The POU3F4 gene has been associated with X-linked nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 9/25/2017. This association was made using case-level data only. At least 10 missense, frameshift, nonsense variants have been reported in humans. POU3F4 was first associated with this disease in humans as early as 1995 (de Kok et al.). Association is seen in at least 10 probands in 3 publications (7839145, 7581392, 27941975). Variants in this gene segregated with disease in 6 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence and/or experimental evidence (12 pts.) has been reached. This gene-disease association is supported by a spontaneous mouse model and a null mouse model, both with hearing loss, as well as other relevant expression and protein interaction studies. In summary, POU3F4 is definitively associated with X-linked nonsyndromic hearing loss. This classification was approved by the ClinGen Hearing Loss Working Group on 1/5/2018.
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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