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Abstract: FR-PO1005

GAS2L2 as a Candidate Gene for Nephrotic Syndrome

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic


  • Widmeier, Eugen, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Hugo, Hannah, Boston Children's Hospital, Boston, Massachusetts, United States
  • Shril, Shirlee, Boston Childrens Hospital, Boston, Massachusetts, United States
  • Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Steroid resistant nephrotic syndrome (SRNS) inevitably progresses to end-stage renal disease (ESRD) within the first three decades of life requiring dialysis or transplantation for survival. To date discovery of more than 50 different monogenic causes of SRNS has helped to elucidate the pathogenesis of SRNS.


To identify novel mongenic causes of NS, we performed whole exome sequencing, homozygosity mapping, and targeted exon sequencing. To investigate molecular mechanisms of a newly identified monogenic cause of NS in vitro, we generated immortalized human podocyte cell lines with stable knockdown of the GAS2L2 gene.


By next-generation sequencing, we identified a homozygous recessive missense mutation in a region of high evolutionary conservation (Drosophila melanogaster) within the GAS2 domain of GAS2L2 gene (c.817C>T, p.Arg273Cys) in a patient with early onset NS. GAS2L2 is a known linker between actin filaments and microtubules. We show that GFP-GAS2L2 localizes to the cytoskeleton filaments and that knockdown of GAS2L2 results in severe defect of podocytes migration rate.


We discovered a recessive mutation of GAS2L2 as a likely novel monogenic cause of early-onset SRNS. We propose that the disease phenotype is caused by defect of crosstalk between actin filaments and microtubules.


  • Other NIH Support