GPR19

Chr 12

G protein-coupled receptor 19

NCBI Gene: 2842 ENSG00000183150 UniProt: Q15760 OMIM: 602927

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables G protein-coupled receptor activity. Involved in G protein-coupled receptor signaling pathway. Located in cilium. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.30 (0.14–0.68)

0≤0.351.4

Missense OE?0.73 (0.64–0.83)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 4 / 13.5Missense obs/exp: 167 / 228.7Syn Z: 0.93

Background carrier burden — how many people carry a rare variant somewhere in GPR19?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

450 rare PASS variants

Rare truncating (LoF)

1 in 3,800

45 rare PASS variants

Rare synonymous (reference)

1 in 200

189 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR19. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 3,900
South Asian	~43k	1 in 190	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 7,500
European (Finnish)	~27k	1 in 810	≈ 1 in 13,000
Admixed American	~22k	1 in 140	1 in 2,800
African / African American	~21k	1 in 170	1 in 3,600
East Asian	~20k	1 in 160	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 710	none seen
Middle Eastern	~2,884	1 in 180	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