON:0009853	57.77	gold quality
metanephros cortex	UBERON:0010533	56.71	gold quality
testis	UBERON:0000473	56.41	gold quality
stomach	UBERON:0000945	56.02	gold quality
right uterine tube	UBERON:0001302	55.83	gold quality
omental fat pad	UBERON:0010414	55.64	gold quality
peritoneum	UBERON:0002358	55.60	gold quality
right adrenal gland	UBERON:0001233	55.39	gold quality
body of pancreas	UBERON:0001150	55.36	gold quality
adipose tissue of abdominal region	UBERON:0007808	54.82	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	101.05
E-HCAD-6	yes	32.21
E-GEOD-125970	yes	5.82
E-ANND-3	yes	3.95
E-HCAD-31	yes	3.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

1 targeting NPW, 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-3937	87.69	61.61	103

Literature-anchored findings (GeneRIF, showing 6)

• determined that non-AUG translation initiation is used to express human prepro-NPW (PMID:12130646)
• a non-AUG translation initiation site is used to express mouse prepro-Npw (PMID:12719537)
• Intracerebroventricular administration of NPW23 and NPW30 to free-feeding rats suppressed dark phase and fasting-induced food intake. Possibly NPW functions as an endogenous catabolic signaling molecule in the brain. (PMID:12959997)
• This review of NPW suggests that study of effects of this peptide may reveal its role in regulating feeding and energy metabolism coupled to leptin levels in the brain. (PMID:22826747)
• these studies indicated an inconsistency between plasma and gastric NPW expression in response to nutrient ingestion, suggesting food induced gastric NPW expression may play a more important role locally (PMID:25270269)
• our data highlight that NPW modulates the CaV1.2 currents via G protein-coupled receptor 7, and the presence of it influences arterial tone. (PMID:26536090)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npb	ENSDARG00000078828
mus_musculus	Npw	ENSMUSG00000071230
rattus_norvegicus	Npw	ENSRNOG00000012390

Paralogs (1): NPB (ENSG00000183979)

Protein

Protein identifiers

Neuropeptide W — Q8N729 (reviewed: Q8N729)

Alternative names: Preproprotein L8

All UniProt accessions (3): Q8N729, H3BT17, H3BT42

UniProt curated annotations — full annotation on UniProt →

Function. Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to stress. NPW23 activates GPR7 and GPR8 more efficiently than NPW30.

Subcellular location. Secreted.

Tissue specificity. Detected in cerebrospinal fluid and urine (at protein level). Detected at high levels in the substantia nigra, fetal kidney and trachea; at lower levels in testis, uterus, ovary and placenta. Not detectable in many regions of the central nervous system. Also detected at high levels in lymphoblastic leukemia and colorectal adenocarcinoma.

Similarity. Belongs to the neuropeptide B/W family.

RefSeq proteins (1): NP_001092926* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013297	Neuropept_BW_pre	Family
IPR013299	Neuropept_W_pre	Family

Pfam: PF15180

UniProt features (8 total): peptide 2, signal peptide 1, propeptide 1, region of interest 1, compositionally biased region 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N729-F1	58.59	0.00

Functional residue map

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

Glycosylation sites (1): 133

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: 43 (showing top): GOBP_BEHAVIOR, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_FEEDING_BEHAVIOR, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, FOSTER_KDM1A_TARGETS_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_UP, KAT5_TARGET_GENES, SNIP1_TARGET_GENES, ZNF830_TARGET_GENES, ZSCAN30_TARGET_GENES, BLANCO_MELO_HUMAN_PARAINFLUENZA_VIRUS_3_INFECTION_A594_CELLS_DN

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

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPW	NPBWR1	P48145	999
NPW	NPBWR2	P48146	999
NPW	NPB	Q8NG41	994
NPW	NMS	Q5H8A3	464
NPW	WBP11	Q9Y2W2	462
NPW	RLN3	Q8WXF3	457
NPW	TAC4	Q86UU9	443
NPW	BHLHA15	Q7RTS1	425
NPW	PRLH	P81277	423
NPW	PMCH	P20382	423
NPW	FABP4	P15090	402
NPW	NPS	P0C0P6	399
NPW	CARTPT	Q16568	398
NPW	OXT	P01178	397
NPW	HCRT	O43612	395

IntAct

18 interactions, top by confidence:

A	B	Type	Score
SDF4	ACAD11	psi-mi:“MI:0914”(association)	0.640
PSG3	MGRN1	psi-mi:“MI:0914”(association)	0.530
HTR3E	ARL6IP5	psi-mi:“MI:0914”(association)	0.530
FAM149B1	NPW	psi-mi:“MI:0915”(physical association)	0.400
SMAP1	NPW	psi-mi:“MI:0915”(physical association)	0.400
POPDC1	CALM1	psi-mi:“MI:0914”(association)	0.350
CRLF1	MANBA	psi-mi:“MI:0914”(association)	0.350
P3H1	FCHO1	psi-mi:“MI:0914”(association)	0.350
MMP10	HS3ST1	psi-mi:“MI:0914”(association)	0.350
CORT	HS3ST1	psi-mi:“MI:0914”(association)	0.350
DKK3	HS3ST1	psi-mi:“MI:0914”(association)	0.350
PMCH	VGF	psi-mi:“MI:0914”(association)	0.350
ZNF562	MDM2	psi-mi:“MI:0914”(association)	0.350
CHRNB3	GAMT	psi-mi:“MI:0914”(association)	0.350
HOXD10	NPW	psi-mi:“MI:0914”(association)	0.350
ZNF317	NPW	psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	HLA-DQB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): NPW (Reconstituted Complex), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS), NPW (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1B0GVZ6, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A2Z4LIS9, A0A494C0N9, A0A494C0Y3, A5A752, A5PKC7, A6NDZ8, A6NE82, A6NEL2, A6NJ08, A6NJI1, A6QP24, A6QPM6, A8MTW9, A8MXV6, A8MYA2, B1ARW8, O35182, O43541, O75474, O75638, O89113, O94850, P0C7X2, P24097, P50617, P70339, Q02080, Q2KID8, Q2KIS6, Q3UN58, Q5JPB2, Q63003, Q6NZ36, Q6UYE1, Q6ZSJ8

