Otop1

Proton channel OTOP1 (Otopetrin-1)

Spatial tier: STRICT_EXCLUSIVE · Class: ION_CHANNEL · Top region: RT (Reticular nucleus of the thalamus) · Positive regions: 4/554

49.9Discovery Score
41.0Targetability Score
CEvidence grade C
What this means: Otop1: predicted fine-region profile is strict-exclusive, with 4 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in RT: evidence, prediction, innovation

Gene function
Otop1 encodes otopetrin-1, founder of a proton-selective ion channel family: H+ influx in acid, efflux in alkali, blocked by Zn2+. It transduces sour taste in type III taste cells and the taste of ammonium chloride, and is required for otoconia formation, tilted/mergulhador mutants lacking otoconia and being vestibular-deficient.
Region function
The reticular thalamic nucleus is the GABAergic gate around dorsal thalamus, source of sleep spindles and state-dependent filtering of thalamocortical traffic.
Published in this region
inferred No region-specific literature found. PubMed queries for Otop1 in brain return only taste, otolith and heterologous-expression studies, the closest central link being the sour-taste pathway from Otop1-positive type III taste cells to brainstem relays (Zhang et al. 2019), with no Otop1 reported in thalamus.
Predicted function
Prediction: in RT neurons Otop1 would be a pH-gated proton conductance reading acidification, which in thalamus swings with burst firing, spindles and sleep hypercapnia. Loss should slow pH recovery after burst trains and alter T-type-dependent burst duration, seen as changed spindle frequency or duration and altered arousal from hypercapnic challenge.
Innovation
★★★★★ 5/5 Otop1 is studied only in taste buds and otoconia, so a thalamic proton channel would link brain pH to sleep rhythms.
Tools
Otop1 tilted (tlt) and mergulhador mutants and knockout mice; Zn2+ as acute blocker; structure-guided small-molecule OTOP1 inhibitors; heterologous proton-current assays. RT cells are targeted with Pvalb-Cre, Sst-Cre and Vgat-Cre.
References

Direct evidence located at the region

Otop1 Allen ISH at the CCF centroid of RT

Allen ISH experiment 71210583, section image 70939175 (section 158): the section that contains the CCF centroid of Reticular nucleus of the thalamus 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
RT MERFISH region locator
Real single-cell MERFISH coordinates for the RT (Reticular nucleus of the thalamus) 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 71210583, image 70939129 -- target region: RT (Reticular nucleus of the thalamus)
Allen ISH experiment 71210583, image 70939129 -- target region: RT (Reticular nucleus of the thalamus)
DIRECT ALLEN ISH
Allen ISH experiment 71210583, image 70939131 -- target region: RT (Reticular nucleus of the thalamus)
Allen ISH experiment 71210583, image 70939131 -- target region: RT (Reticular nucleus of the thalamus)

Regional expression figure

Otop1 regional expression profile

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

Spatial profile

RT
0.254
PBG
0.118
AOBgr
0.11
AP
0.0871
PVHd
0.0451
MH
0.0408
DR
0.0399
NTS
0.0396
MOBopl
0.0367
EW
0.0356
RL
0.0349
AOBmi
0.0332
MOBipl
0.0294
CA1sp
0.0288
B
0.0255
SAG
0.0255
MOBmi
0.0236
CA2sp
0.0218
TTd
0.0209
TTv
0.0209

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.427
Top-region fraction
0.206
Filter status
PASS

Interpretation limits