GPR139

G-protein coupled receptor 139 (GPC139) is a protein that in humans is encoded by the GPR139 gene.^[5][6] Research has shown that mice with loss of GCP139 experience schizophrenia-like symptomatology that is rescued with the dopamine receptor antagonist haloperidol and the μ-opioid receptor antagonist naltrexone.^[7][8]

GPR139
Identifiers
Aliases	GPR139, GPRg1, PGR3, G protein-coupled receptor 139
External IDs	OMIM: 618448; MGI: 2685341; HomoloGene: 45860; GeneCards: GPR139; OMA:GPR139 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p12.3 Start 20,028,239 bp[1] End 20,073,890 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F2 Start 118,739,970 bp[2] End 118,783,826 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle caudate nucleus putamen nucleus accumbens hypothalamus bone marrow substantia nigra pituitary gland C1 segment muscle tissue Top expressed in lumbar spinal ganglion habenula medial vestibular nucleus deep cerebellar nuclei mammillary body dorsal tegmental nucleus dorsomedial hypothalamic nucleus lateral hypothalamus central gray substance of midbrain embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity protein dimerization activity signal transducer activity neuropeptide receptor activity Cellular component integral component of membrane plasma membrane membrane Biological process G protein-coupled receptor signaling pathway phospholipase C-activating G protein-coupled receptor signaling pathway neuropeptide signaling pathway signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 124274 209776 Ensembl ENSG00000180269 ENSMUSG00000066197 UniProt Q6DWJ6 Q80UC8 RefSeq (mRNA) NM_001002911 NM_001318483 NM_001024138 RefSeq (protein) NP_001002911 NP_001305412 NP_001019309 Location (UCSC) Chr 16: 20.03 – 20.07 Mb Chr 7: 118.74 – 118.78 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

GPR139 is activated by L-tryptophan and L-phenylalanine, though only at relatively high concentrations,^[9] but in 2025, GPR139 was identified as a novel opioid receptor, specifically of dynorphins.^[10]

Ligands

Agonists

• JNJ-63533054
• Zelatriazin (TAK-41), (NBI-1065846) a potent, and GPR139 receptor selective agonist ^[11] which was in clinical trials to gauge the efficacy for treating psychiatric conditions such as major depressive disorder and the negative symptoms of schizophrenia, but was later dropped from development.
• TC-O 9311 [444932-31-4]

Antagonists

• JNJ-3792165