Ano1

Anoctamin-1 (Transmembrane protein 16A)

Spatial tier: STRICT_EXCLUSIVE · Class: ION_CHANNEL · Top region: MH (Medial habenula) · Positive regions: 5/554

48.2Discovery Score

46.4Targetability Score

CEvidence grade C

What this means: Ano1: predicted fine-region profile is strict-exclusive, with 5 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in MH: evidence, prediction, innovation

Gene function

Ano1 encodes TMEM16A, a calcium-activated chloride channel of the anoctamin family. Rising intracellular Ca2+ opens the pore and Cl- moves down its electrochemical gradient, which drives secretion in epithelia and shapes membrane potential, afterpotentials and firing rate in excitable cells. It is a classic target in airway epithelium, interstitial cells of Cajal and nociceptors.

Region function

The medial habenula is an epithalamic relay whose cholinergic/substance P neurons project almost exclusively through the fasciculus retroflexus to the interpeduncular nucleus. This MHb-IPN axis sets nicotine aversion and withdrawal, fear memory expression, anxiety and negative affect.

Published in this region

direct Cho et al. 2020 (EMBO Rep) used RNAscope, immunohistochemistry and slice recording to show that TMEM16A expression in the mouse brain is essentially restricted to the medial habenula; conditional ablation in ChAT+ mHb neurons flattened the afterhyperpolarization slope of spontaneous action potentials and produced anxiety-related behaviour. Song et al. 2022 (Behav Brain Res) found anhedonia-like behaviour after the same ChAT-restricted deletion, and Kim et al. 2026 (Mol Brain) reported early-onset schizophrenia-like phenotypes in mHb TMEM16A conditional knockouts.

Predicted function

Prediction: TMEM16A is the Ca2+-dependent chloride brake that stabilises the tonic pacemaking of ventral MHb cholinergic neurons, converting Ca2+ entry during each spike into a repolarising Cl- current. Removing it should raise MHb firing rate and ACh/glutamate output onto the IPN; pharmacological block (Ani9, T16Ainh-A01) should mimic the anxiety and anhedonia phenotypes, whereas potentiating TMEM16A should blunt nicotine withdrawal-induced MHb hyperactivity.

Innovation

★★☆☆☆ 2/5 Three published studies already manipulate TMEM16A specifically in MHb cholinergic neurons, so the region-gene pair is established rather than novel.

Tools

ChAT-IRES-Cre driver (JAX 006410 / 031661) crossed to floxed Ano1 alleles, as used by Cho 2020 and Song 2022; selective blockers Ani9, T16Ainh-A01 and CaCCinh-A01; activator Eact; commercial TMEM16A antibodies and validated RNAscope probes.

References

Direct evidence located at the region

Ano1 Allen ISH at the CCF centroid of MH

Allen ISH experiment 1472, section image 101362029 (section 231): the section that contains the CCF centroid of Medial habenula 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 Ano1 Allen reference atlas: MH (structure 483)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Ano1" or by parcellation_substructure "MH")All genes confined to MH + 3-D brain

Direct spatial evidence

MH MERFISH region locator — Real single-cell MERFISH coordinates for the MH (Medial habenula) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Allen ISH experiment 1472, image 101362041 -- target region: MH (Medial habenula)

Allen ISH experiment 1472, image 101362047 -- target region: MH (Medial habenula)

Regional expression figure

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

Spatial profile

7.05

4.85

LSc

3.97

LSr

3.42

LSv

2.04

ADP

1.56

MEPO

1.45

TRS

1.38

AVPV

1.2

SFO

1.15

1.06

AVP

0.994

SUM

0.924

VLPO

0.917

0.899

SCO

0.872

NDB

0.871

0.867

Evidence and specificity

Evidence status: PREDICTED_FINE
Direct sources: None; predicted localization only
Exclusive threshold: 12 positive regions out of 554
Spatial specificity: 0.401
Top-region fraction: 0.149
Filter status: PASS

Interpretation limits

Cell-type-to-region projection is imputed expression, not direct spatial measurement.
Adult reference atlases do not establish stability across age, sex, strain, state, or disease.
Transcript abundance does not guarantee protein abundance or genetic-tool performance.