Aqp6

Aquaporin-6 (AQP-6)

Spatial tier: RESTRICTED · Class: ION_CHANNEL · Top region: AD (Anterodorsal nucleus) · Positive regions: 20/554

47.8Discovery Score
40.1Targetability Score
CEvidence grade C
What this means: Aqp6: fine CCF profile is restricted toward AD (top regions: AD, CENT2, CENT3, SIM, UVU; 20 positive regions); direct spatial validation is still required.

Function in AD: evidence, prediction, innovation

Gene function
Aqp6 encodes aquaporin-6, an atypical water-channel family member. Rather than sitting in the plasma membrane it resides largely in intracellular vesicles and behaves as a low-pH- and mercury-gated anion channel with high nitrate permeability plus modest water permeability, best established in kidney collecting duct intercalated cells.
Region function
The anterodorsal thalamic nucleus is the core thalamic node of the head-direction system, relaying vestibular-derived directional signals to postsubiculum and entorhinal cortex for spatial orientation.
Published in this region
none No region-specific literature found. Brain aquaporin surveys report AQP1, AQP4 and AQP9 in cerebral microvessels and glia rather than AQP6 (Kobayashi et al. 2001), and mouse Aqp6 is characterised as predominantly renal with intracellular retention (Nagase et al. 2007; Yasui et al. 1999).
Predicted function
Prediction: if aquaporin-6 is expressed by AD neurons or glia, its most plausible role is vesicular anion and water flux affecting intracellular pH and vesicle osmotic balance, not bulk water transport, since AQP6 opens only on acidification. Knockout should leave gross behaviour normal but degrade head-direction tuning stability at high firing rates. Confirming protein expression comes first.
Innovation
★★★☆☆ 3/5 AQP6 in thalamus is unexplored, but brain expression appears minimal and no loss-of-function neural tool exists.
Tools
anti-AQP6 antibodies (Nagase et al. 2007); Hg2+ and low pH as activators; no Aqp6 Cre or conditional allele; AD access via anterior-thalamic Cre lines and AAV.
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 Aqp6Allen reference atlas: AD (structure 64)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Aqp6" or by parcellation_substructure "AD")All genes confined to AD + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
AD MERFISH region locator
Real single-cell MERFISH coordinates for the AD (Anterodorsal 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.

Regional expression figure

Aqp6 regional expression profile

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

Spatial profile

AD
1.25
CENT2
0.7
CENT3
0.679
SIM
0.667
UVU
0.655
ANcr1
0.63
CUL4, 5
0.629
PFL
0.601
PYR
0.597
ANcr2
0.577
PRM
0.575
FOTU
0.572
NOD
0.555
DEC
0.537
LING
0.496
COPY
0.468
MH
0.442
AP
0.428
FL
0.418
DCO
0.35

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.352
Top-region fraction
0.072
Filter status
PASS

Interpretation limits