GPR139

Chr 16

G protein-coupled receptor 139

ENSG00000180269UniProt: Q6DWJ6

Orphan receptor. Seems to act through a G(q/11)-mediated pathway

0
ClinVar variants
0
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— GPR139
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.87LOEUF
pLI 0.037
Z-score 1.87
OE 0.38 (0.19–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.91Z-score
OE missense 0.82 (0.72–0.93)
166 obs / 202.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.19–0.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.72–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 4 / 10.6Missense obs/exp: 166 / 202.5Syn Z: -0.43

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GPR139 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GPR139, an Ancient Receptor and an Emerging Target for Neuropsychiatric and Behavioral Disorders.
Chan M et al.·Mol Neurobiol
2025Review
Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment.
Zethoven M et al.·Nat Commun
2022
Molecular insights into orphan G protein-coupled receptors relevant to schizophrenia.
Lu Y et al.·Br J Pharmacol
2024Review
Discovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia.
Reichard HA et al.·J Med Chem
2021
A Phase 2 Randomized Trial of NBI-1065846 (TAK-041) in Patients With Anhedonia Associated With Major Depressive Disorder: Results of the TERPSIS Study.
Benedetto SR et al.·J Clin Psychopharmacol
2025Clinical trial
Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.
Ren P et al.·Bioengineered
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools