GPR12

Chr 13

G protein-coupled receptor 12

Also known as: GPCR12, GPCR21, PPP1R84

NCBI Gene: 2835 ENSG00000132975 UniProt: P47775

GPR12 encodes a brain-specific G protein-coupled receptor that regulates neurite outgrowth and lipid/carbohydrate metabolism through constitutive G(s)-mediated signaling and cyclic AMP production. The gene has moderate constraint against loss-of-function variants (LOEUF 0.708), but no definitive human disease associations have been established in the provided data. Clinical significance of GPR12 variants in pediatric neurological disorders remains to be determined.

ResearchSummary from RefSeq, UniProt

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to act upstream of or within G protein-coupled receptor signaling pathway and intracellular calcium ion homeostasis. Predicted to be located in membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

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

0.71

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.362

Z-score 2.14

OE 0.22 (0.09–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.83Z-score

OE missense 0.64 (0.55–0.74)

127 obs / 199.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.09–0.71)

0≤0.351.4

Missense OE?0.64 (0.55–0.74)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 2 / 8.9Missense obs/exp: 127 / 199.6Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in GPR12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

355 rare PASS variants

Rare truncating (LoF)

1 in 6,100

21 rare PASS variants

Rare synonymous (reference)

1 in 210

217 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR12. 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 440	1 in 5,400
South Asian	~43k	1 in 240	1 in 7,000
Remaining (unassigned)	~30k	1 in 210	none seen
European (Finnish)	~27k	1 in 950	≈ 1 in 26,000
Admixed American	~22k	1 in 330	≈ 1 in 7,500
African / African American	~21k	1 in 350	≈ 1 in 6,400
East Asian	~20k	1 in 270	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,000	none seen
Middle Eastern	~2,884	1 in 120	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 ↓