{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the query requested a summary of the function of ZNF716, none of the provided abstracts mention or investigate ZNF716. Instead, the studies focus on transmembrane channel‐like proteins—primarily TMC1 and TMC2—and related components of the hair cell mechanotransduction complex. These investigations demonstrate that TMC1 and TMC2 are critical for converting mechanical stimuli into electrical signals in inner ear hair cells. Their expression, precise localization at stereocilia tips, and incorporation into mechanosensitive ion channels (often along with accessory proteins such as LHFPL5, TMIE, and CIB2) support a central role in forming the pore and modulating key channel properties including ionic conductance, calcium permeability, and adaptation mechanisms. Mutations in these proteins alter channel properties and are linked to hearing loss and balance defects, while gene augmentation studies provide evidence that exogenous TMC1 or TMC2 can restore mechanotransduction and partially rescue auditory function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies reinforce these findings by detailing the biophysical and structural features of TMC1, including its potential assembly as a dimer, its similarity to TMEM16 channels, and the impact of specific point mutations on channel function. They highlight that changes in TMC1-associated channel properties—such as reduced calcium permeability, diminished conductance, or altered resting open probability—can compromise hair cell function, ultimately leading to auditory and vestibular deficits. Importantly, while these comprehensive investigations elucidate multiple facets of the TMC-dependent mechanotransduction apparatus, no data in this set address any role for ZNF716. Thus, the function of ZNF716 remains undetermined within the context of these reports, and further research would be required to explore any potential involvement of ZNF716 in hair cell physiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stacy S Drury, Bronya J B Keats "}, {"type": "b", "children": [{"type": "t", "text": "Mouse tales from Kresge: the deafness mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Acad Audiol (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14552423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14552423"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carmen Martínez-Cué, Noemí Rueda, Eva García, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Behav Brain Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbr.2005.04.016"}], "href": "https://doi.org/10.1016/j.bbr.2005.04.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15941601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15941601"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valentina Labay, Rachel M Weichert, Tomoko Makishima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Topology of transmembrane channel-like gene 1 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi1004377"}], "href": "https://doi.org/10.1021/bi1004377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20672865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20672865"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yoshiyuki Kawashima, Gwenaëlle S G Géléoc, Kiyoto Kurima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI60405"}], "href": "https://doi.org/10.1172/JCI60405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22105175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22105175"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bifeng Pan, Gwenaelle S Géléoc, Yukako Asai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2013.06.019"}], "href": "https://doi.org/10.1016/j.neuron.2013.06.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23871232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23871232"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kyunghee X Kim, Maryline Beurg, Carole M Hackney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of transmembrane channel-like proteins in the operation of hair cell mechanotransducer channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1085/jgp.201311068"}], "href": "https://doi.org/10.1085/jgp.201311068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24127526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24127526"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Charles Askew, Cylia Rochat, Bifeng Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tmc gene therapy restores auditory function in deaf mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.aab1996"}], "href": "https://doi.org/10.1126/scitranslmed.aab1996"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26157030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26157030"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kiyoto Kurima, Seham Ebrahim, Bifeng Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.07.058"}], "href": "https://doi.org/10.1016/j.celrep.2015.07.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26321635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26321635"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Maryline Beurg, Adam C Goldring, Robert Fettiplace "}, {"type": "b", "children": [{"type": "t", "text": "The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Physiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1085/jgp.201511458"}], "href": "https://doi.org/10.1085/jgp.201511458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26324676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26324676"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Laura F Corns, Stuart L Johnson, Corné J Kros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2439-15.2016"}], "href": "https://doi.org/10.1523/JNEUROSCI.2439-15.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26758827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26758827"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Arnaud P J Giese, Yi-Quan Tang, Ghanshyam P Sinha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-00061-1"}], "href": "https://doi.org/10.1038/s41467-017-00061-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28663585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28663585"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Maryline Beurg, Runjia Cui, Adam C Goldring, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-04589-8"}], "href": "https://doi.org/10.1038/s41467-018-04589-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29872055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29872055"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Angela Ballesteros, Cristina Fenollar-Ferrer, Kenton Jon Swartz "}, {"type": "b", "children": [{"type": "t", "text": "Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.38433"}], "href": "https://doi.org/10.7554/eLife.38433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30063209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30063209"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hiroshi Nakanishi, Kiyoto Kurima, Bifeng Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tmc2 expression partially restores auditory function in a mouse model of DFNB7/B11 deafness caused by loss of Tmc1 function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-29709-8"}], "href": "https://doi.org/10.1038/s41598-018-29709-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30108230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30108230"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yukako Asai, Bifeng Pan, Carl Nist-Lund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-28958-x"}], "href": "https://doi.org/10.1038/s41598-018-28958-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30108254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30108254"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Bifeng Pan, Nurunisa Akyuz, Xiao-Ping Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMC1 Forms the Pore of Mechanosensory Transduction Channels in Vertebrate Inner Ear Hair Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2018.07.033"}], "href": "https://doi.org/10.1016/j.neuron.2018.07.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30138589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30138589"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Shanthini Mahendrasingam, David N Furness "}, {"type": "b", "children": [{"type": "t", "text": "Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-37563-x"}], "href": "https://doi.org/10.1038/s41598-018-37563-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30718571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30718571"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Adam C Goldring, Maryline Beurg, Robert Fettiplace "}, {"type": "b", "children": [{"type": "t", "text": "The contribution of TMC1 to adaptation of mechanoelectrical transduction channels in cochlear outer hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/JP278799"}], "href": "https://doi.org/10.1113/JP278799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31633194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31633194"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "D C Soler, M Manikandan, S R Gopal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An uncharacterized region within the N-terminus of mouse TMC1 precludes trafficking to plasma membrane in a heterologous cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-51336-0"}], "href": "https://doi.org/10.1038/s41598-019-51336-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31649296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31649296"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Soichiro Yamaguchi, Maho Hamamura, Ken-Ichi Otsuguro "}, {"type": "b", "children": [{"type": "t", "text": "A Mechanosensitive Channel, Mouse Transmembrane Channel-Like Protein 1 (Mtmc1) Is Translated from a Splice Variant "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "mTmc1ex1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " but Not from the Other Variant "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "mTmc1ex2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms21186465"}], "href": "https://doi.org/10.3390/ijms21186465"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32899784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32899784"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Zijing Zhou, Xiaojie Yu, Biaobin Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative Splicing of Three Genes Encoding Mechanotransduction-Complex Proteins in Auditory Hair Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "eNeuro (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/ENEURO.0381-20.2020"}], "href": "https://doi.org/10.1523/ENEURO.0381-20.2020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33509951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33509951"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Maryline Beurg, Lisa A Schimmenti, Alaa Koleilat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New Tmc1 Deafness Mutations Impact Mechanotransduction in Auditory Hair Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2537-20.2021"}], "href": "https://doi.org/10.1523/JNEUROSCI.2537-20.2021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33824189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33824189"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Soichiro Yamaguchi, Maho Kamino, Maho Hamamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cytosolic N-terminal region of heterologously-expressed transmembrane channel-like protein 1 (TMC1) can be cleaved in HEK293 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0287249"}], "href": "https://doi.org/10.1371/journal.pone.0287249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37352201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37352201"}]}]}]}