QRFP

Summary

QRFP (pyroglutamylated RFamide peptide, HGNC:29982) is a protein-coding gene on chromosome 9q34.12, encoding Orexigenic neuropeptide QRFP (P83859). Stimulates feeding behavior, metabolic rate and locomotor activity and increases blood pressure.

This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. The encoded products are members of the RFamide family of neuropeptides, characterized by their common protein C-terminus consisting of an arginine (R) and an amidated phenylalanine (F). These products include the neuropeptides 26RFa and the N-terminally extended form, 43RFa. Both of these neuropeptides bind to the pyroglutamylated RFamide peptide receptor (QRFPR) and may regulate blood pressure, reproduction and food intake in rodents.

Source: NCBI Gene 347148 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• MANE Select transcript: NM_198180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29982
Approved symbol	QRFP
Name	pyroglutamylated RFamide peptide
Location	9q34.12
Locus type	gene with protein product
Status	Approved
Aliases	26RFa, P518, prepro-26RFa
Ensembl gene	ENSG00000188710
Ensembl biotype	protein_coding
OMIM	609795
Entrez	347148

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000343079, ENST00000623824

RefSeq mRNA: 1 — MANE Select: NM_198180 NM_198180

CCDS: CCDS6936

Canonical transcript exons

ENST00000623824 — 3 exons

Exon	Start	End
ENSE00003757521	130895697	130895981
ENSE00003758115	130896577	130896812
ENSE00003758863	130892707	130893838

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 71.57.

Top tissues by expression

131 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	71.57	silver quality
lower esophagus mucosa	UBERON:0035834	70.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.35	gold quality
mucosa of transverse colon	UBERON:0004991	68.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	67.30	gold quality
stromal cell of endometrium	CL:0002255	65.26	gold quality
popliteal artery	UBERON:0002250	65.03	gold quality
tibial artery	UBERON:0007610	64.96	gold quality
sural nerve	UBERON:0015488	64.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	63.87	gold quality
lower esophagus	UBERON:0013473	63.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.49	gold quality
colon	UBERON:0001155	62.97	gold quality
transverse colon	UBERON:0001157	62.38	gold quality
left coronary artery	UBERON:0001626	62.13	gold quality
descending thoracic aorta	UBERON:0002345	61.61	gold quality
fundus of stomach	UBERON:0001160	61.10	gold quality
urinary bladder	UBERON:0001255	60.34	gold quality
intestine	UBERON:0000160	60.00	gold quality
mucosa of stomach	UBERON:0001199	59.91	gold quality
thoracic aorta	UBERON:0001515	59.91	gold quality
esophagus	UBERON:0001043	59.58	gold quality
ascending aorta	UBERON:0001496	59.56	gold quality
right coronary artery	UBERON:0001625	59.55	gold quality
prostate gland	UBERON:0002367	58.78	gold quality
adenohypophysis	UBERON:0002196	58.31	gold quality
body of stomach	UBERON:0001161	57.69	gold quality
left uterine tube	UBERON:0001303	57.43	gold quality
monocyte	CL:0000576	57.35	gold quality
leukocyte	CL:0000738	56.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, LHX2, USF2

Literature-anchored findings (GeneRIF, showing 9)

• P518 exhibited high affinity for SP9155. The peptide P518 precursor gene is predominantly expressed in various brain regions, coronary arteries, thyroid and parathyroid glands, large intestine, colon, bladder, testes, and prostate. (PMID:12714592)
• Solution conformation of 26RFa by using two-dimensional NMR spectroscopy in different media was investigated. (PMID:15808908)
• A bioinformatic search for peptides related to frog 26RFa reveals the presence of homologous sequences in the human genome. (PMID:15891009)
• Characterization of 26RFa-related peptides showed that two distinct molecular forms of 26RFa are present in the human hypothalamus and spinal cord, i.e. 26RFa and an N-terminally elongated form of 43 amino acids designated 43RFa. (PMID:16899066)
• Results suggest that GPR103b and QRFP work in an autocrine/paracrine manner to regulate adipogenesis. (PMID:20534693)
• High levels of circulating 26RFa observed in anorexia nervosa patients might reflect an adaptive mechanism of the organism to promote energy intake and to increase fat stores in response to undernutrition. (PMID:22466335)
• Data indicate that 26RFa may participate to the development of prostate cancer at the androgen independent state by promoting the neuroendocrine differentiation and the migration of cancer cells via autocrine/paracrine mechanisms. (PMID:22863147)
• we show a moderate positive correlation between plasma 26RFa levels and insulin in patients with diabetes. Plasma 26RFa increases in response to glucose tolerance test. 26RFa and its receptor GPR103 are present in human pancreatic beta-cells and gut. (PMID:25858563)
• The expression of both QRFP and GPR103 at the gene and protein level was higher in human prostate cancer tissue samples compared to control and benign prostatic hyperplasia samples. (PMID:30483810)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Qrfp	ENSMUSG00000043102
rattus_norvegicus	Qrfp	ENSRNOG00000046473

