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NUP107 – familial idiopathic steroid-resistant nephrotic syndrome

Biallelic NUP107 variants have been reported in two unrelated female patients presenting with early-onset familial idiopathic steroid-resistant nephrotic syndrome (SRNS). In a cohort of four SRNS cases carrying nucleoporin mutations, two harbored NUP107 alleles predicted to cause premature termination or frameshift truncation (PMID:38650033). All affected individuals presented between 1 and 10.5 years (median 5.08 years) and both NUP107 cases progressed rapidly to end-stage kidney disease by a median age of 7 years, with kidney biopsies demonstrating focal segmental glomerulosclerosis (PMID:38650033).

NUP107 encodes a core component of the nuclear pore complex in podocytes, and biallelic loss-of-function variants are presumed to disrupt nucleo-cytoplasmic transport, leading to podocyte injury and nephrotic syndrome. No segregation beyond the index cases has been reported, and disease-relevant functional assays for NUP107 variants in podocyte models are currently lacking.

Key Take-home: Biallelic truncating NUP107 variants underlie autosomal recessive familial idiopathic SRNS, supporting inclusion of NUP107 in genetic testing panels for early-onset nephrotic syndrome.

References


Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Two unrelated probands with biallelic truncating NUP107 variants; no extended segregation data; single cohort report

Genetic Evidence

Limited

Two probands with predicted loss-of-function variants in NUP107 meet minimal case count for ClinGen evidence

Functional Evidence

No reported evidence

No disease-relevant functional assays for NUP107 variants in podocyte or renal models