FANCL is one of the 23 Fanconi anemia (FA) or FA-like genes known to cause autosomal recessive FA, which is a group of rare genetic disorders characterized by bone marrow failure, predisposition to cancer, and congenital abnormalities. FANCL gene encodes a ubiquitin ligase that was first reported in 2003 to be a member of the Fanconi Anemia Complex (Meetei et al. PMID: 12973351). Various types of variants (e.g. in-frame indel, frameshift, insertion, putative synonymous, etc.) that have been reported in multiple unrelated probands in publications (PMID:12973351,19405097,25754594,31513304). A putative synonymous c.1107G>A, p.Lys369= (NM_001114636.1 ) variant was demonstrated to induce aberrant splicing and was suggested to be a founder mutation in the South Asian population (PMID: 31513304). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is FANCL protein loss of function. This gene-disease relationship is further supported by FANCL-deficient patient cell lines, rescue cell culture model, protein interaction and expression studies. In summary, FANCL is definitively associated with autosomal recessive FA complementation group L. 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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