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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCKBR
cholecystokinin B receptor
Chromosome 11 · 11p15.4
NCBI Gene: 887Ensembl: ENSG00000110148.10HGNC: HGNC:1571UniProt: E9PIC8
134PubMed Papers
20Diseases
4Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecholecystokinin receptor activityprotein bindingphospholipase C-activating G protein-coupled receptor signaling pathwaygastroesophageal reflux diseasePeptic ulcerpeptic ulcer diseaseduodenal ulcer
✦AI Summary

CCKBR (cholecystokinin B receptor) is a G protein-coupled receptor located on chromosome 11 that functions as both a gastrin and cholecystokinin receptor 1. The receptor activates multiple signaling pathways including Gαq/11-Ca2+, Gαs-cAMP, and β-arrestin-dependent mechanisms 2, with distinct conformations determining G protein selectivity 3. In the gastrointestinal system, CCKBR regulates gastric acid secretion, intestinal motility, and glucose absorption through PI3K/Akt signaling 4 and inhibits renal SGLT2-mediated glucose reabsorption via Erk/NF-κB pathways 5. In the central nervous system, CCKBR expression in the entorhinal cortex modulates memory and learning 3. Clinically, CCKBR variants are associated with peptic ulcer disease susceptibility through effects on Helicobacter pylori infection responses and gastric acid regulation 6. CCKBR+ cancer cells represent a stem cell-like subpopulation in gastric adenocarcinoma associated with poor prognosis and maintained through FOXO-mediated sialyltransferase activation 7. For Alzheimer's disease, selective Gq-biased CCKBR agonists reduce amyloid-β plaques and promote long-term potentiation via ADAM10 upregulation 3, while β-arrestin-biased agonists block potentiation and fear memory formation 2. The intestinal and renal gastrin/CCKBR axis shows therapeutic potential for type 2 diabetes management.

Sources cited
1
CCKBR (cholecystokinin B receptor) is a G protein-coupled receptor located on chromosome 11 that functions as both a gastrin and cholecystokinin receptor .
PMID: 7491953
2
The receptor activates multiple signaling pathways including Gαq/11-Ca2+, Gαs-cAMP, and β-arrestin-dependent mechanisms , with distinct conformations determining G protein selectivity .
PMID: 41360797
3
The receptor activates multiple signaling pathways including Gαq/11-Ca2+, Gαs-cAMP, and β-arrestin-dependent mechanisms , with distinct conformations determining G protein selectivity .
PMID: 41270732
4
In the gastrointestinal system, CCKBR regulates gastric acid secretion, intestinal motility, and glucose absorption through PI3K/Akt signaling and inhibits renal SGLT2-mediated glucose reabsorption via Erk/NF-κB pathways .
PMID: 39950948
5
In the gastrointestinal system, CCKBR regulates gastric acid secretion, intestinal motility, and glucose absorption through PI3K/Akt signaling and inhibits renal SGLT2-mediated glucose reabsorption via Erk/NF-κB pathways .
PMID: 39721589
6
Clinically, CCKBR variants are associated with peptic ulcer disease susceptibility through effects on Helicobacter pylori infection responses and gastric acid regulation .
PMID: 33608531
7
CCKBR+ cancer cells represent a stem cell-like subpopulation in gastric adenocarcinoma associated with poor prognosis and maintained through FOXO-mediated sialyltransferase activation .
PMID: 39164456
Disease Associationsⓘ20
gastroesophageal reflux diseaseOpen Targets
0.43Moderate
Peptic ulcerOpen Targets
0.41Moderate
peptic ulcer diseaseOpen Targets
0.29Weak
duodenal ulcerOpen Targets
0.25Weak
esophageal diseaseOpen Targets
0.23Weak
ovarian neoplasmOpen Targets
0.16Weak
mathematical abilityOpen Targets
0.16Weak
duodenal disorderOpen Targets
0.14Weak
stomach diseaseOpen Targets
0.14Weak
neoplasmOpen Targets
0.11Weak
Barrett's esophagusOpen Targets
0.10Weak
anxiety disorderOpen Targets
0.09Suggestive
type 2 diabetes mellitusOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
Zollinger-Ellison SyndromeOpen Targets
0.08Suggestive
influenzaOpen Targets
0.07Suggestive
melanomaOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
gastrointestinal stromal tumorOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_176875.4(CCKBR):c.701T>G (p.Met234Arg)Pathogenic
Hypercholesterolemia, familial, 1
☆☆☆☆2022→ Residue 234
View on ClinVar ↗
Drug Targets4
CI-988Phase II
Cholecystokinin B receptor antagonist
anxiety disorder
ITRIGLUMIDEPhase II
Cholecystokinin B receptor antagonist
anxiety disorder
NETAZEPIDEPhase II
Cholecystokinin B receptor antagonist
PROGLUMIDEApproved
Cholecystokinin receptor antagonist
gastroesophageal reflux disease
Related Genes
GASTProtein interaction97%PTK7Protein interaction92%TCIRG1Protein interaction82%CCKProtein interaction75%GRPProtein interaction75%GNAI2Protein interaction75%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
1%
Ovary
1%
Lung
0%
Liver
0%
Heart
0%
Gene Interaction Network
Click a node to explore
CCKBRGASTPTK7TCIRG1CCKGRPGNAI2
PROTEIN STRUCTURE
Preparing viewer…
PDB7F8W · 3.10 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.18LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.67–1.18]
RankingsWhere CCKBR stands among ~20K protein-coding genes
  • #3,447of 20,598
    Most Researched134 · top quartile
  • #916of 1,025
    FDA-Approved Drug Targets1
  • #4,798of 5,498
    Most Pathogenic Variants1
  • #12,368of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedCCKBR
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression.
PMID: 33608531
Nat Commun · 2021
1.00
2
Elucidating pathway-selective biased CCKBR agonism for Alzheimer's disease treatment.
PMID: 41270732
Cell · 2026
0.90
3
CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition.
PMID: 39164456
Cell Death Differ · 2024
0.80
4
Cholecystokinin receptors.
PMID: 7491953
Am J Physiol · 1995
0.70
5
Intestinal Gastrin/CCKBR Axis Protects against Type 2 Diabetes by Reducing Intestinal Glucose Absorption through the PI3K/Akt/eIF4B Signaling Pathway.
PMID: 39950948
Adv Sci (Weinh) · 2025
0.60