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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCKAR
cholecystokinin A receptor
Chromosome 4 · 4p15.2
NCBI Gene: 886Ensembl: ENSG00000163394.6HGNC: HGNC:1570UniProt: P32238
90PubMed Papers
20Diseases
5Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membranecholecystokinin receptor activityprotein bindingpeptide hormone bindingAbnormality of the skeletal systemgastroesophageal reflux diseasePeptic ulcerneurodegenerative disease
✦AI Summary

CCKAR (cholecystokinin A receptor) is a G protein-coupled receptor located on chromosome 4 that mediates the physiological actions of cholecystokinin (CCK) in both peripheral and central nervous systems 1. In the gastrointestinal tract, CCKAR is predominantly expressed in the gallbladder and small intestine, where it regulates gallbladder contraction and emptying, pancreatic enzyme secretion, and intestinal motility through phosphatidylinositol-calcium second messenger signaling 2. CCKAR exhibits approximately 1000-fold higher affinity for CCK than gastrin, distinguishing it from the CCK-B receptor 1. In the central nervous system, CCKAR contributes to regulation of satiety, anxiety, analgesia, and dopamine-mediated behaviors, with some evidence suggesting involvement in cognitive processes 1, 3. At the cellular level, CCKAR mediates sex hormone-responsive regulation of social behaviors in specific neuronal populations, including ventromedial hypothalamus neurons expressing estrogen receptor 1 that are essential for mating behavior in females 4. Clinically, CCKAR dysfunction is highly relevant to cholesterol gallstone disease; genetic variants in CCKAR are associated with increased gallstone susceptibility, and the gene has been identified as Lith13, a major gallstone susceptibility locus 2. CCKAR polymorphisms have also been investigated in relation to alcohol withdrawal-associated hallucinations 5. Naturally occurring CCKAR gene disruption in OLETF rats results in hyperglycemia, hyperinsulinemia, and obesity phenotypes resembling non-insulin-dependent diabetes mellitus 6.

Sources cited
1
CCKAR distribution, functions in GI tract and CNS, affinity for CCK and gastrin, receptor subtypes classification
PMID: 7491953
2
CCKAR expression in gallbladder and small intestine, role in gallbladder contraction and cholesterol absorption, association with gallstone disease, Lith13 identification
PMID: 33260332
3
VMHvlCckar/Esr1 cell type role in female mating behavior and sex-typical social behaviors
PMID: 35065713
4
CCKAR gene involvement in cognitive processes and intelligence
PMID: 27333929
5
CCKAR gene polymorphisms association with alcohol withdrawal hallucinations and delirium tremens
PMID: 12198366
6
CCKAR gene disruption in OLETF rats causes hyperglycemia, hyperinsulinemia, and obesity
PMID: 9332364
7
CCKAR chromosomal localization to human chromosome 4 and mouse chromosome 5
PMID: 7759110
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.50Moderate
gastroesophageal reflux diseaseOpen Targets
0.37Weak
Peptic ulcerOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.31Weak
irritable bowel syndromeOpen Targets
0.26Weak
ovarian neoplasmOpen Targets
0.18Weak
ankylosing spondylitisOpen Targets
0.17Weak
obesityOpen Targets
0.11Weak
AnxietyOpen Targets
0.08Suggestive
gallstonesOpen Targets
0.08Suggestive
dyspepsiaOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
influenzaOpen Targets
0.07Suggestive
attention deficit hyperactivity disorderOpen Targets
0.07Suggestive
hypertensionOpen Targets
0.06Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.06Suggestive
gallbladder disease 1Open Targets
0.05Suggestive
gastric carcinomaOpen Targets
0.05Suggestive
gallbladder diseaseOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets5
CE-326597Phase II
Cholecystokinin A receptor agonist
obesity
CERULETIDEApproved
Cholecystokinin A receptor agonist
DEXLOXIGLUMIDEPhase III
Cholecystokinin A receptor antagonist
irritable bowel syndrome
PROGLUMIDEApproved
Cholecystokinin receptor antagonist
gastroesophageal reflux disease
SINCALIDEPhase III
Cholecystokinin A receptor agonist
Related Genes
GNB1Protein interaction99%GNAQProtein interaction97%GASTProtein interaction97%GCGProtein interaction96%PTK7Protein interaction95%CCL28Protein interaction95%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
33%
Lung
0%
Ovary
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
CCKARGNB1GNAQGASTGCGPTK7CCL28
PROTEIN STRUCTURE
Preparing viewer…
PDB7MBX · 1.95 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.01LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.51–1.01]
RankingsWhere CCKAR stands among ~20K protein-coding genes
  • #5,290of 20,598
    Most Researched90
  • #611of 1,025
    FDA-Approved Drug Targets2
  • #9,859of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedCCKAR
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A functional cellular framework for sex and estrous cycle-dependent gene expression and behavior.
PMID: 35065713
Cell · 2022
1.00
2
Cholecystokinin receptors.
PMID: 7491953
Am J Physiol · 1995
0.90
3
An Update on the Lithogenic Mechanisms of Cholecystokinin a Receptor (CCKAR), an Important Gallstone Gene for
PMID: 33260332
Genes (Basel) · 2020
0.80
4
The molecular basis for high affinity of a universal ligand for human bombesin receptor (BnR) family members.
PMID: 22828605
Biochem Pharmacol · 2012
0.70
5
PMID: 20641941
0.60