NPVF

Summary

NPVF (neuropeptide VF precursor, HGNC:13782) is a protein-coding gene on chromosome 7p15.3, encoding Pro-FMRFamide-related neuropeptide VF (Q9HCQ7). Efficiently inhibits forskolin-induced production of cAMP.

Enables neuropeptide activity. Involved in negative regulation of gonadotropin secretion and neuropeptide signaling pathway. Is active in extracellular space.

Source: NCBI Gene 64111 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_022150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13782
Approved symbol	NPVF
Name	neuropeptide VF precursor
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	RFRP
Ensembl gene	ENSG00000105954
Ensembl biotype	protein_coding
OMIM	616984
Entrez	64111

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000222674

RefSeq mRNA: 1 — MANE Select: NM_022150 NM_022150

CCDS: CCDS5395

Canonical transcript exons

ENST00000222674 — 3 exons

Exon	Start	End
ENSE00000674096	25226626	25227026
ENSE00001206993	25224570	25225173
ENSE00001207002	25228302	25228486

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 53.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0406 / max 39.3495, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83162	0.0406	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	53.59	gold quality
hypothalamus	UBERON:0001898	50.50	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
renal glomerulus	UBERON:0000074	46.86	gold quality
metanephric glomerulus	UBERON:0004736	46.77	gold quality
nephron tubule	UBERON:0001231	46.71	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
nasal cavity epithelium	UBERON:0005384	44.87	gold quality
retina	UBERON:0000966	43.83	silver quality
pigmented layer of retina	UBERON:0001782	43.82	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
thymus	UBERON:0002370	43.21	gold quality
quadriceps femoris	UBERON:0001377	42.72	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
medulla oblongata	UBERON:0001896	41.74	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	24.44
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting NPVF, 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-7110-3P	100.00	73.18	2486
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255

Literature-anchored findings (GeneRIF, showing 3)

• GnIH homologs in the human hypothalamus and were identified and human GnIH receptor (GPR147) mRNA expression in the hypothalamus as well as in the pituitary, was characterized. (PMID:20027225)
• RFRP-3/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out (PMID:25180599)
• The distribution of Neuropeptide FF and Neuropeptide VF in central and peripheral tissues and their role in energy homeostasis control. (PMID:34534716)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npvf	ENSDARG00000036227
mus_musculus	Npvf	ENSMUSG00000029831
rattus_norvegicus	Npvf	ENSRNOG00000010806

Protein

Protein identifiers

Pro-FMRFamide-related neuropeptide VF — Q9HCQ7 (reviewed: Q9HCQ7)

All UniProt accessions (1): Q9HCQ7

UniProt curated annotations — full annotation on UniProt →

Function. Efficiently inhibits forskolin-induced production of cAMP. Acts as a potent negative regulator of gonadotropin synthesis and secretion. Induces secretion of prolactin. Efficiently inhibits forskolin-induced production of cAMP. Blocks morphine-induced analgesia. Shows no inhibitory activity of forskolin-induced production of cAMP.

Subcellular location. Secreted.

Tissue specificity. Specifically expressed in the retina. Detected in the hypothalamus. Detected in the hypothalamus.

Similarity. Belongs to the FARP (FMRFamide related peptide) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HCQ7-1	1	yes
Q9HCQ7-2	2

RefSeq proteins (1): NP_071433* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026297	FMRFamide-related/fGRP	Family

UniProt features (15 total): propeptide 4, peptide 4, sequence variant 3, modified residue 2, signal peptide 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCQ7-F1	58.43	0.03

Functional residue map

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

Post-translational modifications (2): 131, 92

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): YAATNRNNNYNATT_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, LHX3_01, FOXO1_01, CHX10_01, GOBP_CELL_CELL_SIGNALING, NKX62_Q2, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_ENDOCRINE_PROCESS, TGCTGAY_UNKNOWN, OCT1_03, GOBP_NEGATIVE_REGULATION_OF_SECRETION

GO Biological Process (2): neuropeptide signaling pathway (GO:0007218), negative regulation of gonadotropin secretion (GO:0032277)

GO Molecular Function (3): signaling receptor binding (GO:0005102), neuropeptide activity (GO:0160041), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
gonadotropin secretion	1
regulation of gonadotropin secretion	1
negative regulation of hormone secretion	1
negative regulation of multicellular organismal process	1
protein binding	1
receptor ligand activity	1
neuropeptide receptor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2227 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPVF	NPFFR1	Q9GZQ6	982
NPVF	NPFFR2	Q9Y5X5	907
NPVF	KISS1R	Q969F8	864
NPVF	KISS1	Q15726	847
NPVF	NPFF	O15130	835
NPVF	GNRH1	P01148	807
NPVF	QRFP	P83859	764
NPVF	PRLH	P81277	716
NPVF	TAC3	Q9UHF0	708
NPVF	HCRT	O43612	665
NPVF	POMC	P01189	604
NPVF	FSHB	P01225	543
NPVF	NPY	P01303	542
NPVF	LEP	P41159	527
NPVF	CRH	P06850	521

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NPVF	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SGTA	NPVF	psi-mi:“MI:0915”(physical association)	0.560
NPVF	ABL1	psi-mi:“MI:0915”(physical association)	0.400
NPVF	FYN	psi-mi:“MI:0915”(physical association)	0.400
NCK1	NPVF	psi-mi:“MI:0915”(physical association)	0.400
NPVF	ACTA2	psi-mi:“MI:0915”(physical association)	0.400
NPVF	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
NPVF	SGTA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): NPVF (Two-hybrid), UBQLN2 (Two-hybrid), ACTA2 (Affinity Capture-MS)

