TMEM132E was first reported in relation to autosomal recessive nonsyndromic hearing loss (ARNSHL) in 2003 (Cheng et al., 12673573). The proposed disease mechanism is loss of function. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Three variants (all missense) have been reported in two probands in two publications (PMIDs: 25331638, 31656313) for a genetic evidence score of 1.75 points. Variants in this gene segregated with disease in 2 additional family members (PMID: 31656313). This gene-disease association is supported by animal models and an expression study (PMIDs: 25331638, 31656313) detailing expression of TMEM132E in the mouse cochlea, phenocopied ARNHL in Zebrafish, and wild type rescue of the phenotype seen in Zebrafish whereas the variant seen in the proband (PMID: 25331638) did not. This resulted in an experimental evidence score of 3.5 points. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the Hearing Loss Gene Curation Expert Panel on 11/21/2017 (SOP Version 5). It was reevaluated with the addition of one publication (PMID: 31656313) on 1/19/2022 (SOP v8). As a result of this reevaluation, the classification did not change.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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