Abcc9

ATP-binding cassette sub-family C member 9 (Sulfonylurea receptor 2)

Spatial tier: RESTRICTED · Class: ION_CHANNEL · Top region: AP (Area postrema) · Positive regions: 15/554

45.9Discovery Score
36.9Targetability Score
CEvidence grade C
What this means: Abcc9: fine CCF profile is restricted toward AP (top regions: AP, LIN, PMv, MDRNd, PAS; 15 positive regions); direct spatial validation is still required.

Function in AP: evidence, prediction, innovation

Gene function
ABCC9 encodes SUR2, an ATP-binding-cassette protein with no transport function of its own that serves as the regulatory subunit of ATP-sensitive potassium (KATP) channels, co-assembling with Kir6.1 or Kir6.2 pore subunits. SUR2 reads the intracellular ATP/ADP ratio and thereby couples metabolic state to potassium conductance and excitability. It binds sulfonylureas such as glibenclamide and openers such as pinacidil; gain-of-function mutations cause Cantu syndrome and loss-of-function causes ABCC9-related intellectual disability myopathy syndrome.
Region function
The area postrema is a circumventricular organ on the floor of the fourth ventricle with fenestrated capillaries and no blood-brain barrier; it samples circulating toxins, hormones and peptides and drives nausea, conditioned taste avoidance and suppression of feeding through the NTS and parabrachial nucleus.
Published in this region
inferred No region-specific literature found. Thomzig et al. 2005 mapped Kir6.1 and Kir6.2 across rat brain and found Kir6.1 concentrated in glia and vasculature rather than neurons, and Nelson et al. 2015 report that brain SUR2 transcripts are largely pericytic, smooth-muscle and endothelial, which fits the exceptionally dense fenestrated vasculature of the area postrema.
Predicted function
Prediction: in the area postrema, SUR2-containing KATP channels most likely sit on mural and endothelial cells of the fenestrated plexus and on a subset of glucose-sensitive neurons, translating falling ATP during hypoglycaemia or toxin exposure into hyperpolarisation and altered local perfusion and permeability. Deleting Abcc9 in AP, or opening the channel with pinacidil, should blunt AP recruitment by circulating emetic agents and reduce lithium chloride- or GLP-1-agonist-induced conditioned taste avoidance; a Cantu gain-of-function knock-in should exaggerate that loss.
Innovation
★★★★☆ 4/5 KATP metabolic sensing is an obvious fit for a barrier-free chemosensory organ, yet no study has tested SUR2 in the area postrema although floxed and gain-of-function alleles exist.
Tools
Abcc9 floxed and SUR2-null mice; Cantu gain-of-function knock-ins (R1154Q, V65M); pinacidil and diazoxide openers, glibenclamide blocker, SUR2-selective inhibitors described by Li et al. 2024; anti-Kir6.1/SUR2 antibodies. AP cell types are accessible with Gfral-Cre, Calcr-Cre and Glp1r-Cre plus fourth-ventricle AAV.
References

Direct evidence located at the region

Abcc9 Allen ISH at the CCF centroid of AP

Allen ISH experiment 76003609, section image 76000981 (section 153): the section that contains the CCF centroid of Area postrema 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 Abcc9Allen reference atlas: AP (structure 207)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Abcc9" or by parcellation_substructure "AP")All genes confined to AP + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
AP MERFISH region locator
Real single-cell MERFISH coordinates for the AP (Area postrema) 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

Abcc9 regional expression profile

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

Spatial profile

AP
0.961
LIN
0.696
PMv
0.622
MDRNd
0.575
PAS
0.524
AV
0.518
AIp1
0.517
INC
0.51
ECT1
0.501
PGRNd
0.5
GU1
0.485
AUDpo1
0.469
III
0.467
ORBvl1
0.459
AId1
0.446
AUDv1
0.437
VII
0.435
IPR
0.43
PARN
0.429
RN
0.426

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.291
Top-region fraction
0.069
Filter status
PASS

Interpretation limits