FAT1 was first reported in relation to autosomal recessive glomerulotubular nephropathy in 2016 (Gee et al., PMID: 26905694). This condition is syndromic, characterized by renal failure and podocyte foot process effacement, as well as cancer, vision anomalies, and brain structural issues. 10 variants (missense, nonsense, frameshift) that have been reported in 14 probands in 4 publications (PMIDs: 26905694, 31831576, 30862798, 34013115) are included in this curation. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by experimental evidence (expression-level evidence, mouse models). Data shows high expression in the kidney (Humphrey's Lab), and mouse models replicate the kidney and eye components of the phenotype (PMIDs: 12724416, 26905694). In summary, there is definitive evidence supporting the relationship between FAT1 and autosomal recessive glomerulotubular nephropathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Glomerulopathy GCEP on the meeting date [11/13/2023] (SOP Version #9).
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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