| Claim/Observation | Biological level (molecular/cellular/organism) | Evidence type (genetics, imaging, electrophysiology, biochemistry, review) | Key details (include quantitative where available) | Source (authors, year) | DOI/URL | Citation ID |
|---|---|---|---|---|---|---|
| Zebrafish **tomt** is the gene disrupted in the classic **mercury/mrc** mutant and is orthologous to human **LRTOMT/TOMT (DFNB63)** | Molecular/organism | Genetics | mercury alleles are nonsense mutations predicted to truncate Tomt before or within the putative O-methyltransferase domain; links zebrafish locus to human deafness gene ortholog | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000000, pqac-00000001) |
| Tomt is essential for hair-cell mechanotransduction; tomt mutants have auditory/vestibular dysfunction | Cellular/organism | Genetics, electrophysiology | tomt-deficient hair cells lack mechanotransduction (MET); mutants show auditory and vestibular phenotypes consistent with loss of sensory hair-cell function | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000000, pqac-00000006, pqac-00000012) |
| Tomt localizes to the secretory pathway rather than the hair bundle | Cellular | Imaging | GFP-tagged Tomt is enriched in the Golgi and excluded from stereociliary bundles; partial co-localization shown with medial Golgi marker Mgat1a_1–110-mKate2 | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000000, pqac-00000002, pqac-00000006, pqac-00000015) |
| Loss of Tomt selectively disrupts Tmc trafficking to the hair bundle | Cellular | Imaging, genetics | In tomt/mercury mutants, **Tmc1-GFP** and **Tmc2b-GFP** are absent from bundles and remain in the cell body, while other MET-complex proteins can still localize to bundles | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000000, pqac-00000001, pqac-00000004, pqac-00000016, pqac-00000017) |
| Tomt acts cell-autonomously and can restore Tmc localization/MET when re-expressed | Cellular | Genetics, imaging, functional rescue | Mosaic Tomt expression restores Tmc2b-GFP bundle localization; hair-cell-specific Tomt-GFP rescues FM dye uptake and MET activity in mutants | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000003, pqac-00000004) |
| Tomt is required not only during development but also in mature hair cells | Cellular | Genetics, functional rescue | Heat-shock induction of Tomt-GFP restored previously silent mutant hair cells within **~4 h**, indicating an ongoing role in maintaining/assembling MET function | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000002, pqac-00000003) |
| Tomt-deficient hair cells lack MET currents despite otherwise recognizable hair-cell ionic properties | Cellular | Electrophysiology | mercury/tomt mutant hair cells show no detectable evoked MET currents and loss of FM 1–43/FM 4–64 uptake, but retain normal K+ currents and intact inward Ca2+ current used to verify cell identity | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000006, pqac-00000005) |
| Mouse TOMT can substitute for zebrafish Tomt, but COMT cannot | Molecular/cellular | Genetics, rescue | Mouse TOMT-GFP restores mechanotransduction/FM dye uptake in mercury mutants, whereas zebrafish Comta-GFP does not rescue, arguing against a simple catecholamine-metabolism explanation | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000001, pqac-00000002, pqac-00000007) |
| TOMT physically interacts with TMC1 | Molecular | Biochemistry | HEK293 co-immunoprecipitation supports direct TOMT–TMC1 interaction; supports a trafficking/chaperone-like role in the secretory pathway | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000000, pqac-00000004, pqac-00000005) |
| The putative catalytic histidine is not strictly required for Tomt-mediated rescue | Molecular/cellular | Mutagenesis, functional rescue, biochemistry | **H183A** in TOMT enhanced TOMT–TMC1 interaction in co-IP and did not abolish rescue in zebrafish assays; suggests canonical COMT-like active-site chemistry is not essential for hair-cell function | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000002, pqac-00000005, pqac-00000007, pqac-00000008, pqac-00000011) |
| The enzymatic domain is functionally important, but the physiological substrate remains unknown | Molecular | Structure-function, biochemistry | Predicted SAM-dependent methyltransferase domain is required for rescue in truncation tests, yet no in vivo substrate is identified; only modest in vitro catechol O-methyltransferase activity toward norepinephrine reported, so true substrate specificity remains unresolved | Erickson et al., 2017 | https://doi.org/10.17863/cam.24577 | (pqac-00000001, pqac-00000003, pqac-00000007, pqac-00000011, pqac-00000012) |
| Recent expert reviews frame TOMT primarily as a TMC trafficking factor in MET biology | Molecular/cellular | Review | 2023 review states TOMT/LRTOMT mutations cause DFNB63, places TOMT in ER/secretory-pathway trafficking of TMC1 into stereocilia, and treats TOMT as affecting MET indirectly rather than as a pore-forming channel component | Jung & Müller, 2023 | https://doi.org/10.1016/j.cophys.2023.100632 | (pqac-00000010, pqac-00000013, pqac-00000014) |


*Table: This table compiles the core evidence linking zebrafish tomt/Tomt to hair-cell mechanotransduction, emphasizing gene identity, localization, Tmc trafficking, rescue experiments, and the unresolved question of catalytic methyltransferase activity.*