Best3

Bestrophin-3 (Vitelliform macular dystrophy 2-like protein 3)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: DG-po (Dentate gyrus, polymorph layer) · Positive regions: 37/554

45.1Discovery Score
38.3Targetability Score
CEvidence grade C
What this means: Best3: fine CCF profile is region-biased toward DG-po (top regions: DG-po, IPR, AV, DG-sg, PSV); this is a discovery lead, not direct proof.

Function in DG-po: evidence, prediction, innovation

Gene function
Best3 encodes bestrophin-3, a calcium-activated anion channel of the bestrophin family. Bestrophins are pentamers with a single central pore gated by intracellular calcium; in vascular smooth muscle bestrophin-3 carries the cGMP-dependent calcium-activated chloride current. The related Best1 is an established glutamate- and GABA-permeable astrocyte channel, so bestrophins can mediate gliotransmitter efflux as well as chloride flux.
Region function
The polymorph layer (hilus) of the dentate gyrus contains glutamatergic mossy cells and GABAergic interneurons forming the feedback loop that controls granule-cell excitability, pattern separation and seizure threshold.
Published in this region
none No region-specific literature found. The closest brain finding is Golubinskaya et al. 2019 (Front Physiol), who detected bestrophin-3 protein and splice variants in a nestin-positive astrocyte subpopulation of neonatal mouse brain after hypoxia-ischaemia and linked its induction to ER stress; there is no Allen mouse ISH dataset for Best3 and no hippocampal study of any kind.
Predicted function
Prediction: if bestrophin-3 is present in hilar astrocytes or mossy cells it would most plausibly provide a calcium-activated chloride or glutamate/GABA-permeable conductance stabilising membrane potential and contributing to tonic inhibition of granule cells, by analogy with Best1 in hippocampal astrocytes. Hilar Best3 deletion is predicted to reduce tonic GABA current, lower seizure threshold and degrade pattern separation.
Innovation
★★★★★ 5/5 Bestrophin-3 has never been studied in hippocampus, yet the hilus is a seizure-critical microcircuit with mature Cre and AAV tools.
Tools
Best3 knockdown reagents and anti-bestrophin-3 antibodies from the vascular field (Matchkov 2008; Golubinskaya 2019); non-selective bestrophin blockers NPPB and niflumic acid; hilar access via Drd2-Cre or Calcr-Cre mossy-cell lines and GFAP/Aldh1l1 astrocyte drivers.
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 Best3Allen reference atlas: DG-po (structure 10704)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Best3" or by parcellation_substructure "DG-po")All genes confined to DG-po + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
DG-po MERFISH region locator
Real single-cell MERFISH coordinates for the DG-po (Dentate gyrus, polymorph layer) 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

Best3 regional expression profile

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

Spatial profile

DG-po
0.838
IPR
0.756
AV
0.711
DG-sg
0.604
PSV
0.54
CA3slm
0.539
VPM
0.507
LGd-ip
0.412
LD
0.384
PVH
0.375
IPC
0.37
VPL
0.366
PO
0.365
SCO
0.348
VAL
0.348
LGd-co
0.343
CA3sr
0.321
SMT
0.314
LGd-sh
0.303
PCN
0.301

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.319
Top-region fraction
0.050
Filter status
PASS

Interpretation limits