In this report,we identified a homozygous missense mutation in a novel gene,TMEM132E (transmembrane protein 132E),in a chinese consanguineous family with nonsyndromic hearing loss using whole exome sequencing combined with homozygosity mapping.After filtering out the variants using the data from dbSNP131,the 1000 Genomes Project,and HapMap databases,only a single deleterious mutation remained in the homozygous region co-segregate with the phenotype.To test the population frequency,we genotyped 600 Chinese Han controls and did not find a carrier of this mutation in these controls.We further sequenced the coding region of TMEM132E in 95 unrelated affected individuals,no disease causing mutation was found,possibly suggesting this nonsyndromic hearing loss is very rare in Chinese population.The homozygous missense mutation c.1259G>A leads to a Arg to Gin change(p.Arg420Gln)which is highly conserved across the species.SIFT and PolyPhen-2 prediction results revealed that the change is detrimental to protein function.So far,very little is known about TMEM132E function.To investigate its potential role in the development of inner ear and pathogenesis of hearing loss,several in vivo and in vitro studies were conducted.qPCR and immunofluorescence results showed that TMEM132E was expressed primarily in the inner ear hair cells although it expressed in many tissues.In addition,we used morpholino-mediated knockdown of its zebrafish ortholog,Tmie132e.We found that Tmie132e knockdown in zebrafish resulted in morphological and developmental defects of the inner ear hair cells and imbalanced swimming motion.Co-Injection of human wild-type TMEM132E mRNA but not the mutant TMEM132E mRNA could rescue the phenotype partially.Our results strongly suggested that TMEM132E is a novel hearing loss gene.