Tmc5

Transmembrane channel-like protein 5

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: ARH (Arcuate hypothalamic nucleus) · Positive regions: 30/554

45.3Discovery Score
35.2Targetability Score
CEvidence grade C
What this means: Tmc5: fine CCF profile is region-biased toward ARH (top regions: ARH, PBG, IMD, CL, PO); this is a discovery lead, not direct proof.

Function in ARH: evidence, prediction, innovation

Gene function
TMC5 belongs to the transmembrane channel-like family, relatives of TMC1/TMC2 that form the hair-cell mechanotransduction channel. It is predicted to be a mechanosensitive cation channel or ion transporter at the plasma membrane. Its normal expression is largely epithelial (airway, gut, prostate) and it is repeatedly upregulated in prostate, gastric and liver cancer.
Region function
The arcuate nucleus sits at the base of the hypothalamus next to the median eminence, where AgRP/NPY and POMC neurons sense leptin, ghrelin and nutrients to set food intake and energy expenditure; its kisspeptin and dopaminergic neurons also gate GnRH pulses and prolactin.
Published in this region
none No region-specific literature found. The closest finding is Braz et al. 2026, where Tmc5 deletion in mouse sensory neurons reduced mechanical, heat and cold nociception and increased scratching, showing Tmc5 can shape neuronal sensory signalling; Allen ISH (experiment 69981067) gives only near-background arcuate signal (energy 0.03).
Predicted function
Prediction: if TMC5 protein is really present in ARH, the likeliest role is a mechano- or osmo-sensitive cation conductance in tanycytes or in neurons contacting the median eminence, tuning resting potential to ventricular osmolality and nutrient flux. Conditional knockout should alter fasting-refeeding dynamics and osmotically evoked firing rather than baseline weight. The prediction is speculative given weak atlas support.
Innovation
★★★★★ 5/5 No published work places Tmc5 in hypothalamus at all, so a confirmed arcuate role would be new, though low atlas signal is a real risk.
Tools
Tmc5 knockout mice used by Braz et al. 2026; TMC-family antibodies and TMC5 cancer-cell reagents; Allen ISH experiment 69981067. No Cre driver, agonist or blocker known.
References

Direct evidence located at the region

Tmc5 Allen ISH at the CCF centroid of ARH

Allen ISH experiment 69981067, section image 69892022 (section 152): the section that contains the CCF centroid of Arcuate hypothalamic 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
ARH MERFISH region locator
Real single-cell MERFISH coordinates for the ARH (Arcuate hypothalamic 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

Tmc5 regional expression profile

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

Spatial profile

ARH
0.245
PBG
0.177
IMD
0.158
CL
0.157
PO
0.15
PCN
0.15
Eth
0.149
ME
0.147
MD
0.139
CM
0.138
SMT
0.137
RH
0.132
PVpo
0.131
PVT
0.11
VPMpc
0.101
VAL
0.0988
PVa
0.0949
PVi
0.0921
SGN
0.0892
LP
0.0884

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.314
Top-region fraction
0.054
Filter status
PASS

Interpretation limits