Protein

Protein identifiers

Orexigenic neuropeptide QRFP — P83859 (reviewed: P83859)

Alternative names: P518

All UniProt accessions (1): P83859

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates feeding behavior, metabolic rate and locomotor activity and increases blood pressure. May have orexigenic activity. May promote aldosterone secretion by the adrenal gland.

Subunit / interactions. Ligand for the G-protein coupled receptor QRFPR/GPR103.

Subcellular location. Secreted.

Tissue specificity. Expressed widely in the brain with highest expression levels in the cerebellum, medulla, pituitary, retina, vestibular nucleus, and white matter. Also expressed in the bladder, colon, coronary artery, parathyroid gland, prostate, testis, and thyroid.

Similarity. Belongs to the RFamide neuropeptide family.

RefSeq proteins (1): NP_937823* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024565	P518	Family

Pfam: PF11109

UniProt features (7 total): modified residue 2, signal peptide 1, propeptide 1, peptide 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8ZH8	ELECTRON MICROSCOPY	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P83859-F1	58.44	0.00

Antibody-complex structures (SAbDab): 1 — 8ZH8

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): 91, 133

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-389397	Orexin and neuropeptides FF and QRFP bind to their respective receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 46 (showing top): GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, NKX61_01, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_BEHAVIOR, GOBP_REGULATION_OF_FEEDING_BEHAVIOR, WTGAAAT_UNKNOWN, TGACATY_UNKNOWN, GOBP_GROOMING_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_BLOOD_PRESSURE, AACTTT_UNKNOWN, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, RFX1_02, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (5): neuropeptide signaling pathway (GO:0007218), grooming behavior (GO:0007625), locomotory behavior (GO:0007626), positive regulation of blood pressure (GO:0045777), regulation of feeding behavior (GO:0060259)

GO Molecular Function (4): neuropeptide hormone activity (GO:0005184), orexigenic neuropeptide QRFP receptor binding (GO:0031854), G protein-coupled receptor binding (GO:0001664), signaling receptor binding (GO:0005102)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
behavior	2
G protein-coupled receptor signaling pathway	1
regulation of blood pressure	1
feeding behavior	1
regulation of behavior	1
hormone activity	1
neuropeptide activity	1
neuropeptide receptor binding	1
signaling receptor binding	1
protein binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

537 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
QRFP	QRFPR	Q96P65	999
QRFP	NPFFR2	Q9Y5X5	904
QRFP	NPFFR1	Q9GZQ6	887
QRFP	PRLH	P81277	783
QRFP	GAL	P22466	783
QRFP	NPFF	O15130	778
QRFP	NPVF	Q9HCQ7	764
QRFP	NPY1R	P25929	746
QRFP	GNAQ	P50148	712
QRFP	PRLHR	P49683	680
QRFP	KISS1	Q15726	679
QRFP	KISS1R	Q969F8	622
QRFP	NMU	P48645	611
QRFP	HCRT	O43612	587
QRFP	SPX	Q9BT56	583

IntAct

0 interactions, top by confidence:

BioGRID (1): QRFP (Affinity Capture-RNA)

ESM2 similar proteins: D5J9S0, O00230, O46540, O46688, O77801, O97937, P01160, P01161, P01168, P01169, P01170, P01171, P05125, P07499, P07500, P07501, P09876, P16859, P16860, P24259, P26917, P27104, P27596, P33094, P41547, P49670, P55089, P56469, P60041, P60042, P61278, P61279, P68248, P83228, P83859, P83860, P87384, P87385, Q2XXL8, Q62949

Diamond homologs: P83683, P83859, P83860, P83862, Q8CE23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

