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However, it is still difficult to explain this heterogeneity perfectly with known deafness genes. Here, we report a novel causative gene EPHA10 as well as its non-coding variant in 5\u2032 untranslated region identified in a family with post-lingual autosomal dominant non-syndromic hearing loss from southern China. One affected member of this family had an ideal hearing restoration after cochlear implantation. We speculated that there were probable deafness-causing abnormalities in the cochlea according to clinical imaging and auditory evaluations. A heterozygous variant c.-81_-73delinsAGC was found co-segregating with hearing loss. Epha10 was expressed in mouse cochlea at both transcription and translation levels. The variant caused upregulation of EPHA10 which may result from promoter activity enhancement after sequence change. Overexpression of Eph (the homolog of human EPHA10) exerted effects on the structure and function of chordotonal organ in fly model. In summary, our study linked pseudo-kinase EPHA10 to hearing loss in humans for the first time.<\/jats:p>","DOI":"10.1093\/hmg\/ddac223","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T17:41:35Z","timestamp":1662054095000},"page":"720-731","source":"Crossref","is-referenced-by-count":6,"title":["A non-coding variant in 5\u2019 untranslated region drove up-regulation of pseudo-kinase EPHA10 and caused non-syndromic hearing loss in humans"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-9356","authenticated-orcid":false,"given":"Sida","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Xiangya Hospital Central South University , Changsha, Hunan 410008 , People's Republic of China"},{"name":"Key Laboratory of Otolaryngology Major Disease Research of Hunan Province , Changsha, Hunan 410008 , People's Republic of China"},{"name":"National Clinical Research Centre for Geriatric Disorders , Department of Geriatrics, Xiangya Hospital, , Changsha, Hunan 410008 , People's Republic of China"},{"name":"Central South University , Department of Geriatrics, Xiangya Hospital, , Changsha, Hunan 410008 , People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Otorhinolaryngology , Head and Neck Surgery, , Changsha, Hunan 410004 , People's Republic of China"},{"name":"University of South China , Head and Neck Surgery, , Changsha, Hunan 410004 , People's Republic of China"},{"name":"The Hengyang Key Laboratory of Cellular Stress Biology , Institute of Cytology and Genetics, Hengyang Medical School, , Hengyang, Hunan 421001 , People's Republic of China"},{"name":"University of South China , Institute of Cytology and Genetics, Hengyang Medical School, , Hengyang, Hunan 421001 , People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Miami Miller School of Medicine , Miami, FL 33136 , USA"},{"name":"Dr. John T. 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