Variants in the NUP50 gene have been not been reported with disease previously. The NUP50 gene encodes nuclear pore glycoprotein p50, a nuclear pore complex component. The nuclear pore complex spans the nuclear envelope and allows the flow of molecules (proteins, RNA, carbohydrates, lipids and signaling molecules) between the nucleus and cytoplasm. Nuclear pore dysfunction precedes TDP-43 mislocalisation in neurons of sporadic ALS patients, and reciprocally is exacerbated by TDP-43 and FUS aggregation.
A case-control rare variant burden analysis of whole-genome sequencing data identified a burden of 11 damaging variants in NUP50 among FTD/ALS cases compared to controls (PMID: 36670122). Loss-of-function variants in the NUP50 gene have been reported till date in individuals with FTD/ALS (PMIDs: 36670122). In all instances of literature when available, affected probands with NUP50 variants are identified to have dysregulation of protein expression levels (PMIDs: 36670122). There is in vivo data suggesting that deletion of NUP50 gene affects the motor phenotype. The maximum score for genetic evidence through aggregate variant analysis is 3 (Limited 0-6) being reported in the paper by Megat et al (PMID: 36670122).
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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