Gpr63

Probable G protein-coupled receptor 63 (PSP24-2) (PSP24-beta)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: CA1sp (Field CA1, pyramidal layer) · Positive regions: 41/554

44.2Discovery Score
36.4Targetability Score
CEvidence grade C
What this means: Gpr63: fine CCF profile is region-biased toward CA1sp (top regions: CA1sp, CA2sp, CA1sr, CA1so, PF); this is a discovery lead, not direct proof.

Function in CA1sp: evidence, prediction, innovation

Gene function
GPR63 is a class-A orphan GPCR in the lysophospholipid-related branch. Niedernberg et al. 2003 identified sphingosine 1-phosphate and dioleoyl-phosphatidic acid as low-affinity agonists driving Ca2+ mobilisation, so it is treated as a lipid-sensing Gi/Gq receptor. Snedeker et al. 2019 additionally showed GPR63 localises to primary cilia and modifies Ttc21b-dependent microcephaly.
Region function
The CA1 pyramidal layer is the main hippocampal output stage, combining CA3 Schaffer-collateral and direct entorhinal input to support place coding, episodic and spatial memory.
Published in this region
expression only Expression only. Lee et al. 2001, the cloning paper, mapped GPR63 mRNA to frontal cortex with lower levels in thalamus, caudate, hypothalamus and midbrain. Allen ISH (experiment 74277675) shows weak hippocampus-biased signal in the CA1/CA2 pyramidal layers (energy 0.44-1.07 vs 0.68 whole brain). No CA1 functional study exists.
Predicted function
Prediction: in CA1 pyramidal neurons GPR63 would act as a lipid-sensing GPCR tuning excitability, via Gi inhibition of cAMP and GIRK activation or via signalling on the neuronal primary cilium. Knockout or CA1 knockdown should leave basal transmission intact but shift the Schaffer-collateral LTP threshold and spatial memory consolidation, and S1P applied to slices should lose a GPR63-dependent Ca2+ or GIRK component.
Innovation
★★★★☆ 4/5 GPR63 is still a deorphanisation project with a handful of papers and no hippocampal physiology, yet it is a druggable GPCR in the best-studied memory circuit.
Tools
Gpr63 mutant mice from Snedeker et al. 2019, including strain polymorphisms affecting ciliary targeting; S1P and dioleoyl-phosphatidic acid as weak agonists; Allen ISH experiment 74277675. No selective antagonist, validated antibody or Cre driver known.
References

Direct evidence located at the region

Gpr63 Allen ISH at the CCF centroid of CA1sp

Allen ISH experiment 74277675, section image 74255088 (section 158): the section that contains the CCF centroid of Field CA1, pyramidal layer according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Look it up yourself: Allen Mouse Brain ISH for Gpr63Allen reference atlas: CA1sp (structure 407)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Gpr63" or by parcellation_substructure "CA1sp")All genes confined to CA1sp + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
CA1sp MERFISH region locator
Real single-cell MERFISH coordinates for the CA1sp (Field CA1, pyramidal layer) 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

Gpr63 regional expression profile

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

Spatial profile

CA1sp
0.423
CA2sp
0.408
CA1sr
0.273
CA1so
0.266
PF
0.265
MGd
0.258
PCN
0.255
CA2so
0.254
SGN
0.253
LGd-ip
0.245
PT
0.241
CP
0.24
PO
0.239
LGd-sh
0.237
VPMpc
0.236
RH
0.234
ACB
0.23
SMT
0.229
MD
0.224
CL
0.22

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.321
Top-region fraction
0.049
Filter status
PASS

Interpretation limits