NFE2 was first reported in relation to inherited thrombocytopenia in 2020 (Luk et al, 2020 PMID: 31951293). NFE2 is a DNA binding transcription factor involved in gene expression in erythroid and megakaryocytic cells. To date, there has been one report of a variant in NFE2 causing severe thrombocytopenia with mild effects on erythroid cells. Additionally, somatic variants in NFE2 have been well described in myeloproliferative neoplasms and are not included in this curation. Evidence supporting this gene-disease curation includes case level data and experimental data.
Summary of Case Level Data (2 points): One homozygous frameshift variant causing gene truncation has been reported in a single proband (Luk et al, 2020 PMID: 31951293).
Summary of Experimental Evidence (3.5 points): The gene-disease relationship is supported by expression studies (Andrews et al, 1993 PMID: 8469283), cell culture model system (Lecine et al, 1998 PMID: 9716588) and a mouse model system (Shivdasani el al, 1995 PMID: 7774011).
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 gene-disease relationship was curated by the ClinGen Hemostasis and Thrombosis (H/T) Gene Curation Expert Panel using Gene Clinical Validity Standard Operating Procedures (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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