Protein / target
Glucagon receptor
Protein at a glance
Biological role
Guanyl-nucleotide exchange factor activity
Primary system
Endocrine & metabolic
Strongest disease association
GCGR-related hyperglucagonemia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 11 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
G protein-coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:32193322, PubMed:38346960). Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system
Subcellular location
Domains and Gene Ontology detail (16)Hide
Gene Ontology
- Cmembrane
- Cplasma membrane
- Fglucagon receptor activity
- Fguanyl-nucleotide exchange factor activity
- Fpeptide hormone binding
- Padenylate cyclase-activating G protein-coupled receptor signaling pathway
- Padenylate cyclase-modulating G protein-coupled receptor signaling pathway
- Pcell surface receptor signaling pathway
- Pcellular response to glucagon stimulus
- Pcellular response to starvation
- Pgeneration of precursor metabolites and energy
- Pglucose homeostasis
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
G protein-coupled signalling
- ·G protein-coupled receptor for glucagon that plays a central role in the regulation of b…
- ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
- ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
Transcriptional regulation
- ·positive regulation of gene expression
View underlying pathways (4)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Glucagon receptor agonist
Appears in clinical studies involving Hypoglycemia, diabetes mellitus, type 1 diabetes mellitus, Hyperglycemia
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 455 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 14 total
diabetes mellitus · Hypoglycemia · type 1 diabetes mellitus
type 2 diabetes mellitus · type 2 diabetes mellitus · type 1 diabetes mellitus
type 2 diabetes mellitus
Hypoglycemia · diabetes mellitus · type 1 diabetes mellitus
type 1 diabetes mellitus · type 1 diabetes mellitus · type 1 diabetes mellitus
type 2 diabetes mellitus · metabolic dysfunction-associated steatotic liver disease · metabolic dysfunction-associated steatohepatitis
type 2 diabetes mellitus · type 2 diabetes mellitus · chronic kidney disease
Hypoglycemia · type 1 diabetes mellitus · congenital isolated hyperinsulinism
type 2 diabetes mellitus · type 2 diabetes mellitus
Obesity · cardiovascular disorder · obesity disorder
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- Product recall
Recall (Not Yet Classified): GLUCAGON
- Product recall
Recall (Class II): GLUCAGON
- New publicationGLP-1 Receptor Agonists.
- New publicationGLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective.
- New publicationGlucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.
- New publicationNeuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion.
- New publicationIncretin and glucagon receptor polypharmacology in chronic kidney disease.
- New publicationGLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion.
- New publicationDose-response effects on HbA<sub>1c</sub> and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial.
- New publicationResults from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity.
- New publicationMetabolic regulation of glucagon secretion.
- New publicationThe role of glucagon after bariatric/metabolic surgery: much more than an "anti-insulin" hormone.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.