SLC39A7 was first reported in relation to autosomal recessive agammaglobulinemia in 2019 (Anzilotti C, et al., 2019, PMID: 30718914). Hypomorphic mutations in the SLC39A7 gene, encoding ZIP7, cause a human immunodeficiency syndrome characterized by an absence of circulating B cells, agammaglobulinemia and early-onset infections. Seven missense variants have been reported in five probands, and one additional family member, in one publication (PMID: 30718914). This gene-disease association is supported by its function as a zinc transporter (PMID: 14525538) that contributes to proper signal transduction through the (pre-)BCR for the transition from pre-B cell to immature B cell. Functional alteration is found in patient cells in which constitutive phosphatase activity was indeed higher (PMID: 30718914). Additionally, there is a knock-in mouse model that recapitulates disease (PMID: 30718914). 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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