A Novel NUP85 Variant Expanding the Phenotypic Spectrum of NUP85-Associated Steroid-Resistant Nephrotic Syndrome

KURT ŞÜKÜR E. D., TİMUÇİN E., BAŞTUĞ T., ÖZALTIN F.

CLINICAL GENETICS, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2025
  • Doi Number: 10.1111/cge.14703
  • Journal Name: CLINICAL GENETICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE
  • Hacettepe University Affiliated: Yes

Abstract

Steroid-resistant nephrotic syndrome (SRNS) is a severe kidney disorder linked to over 60 genes, including NUP85, which plays a key role in nuclear pore function and glomerulogenesis. We identified a novel homozygous NUP85 variant (NM_024844.5: c.1379G > A, p.Arg460Gln) in a pediatric SRNS patient who also presented with cleft lip-palate and mild intellectual disability, marking the first reported association of these phenotypes with a NUP85 variant. Molecular dynamics simulations revealed that the variant destabilizes the protein's helix bundle, providing mechanistic insights into its potential pathogenic effects. This study broadens the known phenotypic spectrum of NUP85-related conditions and highlights the value of computational tools, such as molecular dynamics, in unraveling the impact of novel variants.