Adgrf4

Adhesion G protein-coupled receptor F4 (G protein-coupled receptor 115)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: AV (Anteroventral nucleus of thalamus) · Positive regions: 33/554

42.7Discovery Score
38.0Targetability Score
CEvidence grade C
What this means: Adgrf4: fine CCF profile is region-biased toward AV (top regions: AV, AMd, IAD, PCN, VAL); this is a discovery lead, not direct proof.

Function in AV: evidence, prediction, innovation

Gene function
ADGRF4 (GPR115) is an adhesion GPCR: a seven-transmembrane receptor with a long extracellular region cleaved at a GAIN/GPS domain, so that a tethered Stachel peptide activates the receptor when the N-terminal fragment is shed under mechanical or ligand stress. Its known biology is epithelial: Chiba et al. 2020 showed it is required for enamel mineralisation via Car6, and Winkler et al. 2022 showed it drives keratinocyte stratification along KRT1 filaments.
Region function
The anteroventral thalamic nucleus relays mammillary body and subicular signals to retrosplenial and cingulate cortex within the extended hippocampal circuit, and carries a large head-direction cell population supporting spatial orientation.
Published in this region
none No region-specific literature found. The closest data are the IMPC Adgrf4 knockout (MGI:1925499), which reports only an eye/vision phenotype and no adult brain expression, and the absence of any Adgrf4 ISH experiment in the Allen Mouse Brain Atlas.
Predicted function
Prediction: as a mechanically gated adhesion GPCR, ADGRF4 in AV would most plausibly act at adhesive contacts between relay neurons and mammillothalamic or retrosplenial afferents, or during thalamocortical wiring, coupling contact force to Gq/G12-13 signalling. AV-restricted deletion should spare gross anatomy but degrade head-direction cell tuning and allocentric tasks. A Stachel agonist peptide plus AAV-Cre in floxed mice is a feasible first test.
Innovation
★★★★★ 5/5 An epithelial adhesion GPCR with zero CNS literature, paired with a head-direction circuit that has well-defined physiological readouts.
Tools
IMPC/KOMP Adgrf4 knockout and conditional-ready alleles (MGI:1925499); GPR115 antibodies validated in skin (Winkler 2022); generic adhesion-GPCR Stachel agonist peptides. No Cre driver or small-molecule ligand known.
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 Adgrf4Allen reference atlas: AV (structure 255)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Adgrf4" or by parcellation_substructure "AV")All genes confined to AV + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
AV MERFISH region locator
Real single-cell MERFISH coordinates for the AV (Anteroventral nucleus of 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

Adgrf4 regional expression profile

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

Spatial profile

AV
1.1
AMd
0.798
IAD
0.764
PCN
0.733
VAL
0.678
SSp-tr4
0.556
SSp-ll4
0.543
CL
0.536
SSp-bfd4
0.52
AMv
0.513
SSp-ul4
0.503
CM
0.497
SSp-n4
0.496
VISp4
0.492
SSp-m4
0.487
SSp-un4
0.482
VISa4
0.469
LD
0.463
VISrl4
0.442
LGd-ip
0.441

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.297
Top-region fraction
0.055
Filter status
PASS

Interpretation limits