Proteinuric renal disease

Gene: NUP85

Green List (high evidence)

Comment on list classification: 3 families with SRNS and variants in NUP85. Some functional data from Xenopus which shows nup85 involved in glomerulogenesis

Created: 31 Mar 2019, 9:37 p.m.

In OMIM this gene is associated with Nephrotic syndrome, type 17 (618176).

PMID: 30179222 - Braun et al 2018 - 4 individuals from 3 unrelated families with SRNS (families A5195, A3259, and NCR3227/3310) were found to have variants in NUP85 by high-throughput exon sequencing. Two mutations were homozygous missense mutations (c.1430C>T, p.Ala477Val, and c.1933C>T, p.Arg645Trp). One family (NCR3227/3310) carried 2 compound heterozygous alleles (c.405+1G>A and c.1741G>C, p.Ala581Pro), which segregated from the maternal and the paternal side, respectively. Variants found to segregate in the 2 families from which parental DNA was available for study. All families had SRNS and microscopic hematuria. Family NCR3227/3310 additionally displayed intellectual disability, but showed no structural brain defects.

Functional data - morpholino knockdown of nup85 in Xenopus disrupted glomerulogenesis. Re-expression of WT mRNA, but not of mRNA reflecting mutations from SRNS patients, mitigated this phenotype. We furthermore found that CRISPR/Cas9 knockout of NUP85 in podocytes activated Cdc42, an important effector of SRNS pathogenesis.

Created: 31 Mar 2019, 9:36 p.m.

This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: NUP85; Suggested initial gene rating: green; Evidence for inclusion: PMID: 30179222; Other comments: Three families with SRNS reported with rare AR NUP85 variants.

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 17 #618176

Publications

• PMID: 30179222