Asic5

Bile acid-sensitive ion channel (BASIC) (Acid-sensing ion channel subunit family member 5) (Amiloride-sensitive cation channel 5) (Brain-liver-intestine amiloride-sensitive Na(+) channel) (BLINaC)

Spatial tier: STRICT_EXCLUSIVE · Class: ION_CHANNEL · Top region: DCO (Dorsal cochlear nucleus) · Positive regions: 4/554

51.2Discovery Score
39.0Targetability Score
CEvidence grade C
What this means: Asic5: predicted fine-region profile is strict-exclusive, with 4 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in DCO: evidence, prediction, innovation

Gene function
ASIC5 (also called BLINaC or BASIC) is the most divergent member of the DEG/ENaC acid-sensing ion channel family. Unlike other ASICs it is barely activated by protons; it carries a constitutive Na+-permeable leak current that is gated by bile acids and by changes in membrane mechanics or lipid environment. In neurons such a standing cation conductance sets resting potential and intrinsic excitability.
Region function
The dorsal cochlear nucleus is a cerebellum-like auditory structure that combines primary auditory-nerve input with multimodal somatosensory and vestibular input via a granule-cell parallel fibre system, supporting spectral cue processing for sound localisation and implicated in tinnitus.
Published in this region
expression only Boiko et al. 2014 (PLoS One) mapped Asic5 with a lacZ reporter and found expression essentially restricted in brain to vestibulocerebellar unipolar brush cells plus staining in the dorsal cochlear nucleus, without further characterising the DCO cells. Kreko-Pierce et al. 2020 (Sci Rep) showed Asic5 knockout reduces the intrinsic excitability of type II (mGluR1alpha+, calretinin-negative) unipolar brush cells and causes ataxia, and note that type II UBCs reside chiefly in the vestibulocerebellum and dorsal cochlear nucleus. No DCO-specific physiology has been published.
Predicted function
Prediction: ASIC5 provides a tonic depolarising Na+ leak in DCO unipolar brush cells, the intrinsic amplifier of the granule-cell/parallel-fibre input layer. Knockout should hyperpolarise these cells, reduce spontaneous firing and blunt the prolonged UBC response to mossy fibre glutamate, degrading multisensory gain control over fusiform cells. Behaviourally this predicts impaired sound-localisation and altered gap-detection/tinnitus-like phenotypes rather than deafness; chemogenetic silencing of Asic5+ DCO cells should reproduce the deficit.
Innovation
★★★★★ 5/5 Only a single passing sentence documents Asic5 in the DCO despite an existing knockout line and a well-defined UBC circuit.
Tools
Asic5 knockout / lacZ reporter mouse (Boiko 2014; Kreko-Pierce 2020); UBC subtype markers mGluR1alpha and calretinin; bile acids as activators and the DEG/ENaC blockers amiloride and diminazene; Allen mouse ISH dataset 69236771. No Asic5-Cre line reported.
References

Direct evidence located at the region

Asic5 Allen ISH at the CCF centroid of DCO

Allen ISH experiment 69236771, section image 69084425 (section 112): the section that contains the CCF centroid of Dorsal cochlear nucleus 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

Direct spatial evidence

MERFISH REGION LOCATOR
DCO MERFISH region locator
Real single-cell MERFISH coordinates for the DCO (Dorsal cochlear nucleus) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 69236771, image 69084391 -- target region: DCO (Dorsal cochlear nucleus)
Allen ISH experiment 69236771, image 69084391 -- target region: DCO (Dorsal cochlear nucleus)
DIRECT ALLEN ISH
Allen ISH experiment 69236771, image 69084393 -- target region: DCO (Dorsal cochlear nucleus)
Allen ISH experiment 69236771, image 69084393 -- target region: DCO (Dorsal cochlear nucleus)

Regional expression figure

Asic5 regional expression profile

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

Spatial profile

DCO
0.145
MEPO
0.0884
DN
0.0643
AVPV
0.038
OV
0.0343
VCO
0.0304
NOD
0.0279
HATA
0.0268
SFO
0.0242
KF
0.0232
ME
0.0219
CA2slm
0.02
FL
0.0198
DG-mo
0.0192
AVP
0.0185
DR
0.0183
CA1slm
0.0174
CA2sr
0.017
DP
0.0164
LING
0.0163

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.408
Top-region fraction
0.174
Filter status
PASS

Interpretation limits