FANCF is one of the 23 FA or FA-like genes known to cause autosomal recessive Fanconi anemia (FA) characterized by bone marrow failure, developmental abnormalities, cancer predisposition, and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C. The cloning of the cDNA encoding FANCF by complementation of an FA-F cell line was first reported in 2000 (PMID:10615118). Fourteen different pathogenetic homozygous or compound heterozygous variants of FANCF account for approximately 2 to 3% of the affected individuals (PMID: 31288759). Disease-associated variants have been reported throughout the single coding exon of the FANCF gene. The most commonly seen FANCF variants are short frameshift deletions, resulting in premature termination of the protein, suggesting homozygous loss of function is the mechanism of tumorigenesis for this disorder (PMID: 10615118, 16084127, 31288759, 26033879, 27714961). This gene-disease relationship is further supported by FANCF-deficient mouse model, rescue cell culture model, protein interaction and expression studies. In summary, FANCF is definitively associated with FA complementation group F. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.
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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