287 predictions. Top by Δscore:

Variant	Effect	Δscore
9:130896575:ACC:A	donor_gain	1.0000
9:130896576:CCC:C	donor_gain	1.0000
9:130896636:T:TA	donor_gain	1.0000
9:130896637:C:A	donor_gain	1.0000
9:130895981:CCTT:C	acceptor_gain	0.9900
9:130896572:CCTA:C	donor_loss	0.9800
9:130896574:TACC:T	donor_loss	0.9800
9:130896575:AC:A	donor_gain	0.9800
9:130896576:C:G	donor_loss	0.9800
9:130896576:CC:C	donor_gain	0.9800
9:130896570:GACCT:G	donor_loss	0.9700
9:130896571:ACCTA:A	donor_loss	0.9700
9:130893795:A:T	acceptor_gain	0.9500
9:130893845:C:T	acceptor_gain	0.9500
9:130895980:CCCTT:C	acceptor_gain	0.9500
9:130896575:A:AC	donor_gain	0.9500
9:130896576:C:CC	donor_gain	0.9500
9:130893845:C:CT	acceptor_gain	0.9400
9:130895977:CTGCC:C	acceptor_gain	0.9400
9:130895984:T:C	acceptor_gain	0.9400
9:130893794:C:T	acceptor_gain	0.9300
9:130893798:G:T	acceptor_gain	0.9300
9:130895980:CCCT:C	acceptor_loss	0.9300
9:130895981:CC:C	acceptor_loss	0.9300
9:130895982:C:CA	acceptor_loss	0.9300
9:130896584:T:TA	donor_gain	0.9300
9:130893846:A:T	acceptor_gain	0.9200
9:130896585:C:A	donor_gain	0.9200
9:130895984:T:TC	acceptor_gain	0.9100
9:130896680:T:TA	donor_gain	0.8900

AlphaMissense

863 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:130893452:G:C	F129L	0.987
9:130893452:G:T	F129L	0.987
9:130893454:A:G	F129L	0.987
9:130893440:G:C	F133L	0.986
9:130893440:G:T	F133L	0.986
9:130893442:A:G	F133L	0.986
9:130893446:G:C	F131L	0.980
9:130893446:G:T	F131L	0.980
9:130893448:A:G	F131L	0.980
9:130893447:A:G	F131S	0.956
9:130893453:A:G	F129S	0.955
9:130893453:A:C	F129C	0.930
9:130893447:A:C	F131C	0.928
9:130893462:T:A	K126I	0.924
9:130893441:A:C	F133C	0.911
9:130893438:C:A	G134V	0.908
9:130893442:A:T	F133I	0.908
9:130893438:C:T	G134D	0.906
9:130893460:C:G	G127R	0.887
9:130893441:A:G	F133S	0.882
9:130893460:C:A	G127C	0.875
9:130893467:C:A	R124S	0.874
9:130893467:C:G	R124S	0.874
9:130893442:A:C	F133V	0.872
9:130893461:T:A	K126N	0.872
9:130893461:T:G	K126N	0.872
9:130893492:G:T	A116D	0.862
9:130893483:A:T	L119H	0.859
9:130893439:C:G	G134R	0.853
9:130893454:A:C	F129V	0.837

dbSNP variants (sampled 300 via entrez): RS1000034470 (9:130896821 T>C), RS1000165294 (9:130892942 G>A), RS1000271662 (9:130896984 G>A,C), RS1000411779 (9:130893137 CG>C), RS1000498652 (9:130893657 G>A), RS1000612023 (9:130898016 C>T), RS1001753442 (9:130895546 C>A,G), RS1001952192 (9:130895300 G>A), RS1002112482 (9:130897875 C>G), RS1002372430 (9:130894885 C>T), RS1002619483 (9:130898573 C>A,G), RS1003162950 (9:130894411 G>A), RS1003339782 (9:130897484 C>T), RS1003623086 (9:130897716 C>A,T), RS1003890878 (9:130898169 C>A,T)

Disease associations

OMIM: gene MIM:609795 | 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: yes

ChEMBL targets (1): CHEMBL5724595 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
aristolochic acid I	increases expression	1
propionaldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5723878	Binding	RLU of QRFP at 1.0 µM in the Aequorin PRESTO-Tango GPCRome screen	Data for DCP probe T-10430

Clinical trials (associated diseases)

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