PRLH

Summary

PRLH (prolactin releasing hormone, HGNC:17945) is a protein-coding gene on chromosome 2q37.3, encoding Prolactin-releasing peptide (P81277). Stimulates prolactin (PRL) release and regulates the expression of prolactin through its receptor GPR10.

Predicted to enable neuropeptide hormone activity and prolactin-releasing peptide receptor binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway; feeding behavior; and response to peptide hormone. Predicted to act upstream of or within several processes, including fat cell differentiation; reduction of food intake in response to dietary excess; and response to insulin. Predicted to be located in cytoplasm.

Source: NCBI Gene 51052 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• Druggable target: yes
• MANE Select transcript: NM_015893

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17945
Approved symbol	PRLH
Name	prolactin releasing hormone
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	PRH
Ensembl gene	ENSG00000071677
Ensembl biotype	protein_coding
OMIM	602663
Entrez	51052

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000165524, ENST00000851003

RefSeq mRNA: 1 — MANE Select: NM_015893 NM_015893

CCDS: CCDS2519

Canonical transcript exons

ENST00000165524 — 2 exons

Exon	Start	End
ENSE00004283283	237567012	237567175
ENSE00004283286	237566574	237566673

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 90.99.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	90.99	silver quality
tendon of biceps brachii	UBERON:0008188	77.61	gold quality
parotid gland	UBERON:0001831	67.47	gold quality
heart right ventricle	UBERON:0002080	66.79	gold quality
endothelial cell	CL:0000115	65.99	silver quality
triceps brachii	UBERON:0001509	64.62	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.52	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	64.30	gold quality
pons	UBERON:0000988	62.23	gold quality
medial globus pallidus	UBERON:0002477	62.09	gold quality
cartilage tissue	UBERON:0002418	61.63	gold quality
globus pallidus	UBERON:0001875	60.59	gold quality
quadriceps femoris	UBERON:0001377	59.79	gold quality
vastus lateralis	UBERON:0001379	59.45	gold quality
vena cava	UBERON:0004087	59.18	gold quality
periodontal ligament	UBERON:0008266	59.02	silver quality
ileal mucosa	UBERON:0000331	58.66	silver quality
body of tongue	UBERON:0011876	58.53	gold quality
decidua	UBERON:0002450	58.38	gold quality
right atrium auricular region	UBERON:0006631	57.86	gold quality
skin of hip	UBERON:0001554	57.54	silver quality
esophagus squamous epithelium	UBERON:0006920	57.54	gold quality
cardiac atrium	UBERON:0002081	57.30	gold quality
epithelium of esophagus	UBERON:0001976	56.94	gold quality
nasal cavity epithelium	UBERON:0005384	56.76	gold quality
epithelial cell of pancreas	CL:0000083	56.56	silver quality
middle temporal gyrus	UBERON:0002771	56.42	gold quality
trabecular bone tissue	UBERON:0002483	55.95	gold quality
upper leg skin	UBERON:0004262	54.82	gold quality
epithelium of bronchus	UBERON:0002031	53.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• PrRP has a likely role in pheochromocytomas, based on its high expression in tumor tissue (PMID:12126742)
• Review discusses the ancestral relationship between prolactin-releasing hormone and the C-terminal RF-motif amide precursor peptide (C-RF). (PMID:15891064)
• Data indicate that formation of a primarily alpha-helical C-terminal region of prolactin releasing peptide (PrRP) is critical for receptor activation. (PMID:23426574)
• This study demonstrates that palm(11)-PrRP31 positively affects feeding and leptin-related hypothalamic signaling. (PMID:29233862)
• Reproductive Regulation of PrRPs in Teleost: The Link Between Feeding and Reproduction. (PMID:34803923)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prlh2	ENSDARG00000071735
mus_musculus	Prlh	ENSMUSG00000090550
rattus_norvegicus	Prlh	ENSRNOG00000019871

Protein

Protein identifiers

Prolactin-releasing peptide — P81277 (reviewed: P81277)

Alternative names: Prolactin-releasing hormone

All UniProt accessions (2): P81277, Q53QV7

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates prolactin (PRL) release and regulates the expression of prolactin through its receptor GPR10. May stimulate lactotrophs directly to secrete PRL.