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

77 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2020310:CAGG:C	donor_loss	0.9800
16:2020313:G:GA	donor_loss	0.9800
16:2020308:GCCAG:G	donor_gain	0.9500
16:2020313:G:GG	donor_gain	0.9200
16:2019638:TGCTC:T	donor_gain	0.9100
16:2019639:GCTCA:G	donor_gain	0.8800
16:2020532:GA:G	acceptor_gain	0.8700
16:2020531:A:AG	acceptor_gain	0.8400
16:2020532:G:GG	acceptor_gain	0.8400
16:2020311:AG:A	donor_gain	0.8100
16:2020312:GG:G	donor_gain	0.8100
16:2020640:T:TA	acceptor_gain	0.7500
16:2020310:CAG:C	donor_gain	0.7400
16:2020527:CGTTA:C	acceptor_loss	0.7400
16:2020528:GTTA:G	acceptor_loss	0.7400
16:2020530:TAGAG:T	acceptor_loss	0.7400
16:2020531:A:T	acceptor_loss	0.7400
16:2020532:G:GT	acceptor_loss	0.7400
16:2020527:C:A	acceptor_gain	0.7200
16:2019631:A:AG	donor_gain	0.7100
16:2019632:G:GG	donor_gain	0.7100
16:2020309:CCAG:C	donor_gain	0.7000
16:2020325:G:T	donor_gain	0.6600
16:2020532:GAGA:G	acceptor_gain	0.6600
16:2019640:CTCAA:C	donor_gain	0.6500
16:2020532:GAGAC:G	acceptor_gain	0.6400
16:2020532:G:C	acceptor_gain	0.5900
16:2020014:C:T	donor_gain	0.5700
16:2020310:CAGGT:C	donor_gain	0.5400
16:2020311:AGGT:A	donor_gain	0.5400

AlphaMissense

1004 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2020006:G:C	K35N	0.994
16:2020006:G:T	K35N	0.994
16:2020005:A:T	K35M	0.981
16:2020038:G:A	G46D	0.981
16:2020016:A:C	S39R	0.980
16:2020018:T:A	S39R	0.980
16:2020018:T:G	S39R	0.980
16:2020037:G:C	G46R	0.978
16:2020061:G:A	G54R	0.978
16:2020061:G:C	G54R	0.978
16:2020049:G:C	G50R	0.975
16:2020047:C:A	A49D	0.974
16:2020050:G:A	G50D	0.974
16:2020001:T:C	Y34H	0.972
16:2020038:G:T	G46V	0.972
16:2019998:T:A	W33R	0.969
16:2019998:T:C	W33R	0.969
16:2020037:G:T	G46C	0.969
16:2020056:T:A	L52H	0.968
16:2020000:G:C	W33C	0.966
16:2020000:G:T	W33C	0.966
16:2020004:A:G	K35E	0.966
16:2020040:C:A	R47S	0.964
16:2020053:T:C	L51P	0.964
16:2020044:C:A	A48D	0.962
16:2020061:G:T	G54W	0.960
16:2020032:C:A	T44K	0.957
16:2020005:A:C	K35T	0.948
16:2020002:A:G	Y34C	0.945
16:2020046:G:C	A49P	0.943

dbSNP variants (sampled 300 via entrez): RS1000082642 (16:2019718 C>A,T), RS1000722735 (16:2020935 G>A), RS1001039265 (16:2020730 C>T), RS1001708172 (16:2018488 C>T), RS1002247330 (16:2021171 C>G), RS1002302699 (16:2020802 C>A,T), RS1003152818 (16:2019343 A>G,T), RS1003162650 (16:2019530 C>A,T), RS1004808244 (16:2020421 C>A,T), RS1004859064 (16:2020625 TC>T,TCC), RS1004983972 (16:2019988 C>G,T), RS1005578518 (16:2021205 T>C,G), RS1008934030 (16:2018913 G>C), RS1009069910 (16:2020365 G>C,T), RS1009764765 (16:2020763 G>C,T)

Disease associations

OMIM: gene MIM:607997 | 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
GCST006585_1575	Blood protein levels	1.000000e-74

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression, increases expression	1
obeticholic acid	decreases expression	1
ICG 001	affects expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Genistein	increases expression	1
Particulate Matter	increases abundance, increases expression	1
Endocannabinoids	affects binding, decreases reaction, increases activity	1

Clinical trials (associated diseases)

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