UNG was first reported in relation to autosomal hyper-IgM (HIGM) syndrome type 5 in 2003 (Imai K, et al., 2003, PMID: 12958596). Characteristics of HIGM include susceptibility to bacterial infections, lymphoid hyperplasia, increased serum IgM concentrations and profoundly decreased serum IgG and IgA concentrations. Six variants (3 frameshift, 2 missense, and 1 single amino acid deletion) have been reported in five probands in three publications (PMIDs: 12958596, 32135276, 23585684). This gene-disease association is supported by its function as an uracil-DNA glycosylase (PMID: 12214226) with a role in class switch recombination. Additionally, UNG deficiency is linked to a profound inability of human B cells to undergo immunoglobulin class switch recombination in association with qualitative consequences for the pattern of somatic hypermutation (PMID: 12958596) and a mouse model that recapitulates disease (PMID: 12401169). In summary, there is moderate 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.
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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