The H4C5 gene is located on chromosome 6 at 6p22.2 and encodes the H4 clustered histone 5 protein, a core component of nucelosomes. H4C5 was first reported in relation to autosomal dominant Tessadori-Bicknell-van Haaften neurodevelopmental syndrome 3 (TEVANED3) in 2022 (Tessadori et al., PMID: 35202563). TEVANED3 is characterized by intellectual disability/global developmental delay, hypotonia, seizure, microcephaly and short stature. To date, 7 missense variants, including 4 unique and 3 recurrent variants in 18 probands have been reported in two publications and are included in this curation (PMID 35202563; 36987712). Experimental evidence to support this gene-disease relationship association is from expression and protein interaction data at present. In summary, there is strong evidence to support the relationship between H4C5 and autosomal dominant TEVANED3. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date March 19, 2024 (SOP Version 10.0).
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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