GPR19

Chr 12

G protein-coupled receptor 19

NCBI Gene: 2842ENSG00000183150UniProt: Q15760

GPR19 encodes a G-protein coupled receptor that regulates circadian rhythms and energy metabolism, particularly in the suprachiasmatic nucleus (master circadian clock), and modulates mitochondrial energy metabolism through adropin binding and p44/42-PDK4 signaling. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.68), but specific disease associations and inheritance patterns have not yet been established in humans. Further research is needed to determine the clinical significance of GPR19 variants in pediatric patients.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
45
P/LP submissions
0%
P/LP missense
0.68
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— GPR19
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 52 VUS of 112 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.104
Z-score 2.39
OE 0.30 (0.14–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.45Z-score
OE missense 0.73 (0.64–0.83)
167 obs / 228.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.14–0.68)
0≤0.351.4
Missense OE0.73 (0.64–0.83)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 4 / 13.5Missense obs/exp: 167 / 228.7Syn Z: 0.93
DN
0.76top 25%
GOF
0.78top 25%
LOF
0.2774th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic2
VUS52
Likely Benign5
Benign5
43
Pathogenic
2
Likely Pathogenic
52
VUS
5
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
2
0
2
VUS
0
48
4
0
52
Likely Benign
0
4
0
1
5
Benign
0
1
2
2
5
Total053513107

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GPR19 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients