SLC22A4 was first reported in relation to autosomal recessive nonsyndromic hearing loss in 2016 (Ben Said et al., PMID: 27023905). 1 recurrent variant (missense, p.Cys113Tyr) that has been reported in at least 3 probands in 3 publications is included in this curation. The variant segregated with disease in 5 members from 1 family (PMIDs: 27023905, 33643381, 34194829). The mechanism of pathogenicity appears to be loss-of-function based on in-vitro studies looking at channel function for p.Cys113Tyr (PMID: 27023905). This gene-disease relationship is also supported by experimental evidence. Expression-level data from the gEAR database indicates solid expression in the cochlear duct and pillar cells in the organ of Corti. 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 classification was approved by the ClinGen Hearing Loss GCEP on the meeting date 9/17/2025 (SOP Version 11).
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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