GRXCR2 was first reported in relation to autosomal recessive nonsyndromic hearing loss in 2014 by Imtiaz et al. One missense variant occurring in the last exon and resulting in an extension has been reported to segregate with disease in a family with hearing loss. Evidence supporting this gene-disease relationship includes case-level data, segregation data and experimental data. This gene-disease association is supported by multiple mouse models, functional alteration studies, protein interaction studies indicating that GRXCR2 interacts with TPRN, and inner ear expression studies (Avenarious et al. 2012, 30157177; Avenarius 2012, a PhD thesis; Liu et al. 2018, 30380417). In summary, there is moderate evidence to support this gene-disease association. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Hearing Loss Working Group on 3/26/2021.
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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