Adora2b

Adenosine receptor A2b

Spatial tier: REGION_BIASED · Class: GPCR · Top region: SCO (Subcommissural organ) · Positive regions: 35/554

43.9Discovery Score
35.9Targetability Score
CEvidence grade C
What this means: Adora2b: fine CCF profile is region-biased toward SCO (top regions: SCO, SNr, VII, PVpo, III); this is a discovery lead, not direct proof.

Function in SCO: evidence, prediction, innovation

Gene function
ADORA2B is the low-affinity A2B adenosine receptor, a Gs- (and Gq-) coupled GPCR that raises cAMP only when extracellular adenosine rises well above baseline, as during hypoxia, inflammation or high metabolic demand. It is a classic hypoxia-inducible, HIF-regulated receptor in epithelium, endothelium and immune cells.
Region function
The subcommissural organ is an ependymal secretory gland in the roof of the third ventricle at the posterior commissure; it secretes SCO-spondin into cerebrospinal fluid to form Reissner's fibre, which contributes to CSF flow, aqueduct patency and axial/neurodevelopmental signalling.
Published in this region
none No region-specific literature found. In brain, ADORA2B has been studied in hippocampus, where Gile 2020 linked hippocampal ADORA2B and PER2 to midazolam-induced cognitive dysfunction, and in oligodendrocyte biology (Cherchi 2026); nothing addresses the subcommissural organ or its secretory ependyma.
Predicted function
Prediction: the subcommissural organ is a secretory epithelium bathed in CSF, exactly the setting where A2B receptors normally couple extracellular adenosine to cAMP-driven secretion and barrier function. A2B activation would therefore be expected to stimulate SCO-spondin release and Reissner's fibre formation when CSF adenosine rises (hypoxia, sleep pressure, high metabolic load). Adora2b knockout or the antagonist PSB-603 should reduce SCO secretory output and, over development, could produce aqueduct stenosis/hydrocephalus-like phenotypes; an A2B agonist (BAY 60-6583) should increase secretion.
Innovation
★★★★★ 5/5 Purinergic control of subcommissural organ secretion is entirely unstudied despite an obvious CSF-adenosine sensing role and existing selective drugs.
Tools
Adora2b knockout and floxed mice; agonist BAY 60-6583, antagonists PSB-603 and MRS1754; anti-A2B antibodies; SCO/ependymal targeting via FoxJ1-CreER and intracerebroventricular AAV.
References

Direct evidence located at the region

Adora2b Allen ISH at the CCF centroid of SCO

Allen ISH experiment 69855773, section image 69882909 (section 150): the section that contains the CCF centroid of Subcommissural organ 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 Adora2bAllen reference atlas: SCO (structure 599626923)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Adora2b" or by parcellation_substructure "SCO")All genes confined to SCO + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
SCO MERFISH region locator
Real single-cell MERFISH coordinates for the SCO (Subcommissural organ) 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

Adora2b regional expression profile

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

Spatial profile

SCO
0.858
SNr
0.636
VII
0.579
PVpo
0.574
III
0.558
LM
0.545
AD
0.542
SG
0.536
MT
0.535
LA
0.522
AIp1
0.521
PVi
0.516
VISC1
0.505
V
0.501
RPF
0.493
ME
0.487
LT
0.485
AId1
0.484
TEa1
0.483
NLOT1
0.48

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.271
Top-region fraction
0.049
Filter status
PASS

Interpretation limits