Oxgr1

2-oxoglutarate receptor 1 (Alpha-ketoglutarate receptor 1) (G protein-coupled receptor 99)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: PVpo (Periventricular hypothalamic nucleus, preoptic part) · Positive regions: 30/554

43.9Discovery Score
33.9Targetability Score
CEvidence grade C
What this means: Oxgr1: fine CCF profile is region-biased toward PVpo (top regions: PVpo, PVi, SPA, PRC, SPFm); this is a discovery lead, not direct proof.

Function in PVpo: evidence, prediction, innovation

Gene function
OXGR1 (GPR99) is a Gq-coupled G protein-coupled receptor activated by the TCA-cycle intermediate 2-oxoglutarate (alpha-ketoglutarate) and by the inflammatory lipid leukotriene E4, which is why it is also called CysLT3. Activation raises intracellular calcium; the receptor is best characterised in kidney, where it couples metabolic state to acid-base and salt handling, and in airway epithelium.
Region function
The preoptic part of the periventricular hypothalamic nucleus is a thin periventricular cell group containing neuroendocrine and sleep-related neurons; it contributes to hypophysiotropic control (somatostatin, GHRH, dopamine) and to preoptic regulation of sleep and body temperature.
Published in this region
inferred No region-specific literature found. The closest evidence is that OXGR1 is a genuine neural receptor elsewhere: Cherif 2018 showed GPR91 and GPR99 signalling promotes retinal axon growth, and Diehl 2016 mapped GPR99 protein across murine organs including neural tissue, while structural work (Liu 2025) confirms its dual metabolite/leukotriene pharmacology.
Predicted function
Prediction: in the periventricular preoptic nucleus, which sits next to the third ventricle and samples CSF, OXGR1 would let neurons read extracellular alpha-ketoglutarate as a direct metabolic signal and depolarise through Gq, linking systemic energy or acid-base state to neuroendocrine and thermoregulatory output. Intracerebroventricular alpha-ketoglutarate should activate these neurons and shift GH/somatostatin release or body temperature, and Oxgr1 knockout is predicted to blunt metabolic-challenge-evoked changes in preoptic activity and thermoregulatory responses to fasting.
Innovation
★★★★★ 5/5 A metabolite-sensing GPCR positioned on the CSF-facing preoptic wall is an obvious but wholly untested route for direct metabolic sensing by neuroendocrine neurons.
Tools
Oxgr1 knockout mice; alpha-ketoglutarate and LTE4 as agonists; montelukast-insensitive CysLT3 pharmacology plus newly reported OXGR1-selective ligands; anti-OXGR1 antibodies; periventricular targeting via Sst-Cre or Ghrh-Cre crosses.
References

Direct evidence located at the region

Oxgr1 Allen ISH at the CCF centroid of PVpo

Allen ISH experiment 69860841, section image 69886093 (section 157): the section that contains the CCF centroid of Periventricular hypothalamic nucleus, preoptic 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 Oxgr1Allen reference atlas: PVpo (structure 133)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Oxgr1" or by parcellation_substructure "PVpo")All genes confined to PVpo + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
PVpo MERFISH region locator
Real single-cell MERFISH coordinates for the PVpo (Periventricular hypothalamic nucleus, preoptic 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

Oxgr1 regional expression profile

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

Spatial profile

PVpo
0.167
PVi
0.151
SPA
0.121
PRC
0.107
SPFm
0.106
SCO
0.0968
Su3
0.0943
PSTN
0.092
PMv
0.0879
PVa
0.0836
VMH
0.0731
DMH
0.0708
PH
0.0706
B
0.0683
PVT
0.0643
PVHd
0.0639
MPN
0.0633
OV
0.0616
ACB
0.0614
CP
0.0613

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
0.051
Filter status
PASS

Interpretation limits