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Biallelic variants in NUP160 have been reported in autosomal recessive familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006). In a multi-patient cohort, one child carried a homozygous c.1235A>C (p.Asp412Ala) variant and developed early-onset SRNS progressing to ESKD by age 7 (PMID:38650033). In an unrelated non-consanguineous pedigree, compound-heterozygous truncating variants c.3943G>T (p.Glu1315Ter) and c.991C>T (p.Arg331Ter) segregated with disease in two siblings, one additional affected relative confirmed by segregation analysis (PMID:30910934). Across these reports, three probands and one segregated sibling demonstrate a consistent autosomal recessive inheritance.
Functional studies in PMID:30910934 employed Drosophila nephrocyte-specific knockdown of NUP160, resulting in reduced cell size, nuclear volume defects, and disrupted nuclear envelope organization. All phenotypes were fully rescued by wild-type human NUP160 but not by the p.Glu1315Ter allele, consistent with a loss-of-function mechanism. These data establish NUP160’s essential role in podocyte biology and support its inclusion in SRNS diagnostic panels. Key Take-home: Loss-of-function NUP160 variants underlie autosomal recessive SRNS and can be functionally validated in vivo, informing molecular diagnosis and management.
Gene–Disease AssociationLimited2 probands with biallelic NUP160 variants and segregation in 1 additional sibling; small cohort size. Genetic EvidenceLimitedBiallelic variants observed in three affected individuals across two unrelated families; segregation confirmed in one relative. Functional EvidenceModerateDrosophila nephrocyte model demonstrates loss-of-function phenotypes rescued by wild-type but not mutant NUP160. |