ZNF341 deficiency in relation to Hyper IgE syndrome 3, autosomal recessive, with recurrent infections, was first reported in 2018 (PMID: 29907691 & 29907690). ZNF341 deficiency is associated with high levels of IgE, eczema, atopic dermatitis, chronic mucocutaneous candidiasis, and recurrent pulmonary infections. ZNF341 is a transcription factor that regulates STAT3 expression; patients with ZNF341 deficiency showed decreased expression and STAT3 function in T lymphocytes. Decrease Th17 subsets characterize the immunologic phenotype of ZNF341 deficient patients. Evidence supporting this gene-disease relationship includes case-level data and experimental evidence. This curation included ten probands from 10 unrelated consanguineous families (PMID: 29907691, 29907690 & 37080116). All the alleles are loss of function with experimental data, except for the allele p.Ser64Ter. Experimentally, this gene-disease relationship is supported by its wide expression in immune cells such as B cells, T cells, monocytes, and basophils and its role in regulating STAT3 expression demonstrated by CHIP-Seq and RNAseq in patient´s cells and in vitro cell models. In summary, ZNF341 is definitively associated with Hyper IgE syndrome 3, autosomal recessive, with recurrent infections. This has been repeatedly demonstrated in research and has been upheld over time. This classification was approved by the ClinGen SCID/CID Working Group on DATE (SOP Version 8).
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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