Adgrg5

Adhesion G protein-coupled receptor G5 (G protein-coupled receptor 114) (G protein-coupled receptor PGR27) [Cleaved into: Adhesion G protein-coupled receptor G5, N-terminal fragment (ADGRG5 N-terminal

Spatial tier: RESTRICTED · Class: GPCR · Top region: PO (Posterior complex of the thalamus) · Positive regions: 20/554

53.2Discovery Score
40.8Targetability Score
CEvidence grade C
What this means: Adgrg5: fine CCF profile is restricted toward PO (top regions: PO, Eth, MGv, MGd, SMT; 20 positive regions); direct spatial validation is still required.

Function in PO: evidence, prediction, innovation

Gene function
Adgrg5 encodes GPR114/ADGRG5, an adhesion G protein-coupled receptor. Its long extracellular region ends in a GAIN domain that self-cleaves, exposing a tethered peptide agonist (the Stachel sequence) which folds back into the seven-transmembrane core to activate Gs and raise cAMP. Cleavage is required for activation, and the receptor shows high constitutive and mechanically sensitive activity.
Region function
The posterior complex of the thalamus (PO) is a higher-order thalamic nucleus carrying whisker-touch, self-motion and nociceptive signals, relaying between brainstem, cortical layer 5 and secondary somatosensory/motor cortex rather than acting as a simple first-order relay.
Published in this region
none No region-specific literature found. Published ADGRG5 work is entirely biochemical and immunological - tethered-agonist activation and cleavage dependence (Bernadyn et al. 2023; Wilde et al. 2016), cryo-EM of Stachel-bound ADGRG receptors (Ping et al. 2022), and expression restricted to eosinophils, lymphocytes, monocytes and dendritic cells (Hamann et al. 2015). No study reports ADGRG5 in brain, thalamus or neurons.
Predicted function
Prediction: if the PO signal is genuinely neuronal rather than from perivascular or thalamic immune cells, ADGRG5 would most plausibly act as a constitutively active, mechanically tuned Gs/cAMP source in higher-order thalamocortical relay neurons, setting resting cAMP tone and thereby HCN-dependent burst-versus-tonic firing mode and the gain of layer-5 driver input. Knockout or Stachel blockade would then shift PO neurons toward burst firing and degrade whisker-touch and nociceptive transmission to secondary somatosensory cortex. The required first experiment is RNAscope plus a cell-type check to confirm neuronal expression.
Innovation
★★★★★ 5/5 The receptor has never been reported in brain at all, so any validated neuronal role in a higher-order thalamic nucleus would be entirely new.
Tools
No Cre/Flp driver, validated antibody or characterised brain knockout reported. Available chemistry only: dihydromunduletone (ADGRG1/ADGRG5 antagonist), gedunin- and khivorin-derived partial agonists, and synthetic Stachel peptide agonists. Detection currently requires RNAscope or a knock-in epitope tag; PO itself is accessible by standard thalamic AAV targeting.
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 Adgrg5Allen reference atlas: PO (structure 1020)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Adgrg5" or by parcellation_substructure "PO")All genes confined to PO + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
PO MERFISH region locator
Real single-cell MERFISH coordinates for the PO (Posterior complex of the thalamus) 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

Adgrg5 regional expression profile

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

Spatial profile

PO
0.449
Eth
0.299
MGv
0.269
MGd
0.254
SMT
0.212
MGm
0.211
VPLpc
0.204
CL
0.173
VPL
0.173
VPM
0.164
LP
0.162
PCN
0.161
VPMpc
0.16
SGN
0.152
LGd-ip
0.134
VAL
0.127
LGd-sh
0.125
LGd-co
0.119
VM
0.114
MD
0.101

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.447
Top-region fraction
0.098
Filter status
PASS

Interpretation limits