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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPR142
G protein-coupled receptor 142
Chromosome 17 · 17q25.1
NCBI Gene: 350383Ensembl: ENSG00000257008.7HGNC: HGNC:20088UniProt: Q7Z601
11PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glucose homeostasisphospholipase C-activating G protein-coupled receptor signaling pathwayG protein-coupled receptor activityG protein-coupled receptor signaling pathwayMODYhyperinsulinism due to INSR deficiencyhyperinsulinism due to glucokinase deficiencyHereditary persistence of fetal hemoglobin - beta-thalassemia
✦AI Summary

GPR142 is a G protein-coupled receptor that functions as a selective sensor for aromatic amino acids, particularly L-tryptophan and L-phenylalanine, with L-tryptophan being the most potent agonist 12. Upon activation, GPR142 triggers both Gq and Gi protein-coupled signaling pathways 1. The receptor is expressed in pancreatic islets and gastrointestinal enteroendocrine cells, where it regulates glucose homeostasis by coordinating insulin and incretin hormone secretion in response to aromatic amino acid sensing 2. L-tryptophan activation of GPR142 stimulates glucose-dependent insulin secretion and GIP secretion from duodenal K cells, with both CASR and GPR142 contributing to amino acid-induced hormone secretion 3. Notably, GPR142 mediates tryptophan-induced β-cell regeneration through a gut microbiota-tryptophan metabolism-GLP-1 axis in type 2 diabetes models 4. Beyond metabolic regulation, GPR142 expression is directly upregulated by proinflammatory cytokines (TNF-α, IL-6, IL-1β) in ghrelin-producing cells, suggesting roles in inflammatory responses 5. These findings position GPR142 as a therapeutic target for metabolic diseases including type 2 diabetes 6.

Sources cited
1
GPR142 is a selective GPCR for L-tryptophan and L-phenylalanine that activates both Gq and Gi signaling pathways
PMID: 27104960
2
GPR142 controls tryptophan-induced insulin and incretin hormone secretion to improve glucose metabolism
PMID: 27322810
3
L-tryptophan upregulates GLP-1 production and promotes β-cell regeneration via GPR142 signaling in type 2 diabetic mice
PMID: 38471012
4
GPR142 and CASR contribute to amino acid-stimulated GIP secretion from human duodenal K cells
PMID: 39441374
5
GPR142 expression in ghrelin-producing cells is directly regulated by proinflammatory cytokines TNF-α, IL-6, and IL-1β
PMID: 39888273
6
GPR142 is involved in metabolic homeostasis and is a pharmacotherapeutic target for metabolic diseases
PMID: 38326623
Disease Associationsⓘ20
MODYOpen Targets
0.07Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.06Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.06Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.06Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.05Suggestive
exercise-induced hyperinsulinismOpen Targets
0.05Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.05Suggestive
hemoglobin H diseaseOpen Targets
0.05Suggestive
Combined pituitary hormone deficiencies, genetic formsOpen Targets
0.05Suggestive
hypoinsulinemic hypoglycemia and body hemihypertrophyOpen Targets
0.05Suggestive
hyperinsulinism-hyperammonemia syndromeOpen Targets
0.05Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
hyperinsulinemic hypoglycemia, familial, 2Open Targets
0.05Suggestive
hyperproinsulinemiaOpen Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.05Suggestive
hyperinsulinemic hypoglycemia, familial, 1Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRHRShared pathway50%OXGR1Shared pathway50%MLXIPShared pathway50%MLXShared pathway50%CCKARShared pathway33%GNG13Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Liver
26%
Ovary
21%
Bone Marrow
11%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
GPR142TRHROXGR1MLXIPMLXCCKARGNG13
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q7Z601
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.59LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.49–1.59]
RankingsWhere GPR142 stands among ~20K protein-coding genes
  • #16,772of 20,598
    Most Researched11
  • #15,644of 17,882
    Most Constrained (LOEUF)1.59
Genes detectedGPR142
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Gut Microbiota-Tryptophan Metabolism-GLP-1 Axis Participates in β-Cell Regeneration Induced by Dapagliflozin.
PMID: 38471012
Diabetes · 2024
1.00
2
Tryptophan-sensing receptor GPR142 expression levels are directly regulated by proinflammatory cytokines in ghrelin-producing cells.
PMID: 39888273
FEBS Open Bio · 2025
0.90
3
Sequence-structure based phylogeny of GPCR Class A Rhodopsin receptors.
PMID: 24503482
Mol Phylogenet Evol · 2014
0.80
4
GPCRs involved in metabolic diseases: pharmacotherapeutic development updates.
PMID: 38326623
Acta Pharmacol Sin · 2024
0.70
5
Cellular mechanisms governing glucose-dependent insulinotropic polypeptide secretion.
PMID: 31756367
Peptides · 2020
0.60