Gpr52

G protein-coupled receptor 52

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: CP (Caudoputamen) · Positive regions: 7/554

45.4Discovery Score
39.9Targetability Score
CEvidence grade C
What this means: Gpr52: predicted fine-region profile is strict-exclusive, with 7 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in CP: evidence, prediction, innovation

Gene function
Gpr52 encodes an orphan class-A GPCR that is constitutively active and couples to Gs, raising cAMP without a known endogenous ligand. Its coding sequence lies within an intron of Rabgap1l. Downstream it acts through cAMP but in a PKA-independent, Rab39B-dependent route that stabilises huntingtin protein.
Region function
The caudoputamen is the basal-ganglia input nucleus whose D1 and D2 spiny projection neurons drive action selection, habit learning and reward; D2 neurons here are the cells lost earliest in Huntington's disease.
Published in this region
direct Yao et al. 2015 (eLife) showed Gpr52 is striatum-enriched and concentrated in D2 medium spiny neurons, stabilising wild-type and mutant huntingtin via cAMP-dependent, PKA-independent Rab39B signalling; heterozygous knockout lowered huntingtin selectively in striatum of HD knock-in mice, and Gpr52 reduction rescued motor deficits in fly HD models and neuronal loss in patient iPSC neurons. Wang et al. 2021 (J Med Chem) developed the antagonist Comp-43, which lowered mutant huntingtin and improved phenotypes in HdhQ140 mice.
Predicted function
Prediction: constitutive Gs activity of GPR52 sets a tonic cAMP set-point in D2 caudoputamen neurons, amplifying A2A-like signalling and opposing D2 inhibition, so agonists (FTBMT, 3-BTBZ) should suppress hyperlocomotion with antipsychotic-like effects while antagonists lower huntingtin and disinhibit indirect-pathway output. Knockout should reduce striatal cAMP tone, increase locomotor responses to dopamine agonists and slow degeneration in HD models.
Innovation
★★☆☆☆ 2/5 GPR52 is already a well-developed striatal drug target for Huntington's disease and psychosis, though its normal circuit role in caudoputamen behaviour remains thinly characterised.
Tools
Gpr52 knockout mice, agonists FTBMT and 3-BTBZ, antagonist Comp-43 (Wang et al. 2021), striatal D2-neuron access via Adora2a-Cre (MMRRC 036158-UCD) and Drd2-Cre, published GPR52 cryo-EM structures for structure-based ligand design.
References

Direct evidence located at the region

No Allen ISH section could be located at this region's centroid for the recorded experiments.

Look it up yourself: Allen Mouse Brain ISH for Gpr52Allen reference atlas: CP (structure 672)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Gpr52" or by parcellation_substructure "CP")All genes confined to CP + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
CP MERFISH region locator
Real single-cell MERFISH coordinates for the CP (Caudoputamen) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

Gpr52 regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

CP
0.975
ACB
0.491
OT
0.437
PMd
0.272
MMp
0.267
MMm
0.26
TMd
0.241
PMv
0.196
MMme
0.179
PVT
0.176
MMl
0.176
LA
0.174
RE
0.163
COApm
0.148
BLAa
0.146
MH
0.144
POL
0.141
FS
0.136
ILA2/3
0.132
IMD
0.13

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.352
Top-region fraction
0.137
Filter status
PASS

Interpretation limits