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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GHRL
ghrelin and obestatin prepropeptide
Chromosome 3 · 3p25.3
NCBI Gene: 51738Ensembl: ENSG00000157017.17HGNC: HGNC:18129UniProt: Q9UBU3
920PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of circadian sleep/wake cycle, non-REM sleepaxonresponse to estrogenprotein bindingobesitytype 2 diabetes mellitusSepsisneoplasm
✦AI Summary

GHRL encodes ghrelin and obestatin, a 28-amino acid peptide hormone primarily functioning as a ligand for the growth hormone secretagogue receptor (GHSR) 1. Beyond growth hormone stimulation, ghrelin regulates energy balance, appetite, gastric acid release, insulin secretion, and gastrointestinal motility 1. The hormone demonstrates broad metabolic effects, with elevated ghrelin levels associated with increased food intake and obesity; therapeutic interventions reducing ghrelin secretion correlate with decreased adiposity and improved lipid profiles 2. Mechanistically, ghrelin modulates multiple physiological pathways including inflammatory responses, circadian sleep-wake cycles, and corticotropin secretion 3. GHRL expression extends beyond classical endocrine tissues, with intronic long non-coding RNAs (lnc-GHRL-3:2 and lnc-GHRL-3:3) emerging as biomarkers in type 2 diabetes mellitus 4. In intervertebral disc degeneration, GHRL and related lipid metabolism pathways represent promising therapeutic targets 5. Clinically, GHRL polymorphisms influence antipsychotic-induced weight gain 6, though genetic variants show weak associations with cancer susceptibility 7. The ghrelin receptor exhibits distinct pharmacological profiles, with inverse agonists like PF-05190457 differentially modulating receptor signaling compared to endogenous agonists 8, suggesting therapeutic potential for GHRL-targeted interventions in metabolic and psychiatric disorders.

Sources cited
1
Ghrelin is a 28-amino acid peptide and GHSR ligand that regulates growth hormone release, energy balance, gastric acid, appetite, insulin secretion, and gastric motility
PMID: 28238732
2
Ghrelin reduction correlates with weight loss, decreased BMI, reduced waist circumference, and improved lipid profiles in obese women
PMID: 26093535
3
GHRL is identified as a medium-high priority frailty biomarker in the context of aging and age-related pathways
PMID: 30071357
4
GHRL intronic long non-coding RNAs (lnc-GHRL-3:2 and lnc-GHRL-3:3) are differentially expressed in type 2 diabetes mellitus and function as novel biomarkers
PMID: 32921167
5
LEAP2/GHRL expression represents a promising molecular therapeutic target for intervertebral disc degeneration
PMID: 37339697
6
GHRL -604 G/A polymorphism is associated with weight gain and BMI increase during atypical antipsychotic treatment
PMID: 22369141
7
GHRL and GHSR SNPs show weak associations with overall cancer risk across multiple cancer types
PMID: 25524946
8
Ghrelin receptor exhibits distinct binding modes for agonists versus inverse agonists, requiring specific polar networks for activation
PMID: 35027551
Disease Associationsⓘ20
obesityOpen Targets
0.27Weak
type 2 diabetes mellitusOpen Targets
0.12Weak
SepsisOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
obstructive sleep apneaOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
metabolic syndromeOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
acanthosis nigricansOpen Targets
0.11Weak
HypoglycemiaOpen Targets
0.11Weak
colitisOpen Targets
0.11Weak
gastric cancerOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.10Weak
chronic obstructive pulmonary diseaseOpen Targets
0.10Weak
rheumatoid arthritisOpen Targets
0.10Weak
neuroendocrine neoplasmOpen Targets
0.10Suggestive
acneOpen Targets
0.10Suggestive
polycystic ovary syndromeOpen Targets
0.10Suggestive
ulcerative colitisOpen Targets
0.10Suggestive
depressive disorderOpen Targets
0.10Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GH1Protein interaction100%GH2Protein interaction100%GHRProtein interaction100%GHRHProtein interaction100%GHRHRProtein interaction100%HCRTProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
17%
Lung
17%
Ovary
17%
Brain
13%
Heart
6%
Gene Interaction Network
Click a node to explore
GHRLGH1GH2GHRGHRHGHRHRHCRT
PROTEIN STRUCTURE
Preparing viewer…
PDB7NA7 · 2.70 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.82LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.18 [0.72–1.82]
RankingsWhere GHRL stands among ~20K protein-coding genes
  • #190of 20,598
    Most Researched920 · top 1%
  • #16,674of 17,882
    Most Constrained (LOEUF)1.82
Genes detectedGHRL
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Therapeutic effect of high-dose green tea extract on weight reduction: A randomized, double-blind, placebo-controlled clinical trial.
PMID: 26093535
Clin Nutr · 2016
1.00
2
Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.
PMID: 30071357
Ageing Res Rev · 2018
0.90
3
Relationship of Genetic Polymorphisms and Microbial Composition with Binge Eating Disorder: A Systematic Review.
PMID: 39057584
Healthcare (Basel) · 2024
0.82
4
Metabolomic signature and molecular profile of normal and degenerated human intervertebral disc cells.
PMID: 37339697
Spine J · 2023
0.80
5
Notum deacylates octanoylated ghrelin.
PMID: 33647468
Mol Metab · 2021
0.80