ESM2 similar proteins: A8CL69, B2KKR4, B2ZB95, B2ZB96, B2ZB98, B2ZB99, B2ZBA0, B2ZBA1, C0HKS6, C0HKY1, C0HL17, C3Z6E6, D6WT67, E1ZXU8, E1ZZF9, E2AFK9, E2AYH6, G7NYP9, O02036, O18641, O45027, O76818, P01360, P01361, P01362, P07712, P08950, P09040, P09971, P11159, P16240, P17685, P17686, P19713, P20382, P32648, P35905, P49794, P56942, P61364

Diamond homologs: B2KKR4, Q9DGD4, Q9ESQ8, Q9ESQ9, Q9GM96, Q9HCQ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

551 predictions. Top by Δscore:

Variant	Effect	Δscore
7:25228298:TTACC:T	donor_loss	1.0000
7:25228299:TACCT:T	donor_loss	1.0000
7:25228300:A:AC	donor_gain	1.0000
7:25228301:C:CC	donor_gain	1.0000
7:25228301:CCT:C	donor_gain	1.0000
7:25225171:CTC:C	acceptor_gain	0.9900
7:25227022:CTAGG:C	acceptor_gain	0.9900
7:25227023:TAGG:T	acceptor_gain	0.9900
7:25227027:C:CC	acceptor_gain	0.9900
7:25228300:AC:A	donor_gain	0.9900
7:25228301:CC:C	donor_gain	0.9900
7:25225169:GTCTC:G	acceptor_gain	0.9800
7:25225174:CTAA:C	acceptor_loss	0.9800
7:25225175:T:A	acceptor_loss	0.9800
7:25225179:A:AC	acceptor_gain	0.9800
7:25227025:GG:G	acceptor_gain	0.9800
7:25228298:TTA:T	donor_gain	0.9800
7:25228299:TAC:T	donor_gain	0.9800
7:25228300:A:T	donor_gain	0.9800
7:25227023:TAGGC:T	acceptor_loss	0.9700
7:25227026:GC:G	acceptor_loss	0.9700
7:25227028:T:C	acceptor_loss	0.9700
7:25227033:T:TC	acceptor_gain	0.9700
7:25228297:CTTA:C	donor_gain	0.9700
7:25228300:ACCT:A	donor_gain	0.9700
7:25228301:CCTC:C	donor_gain	0.9700
7:25225174:C:CC	acceptor_gain	0.9600
7:25228296:ACTT:A	donor_gain	0.9600
7:25228301:CCTCA:C	donor_gain	0.9600
7:25226894:T:TG	acceptor_gain	0.9500

AlphaMissense

1296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:25226889:A:C	F92L	0.936
7:25226889:A:T	F92L	0.936
7:25226891:A:G	F92L	0.936
7:25226772:A:C	F131L	0.914
7:25226772:A:T	F131L	0.914
7:25226774:A:G	F131L	0.914
7:25226892:T:A	R91S	0.851
7:25226892:T:G	R91S	0.851
7:25228386:G:C	S18R	0.798
7:25228386:G:T	S18R	0.798
7:25228388:T:G	S18R	0.798
7:25226766:T:A	R133S	0.793
7:25226766:T:G	R133S	0.793
7:25226883:C:A	R94S	0.793
7:25226883:C:G	R94S	0.793
7:25226775:C:A	R130S	0.772
7:25226775:C:G	R130S	0.772
7:25226888:C:A	G93W	0.753
7:25226887:C:A	G93V	0.749
7:25226887:C:T	G93E	0.746
7:25228396:G:T	A15D	0.744
7:25226893:C:G	R91T	0.729
7:25226894:T:C	R91G	0.707
7:25226899:G:T	P89Q	0.702
7:25226899:G:C	P89R	0.695
7:25226896:A:G	L90S	0.694
7:25226902:A:G	L88S	0.680
7:25226770:C:T	G132E	0.677
7:25226888:C:G	G93R	0.671
7:25226888:C:T	G93R	0.671

dbSNP variants (sampled 300 via entrez): RS1000131366 (7:25226261 T>C), RS1000201414 (7:25224957 T>G), RS1000535366 (7:25225960 C>T), RS1002290058 (7:25227177 T>C), RS1003323780 (7:25229436 G>C), RS1003450320 (7:25224510 A>G), RS1003703598 (7:25229657 T>C), RS1004346402 (7:25224754 A>C), RS1004417662 (7:25228815 G>A), RS1004605436 (7:25224583 C>G,T), RS1004676015 (7:25225731 G>C,T), RS1005828732 (7:25229704 A>G), RS1006349931 (7:25226792 G>A,C), RS1006620892 (7:25227609 T>C), RS1006972533 (7:25230426 G>A)

Disease associations

OMIM: gene MIM:616984 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001949_7	Preeclampsia	8.000000e-06
GCST002817_9	Alzheimer’s disease in APOE e4- carriers	7.000000e-06
GCST006003_13	Triglyceride levels	2.000000e-09
GCST006298_2	Response to haloperidol in schizophrenia	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Endosulfan	increases expression	2
sodium arsenite	increases expression	1
Benzo(a)pyrene	decreases expression	1

Clinical trials (associated diseases)

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