Subcellular location. Secreted.

Tissue specificity. Medulla oblongata and hypothalamus.

RefSeq proteins (1): NP_056977* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026194	PrRP	Family

Pfam: PF15172

UniProt features (6 total): peptide 2, signal peptide 1, propeptide 1, modified residue 1, helix 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9K27	ELECTRON MICROSCOPY	2.68
8ZPT	ELECTRON MICROSCOPY	2.96
8ZPS	ELECTRON MICROSCOPY	2.97
9K26	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P81277-F1	66.37	0.16

Antibody-complex structures (SAbDab): 4 — 8ZPS, 8ZPT, 9K26, 9K27

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 (1): 53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors

MSigDB gene sets: 59 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BEHAVIOR, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_GROWTH, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_MULTICELLULAR_ORGANISM_GROWTH, GOBP_EATING_BEHAVIOR, GOBP_RESPONSE_TO_INSULIN, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_HORMONE, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (14): tissue homeostasis (GO:0001894), reduction of food intake in response to dietary excess (GO:0002023), energy reserve metabolic process (GO:0006112), lipid metabolic process (GO:0006629), G protein-coupled receptor signaling pathway (GO:0007186), feeding behavior (GO:0007631), response to glucose (GO:0009749), response to insulin (GO:0032868), regulation of multicellular organism growth (GO:0040014), response to peptide hormone (GO:0043434), fat cell differentiation (GO:0045444), autonomic nervous system development (GO:0048483), response to dietary excess (GO:0002021), eating behavior (GO:0042755)

GO Molecular Function (3): hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), prolactin-releasing peptide receptor binding (GO:0031861)

GO Cellular Component (2): extracellular region (GO:0005576), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
response to dietary excess	1
eating behavior	1
energy derivation by oxidation of organic compounds	1
primary metabolic process	1
G protein-coupled receptor activity	1
signal transduction	1
behavior	1
response to hexose	1
response to peptide hormone	1
multicellular organism growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
cell differentiation	1
nervous system development	1
system development	1
response to nutrient levels	1
energy homeostasis	1
feeding behavior	1
receptor ligand activity	1
hormone activity	1
neuropeptide activity	1
neuropeptide receptor binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRLH	PRLHR	P49683	996
PRLH	NPFF	O15130	941
PRLH	NPFFR2	Q9Y5X5	794
PRLH	QRFP	P83859	783
PRLH	PRL	P01236	749
PRLH	NPVF	Q9HCQ7	716
PRLH	NPY	P01303	691
PRLH	GRIP2	Q9C0E4	668
PRLH	NPY1R	P25929	664
PRLH	GRAP2	O75791	661
PRLH	SOS2	Q07890	636
PRLH	NPFFR1	Q9GZQ6	600
PRLH	GRB2	P29354	597
PRLH	LCK	P06239	583
PRLH	GRAP	Q13588	582

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O00230, O00253, O14836, O46541, O62827, O77559, P01160, P01169, P07499, P0C8A3, P0C8S2, P0CG36, P0CG37, P13204, P16859, P18104, P23582, P24393, P35318, P47851, P49192, P51461, P53366, P55206, P55207, P56283, P56388, P56413, P56473, P81172, P81277, P84715, P97297, Q5CZK2, Q5NVR8, Q61839, Q62715, Q62716, Q6PAL1, Q7TNK8

Diamond homologs: P81264, P81277, P81278, Q8WN12

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

110 predictions. Top by Δscore:

