Gpr20

G protein-coupled receptor 20

Spatial tier: REGION_BIASED · Class: GPCR · Top region: MMd (Medial mammillary nucleus, dorsal part) · Positive regions: 29/554

46.9Discovery Score
35.0Targetability Score
CEvidence grade C
What this means: Gpr20: fine CCF profile is region-biased toward MMd (top regions: MMd, CLI, IG, AMBd, SSp-m1); this is a discovery lead, not direct proof.

Function in MMd: evidence, prediction, innovation

Gene function
GPR20 is an orphan class A G protein-coupled receptor most closely related to the opioid/somatostatin receptor cluster. It couples constitutively to Gi/o, lowering cAMP without any identified ligand, and is best known clinically as a surface antigen of gastrointestinal stromal tumours and interstitial cells of Cajal.
Region function
The medial mammillary nucleus is the hypothalamic node of the Papez/extended hippocampal circuit: it receives subicular input via the fornix and projects through the mammillothalamic tract to the anterior thalamic nuclei, supporting theta-paced spatial and episodic memory.
Published in this region
none No region-specific literature found. The only CNS data are from the original cloning paper: O'Dowd 1997 detected GPR20 transcripts by Northern blot in several human brain regions (and liver), with no nucleus-level resolution.
Predicted function
Prediction: as a constitutively active Gi-coupled receptor, GPR20 in dorsal medial mammillary neurons would set a tonic brake on adenylyl cyclase and therefore on HCN/Ih and cAMP-dependent burst firing, biasing these cells towards regular theta-locked discharge. Knockdown or a Gi-DREADD comparison should raise baseline cAMP and firing rate in mammillary neurons; behaviourally this predicts altered mammillothalamic theta coupling and mild spatial-memory changes. Deorphanisation in this nucleus is itself the first experiment.
Innovation
★★★★★ 5/5 A completely unstudied orphan receptor in a classic but molecularly under-characterised memory nucleus.
Tools
No selective ligand exists; anti-GPR20 antibodies and the GPR20-directed antibody-drug conjugate DS-6157a provide binding reagents; conditional knockdown via AAV-shRNA or CRISPR in Foxb1-Cre mice.
References

Direct evidence located at the region

Gpr20 Allen ISH at the CCF centroid of MMd

Allen ISH experiment 69857606, section image 69888485 (section 150): the section that contains the CCF centroid of Medial mammillary nucleus, dorsal part 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 Gpr20Allen reference atlas: MMd (structure 606826659)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Gpr20" or by parcellation_substructure "MMd")All genes confined to MMd + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
MMd MERFISH region locator
Real single-cell MERFISH coordinates for the MMd (Medial mammillary nucleus, dorsal part) 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

Gpr20 regional expression profile

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

Spatial profile

MMd
0.353
CLI
0.255
IG
0.229
AMBd
0.226
SSp-m1
0.192
MT
0.188
LC
0.188
ND
0.144
AAA
0.142
AUDd1
0.136
SSp-n1
0.135
IF
0.134
RO
0.126
RPA
0.126
VISam1
0.123
IPL
0.12
SSs1
0.115
SSp-bfd1
0.114
ORBvl1
0.11
NLOT3
0.109

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.282
Top-region fraction
0.053
Filter status
PASS

Interpretation limits