{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:26:40Z","timestamp":1788323200072,"version":"build-2803163510"},"reference-count":23,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"NIDCD","doi-asserted-by":"crossref","award":["R01 DC018583-01"],"award-info":[{"award-number":["R01 DC018583-01"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hearing Research, Inc","award":["Generation of cell lines to underst"],"award-info":[{"award-number":["Generation of cell lines to underst"]}]},{"name":"Hearing Research, Inc","award":["TMTC4,a novel human deafness gene"],"award-info":[{"award-number":["TMTC4,a novel human deafness gene"]}]},{"name":"Basic Science Research Program","award":["2021R1C1C1007980,2021R1A2C2092038"],"award-info":[{"award-number":["2021R1C1C1007980,2021R1A2C2092038"]}]},{"name":"Intramural SNUBH Research Fund","award":["13-2022-0010"],"award-info":[{"award-number":["13-2022-0010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,22]]},"abstract":"<jats:p>\n                    Transmembrane and tetratricopeptide repeat 4 (\n                    <jats:italic>Tmtc4<\/jats:italic>\n                    ) is a deafness gene in mice.\n                    <jats:italic>Tmtc4<\/jats:italic>\n                    -KO mice have rapidly progressive postnatal hearing loss due to overactivation of the unfolded protein response (UPR); however, the cellular basis and human relevance of\n                    <jats:italic>Tmtc4<\/jats:italic>\n                    -associated hearing loss in the cochlea was not heretofore appreciated. We created a hair cell\u2013specific conditional KO mouse that phenocopies the constitutive KO with postnatal onset deafness, demonstrating that\n                    <jats:italic>Tmtc4<\/jats:italic>\n                    is a hair cell\u2013specific deafness gene. Furthermore, we identified a human family in which\n                    <jats:italic>Tmtc4<\/jats:italic>\n                    variants segregate with adult-onset progressive hearing loss. Lymphoblastoid cells derived from multiple affected and unaffected family members, as well as human embryonic kidney cells engineered to harbor each of the variants, demonstrated that the human\n                    <jats:italic>Tmtc4<\/jats:italic>\n                    variants confer hypersensitivity of the UPR toward apoptosis. These findings provide evidence that\n                    <jats:italic>TMTC4<\/jats:italic>\n                    is a deafness gene in humans and further implicate the UPR in progressive hearing loss.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.172665","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T19:08:37Z","timestamp":1699902517000},"source":"Crossref","is-referenced-by-count":7,"title":["TMTC4 is a hair cell\u2013specific human deafness gene"],"prefix":"10.1172","volume":"8","author":[{"given":"Jiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology and"},{"name":"Department of Pediatrics, Institute of Human Genetics, Weill Institute for Neurosciences, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5125-2118","authenticated-orcid":true,"given":"Byung Yoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5098-5424","authenticated-orcid":true,"given":"Yasmin","family":"Eltawil","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura","family":"Ismail Mohamad","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-1297","authenticated-orcid":true,"given":"Yesai","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seoul, South Korea."},{"name":"Department of Otorhinolaryngology, Chungnam National University College of Medicine, Chungnam National University Sejong Hospital, Sejong City, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-2171","authenticated-orcid":true,"given":"Bong Jik","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Chungnam National University College of Medicine, Chungnam National University Sejong Hospital, Sejong City, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott H.","family":"Sherr","sequence":"additional","affiliation":[{"name":"Department of Neurology and"},{"name":"Department of Pediatrics, Institute of Human Genetics, Weill Institute for Neurosciences, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan K.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97498"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708319114"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2015.07.003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167850"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75058-w"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1159\/000480346"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.108"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4559-12.2013"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39678"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201429"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.014068"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000624"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5083-14.2015"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9549"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2016.1444"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00595-4"},{"key":"B17","unstructured":"[No authors listed]. 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