Variant	Effect	Δscore
2:237566671:GCA:G	donor_gain	1.0000
2:237566674:G:GG	donor_gain	1.0000
2:237566669:CCGCA:C	donor_gain	0.9900
2:237566670:CGCA:C	donor_gain	0.9900
2:237566671:GCAG:G	donor_gain	0.9900
2:237566672:CA:C	donor_gain	0.9900
2:237566673:AG:A	donor_loss	0.9900
2:237566675:T:A	donor_loss	0.9900
2:237566676:GAGT:G	donor_loss	0.9800
2:237566677:AGTG:A	donor_loss	0.9700
2:237566642:T:TA	donor_gain	0.9400
2:237566677:A:AG	donor_gain	0.9300
2:237566678:G:GG	donor_gain	0.9300
2:237566787:G:T	donor_gain	0.9100
2:237567010:A:AG	acceptor_gain	0.9000
2:237567011:G:GG	acceptor_gain	0.9000
2:237567006:TTCCA:T	acceptor_loss	0.8300
2:237567007:TCCA:T	acceptor_loss	0.8300
2:237567008:CCAGC:C	acceptor_loss	0.8300
2:237567009:CAGCC:C	acceptor_loss	0.8300
2:237567010:A:G	acceptor_loss	0.8300
2:237567011:G:GT	acceptor_loss	0.8300
2:237567011:GCCC:G	acceptor_gain	0.8200
2:237566694:C:A	donor_gain	0.8100
2:237567011:GCCCC:G	acceptor_gain	0.8000
2:237567011:GC:G	acceptor_gain	0.7800
2:237567011:GCC:G	acceptor_gain	0.7800
2:237566787:G:GT	donor_gain	0.7700
2:237566997:CTCTT:C	acceptor_loss	0.7500
2:237566998:TCTTT:T	acceptor_loss	0.7500

AlphaMissense

542 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:237567068:T:C	F53L	0.973
2:237567070:C:A	F53L	0.973
2:237567070:C:G	F53L	0.973
2:237567051:T:C	I47T	0.948
2:237567034:G:C	W41C	0.940
2:237567034:G:T	W41C	0.940
2:237567036:A:G	Y42C	0.926
2:237567035:T:C	Y42H	0.913
2:237567036:A:C	Y42S	0.907
2:237567032:T:A	W41R	0.890
2:237567032:T:C	W41R	0.890
2:237567063:G:A	G51D	0.874
2:237567055:G:C	R48S	0.871
2:237567055:G:T	R48S	0.871
2:237567065:C:A	R52S	0.867
2:237567044:C:A	R45S	0.865
2:237567063:G:T	G51V	0.859
2:237567069:T:G	F53C	0.859
2:237567072:G:A	G54D	0.854
2:237567051:T:G	I47S	0.852
2:237567054:G:T	R48M	0.848
2:237567068:T:A	F53I	0.846
2:237567035:T:G	Y42D	0.836
2:237567072:G:T	G54V	0.836
2:237567062:G:C	G51R	0.825
2:237567068:T:G	F53V	0.818
2:237567054:G:C	R48T	0.808
2:237567062:G:T	G51C	0.808
2:237567035:T:A	Y42N	0.807
2:237566601:T:C	C10R	0.802

dbSNP variants (sampled 300 via entrez): RS1000121219 (2:237565200 A>G,T), RS1000182244 (2:237565170 C>T), RS1000567739 (2:237565835 C>A), RS1003428990 (2:237566240 C>A,T), RS1004459168 (2:237565601 A>G), RS1006425898 (2:237566502 C>T), RS1006933197 (2:237566972 G>A,C,T), RS1007091935 (2:237564701 G>A,C,T), RS1007420763 (2:237565566 C>G,T), RS1008641230 (2:237565861 ACAT>A), RS1009004921 (2:237565682 TAC>T,TACAC,TACACAC), RS1009559127 (2:237567625 C>G), RS1010328426 (2:237565008 G>A,C,T), RS1010654446 (2:237566776 G>A,C), RS1010728614 (2:237564879 T>C)

Disease associations

OMIM: gene MIM:602663 | 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): CHEMBL4523266 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.68	Ki	2.1	nM	CHEMBL5082678

PubChem BioAssay actives

1 with measured affinity, of 13 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-4-[[(2S,3S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	1820166: Displacement of [3H]-PrRP-20 from human PrRP receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0021	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	affects expression	1
Particulate Matter	increases abundance, increases expression	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
CHEMBL5042869	Binding	Displacement of [3H]-PrRP-20 from human PrRP receptor expressed in CHO cells by TopCount scintillation counting method	Identification of an N-acylated-DArg-Leu-NH2 Dipeptide as a Highly Selective Neuropeptide FF1 Receptor Antagonist That Potently Prevents Opioid-Induced Hyperalgesia. — J Med Chem

Clinical trials (associated diseases)

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