ArticleThe Journal of clinical investigation2018
Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome.
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Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82citing papers in PubMed
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Who cites it
82 citing papers in PubMed, 140 citations in OpenAlex.
- The risk of nephrotic range proteinuria and kidney failure in primary laminopathies is genotype specific.JCI insight · 2026Article
- Gene-disease relationships for glomerular phenotypes: expert recommendations from ClinGen.Nature reviews. Nephrology · 2026Review
- Mechanoresponsive modulation of nuclear pore complex structure and function bybioRxiv : the preprint server for biology · 2026Article
- Pathologies at the gateway: exploring the link between nucleoporins and inherited diseases.Cellular and molecular life sciences : CMLS · 2026Review
- A case of Frasier syndrome achieved complete remission by cyclosporine A for steroid-resistant nephrotic syndrome.CEN case reports · 2025Article
- Analysis of pathological spectrum characteristics in elderly patients with nephrotic syndrome: a comparative study with non-elderly patients.Renal failure · 2025Article
- Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment.Nature communications · 2025Article
- CRISPR-Cas9 HDR optimization: RAD52, denatured, and 5'-modified DNA templates in knock-in mice generation.iScience · 2025Article
- Exploring genotype-phenotype correlation in nucleoporin nephropathy.Pediatric research · 2025Article
- Nuclear mechanics as a determinant of nuclear pore complex plasticity.Nature cell biology · 2025Review
- Loss of Nup155 promotes high fructose-driven podocyte senescence by inhibiting INO80 mRNA nuclear export.Journal of advanced research · 2025Article
- Nucleoporins cooperate with Polycomb silencers to promote transcriptional repression and repair at DNA double-strand breaks.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nuclear pores safeguard the integrity of the nuclear envelope.Nature cell biology · 2025Article
- Genetic and clinical spectrum of steroid-resistant nephrotic syndrome with nuclear pore gene mutation.Pediatric nephrology (Berlin, Germany) · 2025Article
- When should the nephrologist think about genetics in patients with glomerular diseases?Clinical kidney journal · 2025Review
- Nucleoporin-associated steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Candidate Genetic Modifiers in Alport Syndrome: A Case Series.Life (Basel, Switzerland) · 2025Article
- Nup107 contributes to the maternal-to-zygotic transition by preventing the premature nuclear export of pri-miR427.Development (Cambridge, England) · 2025Article
- NovelClinical kidney journal · 2025Article
- Case Report: a novel variant inFrontiers in nephrology · 2025Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
58 authors at 18 institutions in 11 countries.
Daniela A BraunDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Svjetlana LovricDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
David SchapiroDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ronen SchneiderDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jonathan MarquezPediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Maria AsifCologne Center for Genomics, University of Cologne, Cologne, Germany.
Muhammad Sajid HussainCologne Center for Genomics, University of Cologne, Cologne, Germany.
Ankana DagaDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Eugen WidmeierDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jia RaoDepartment of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
Shazia AshrafDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Weizhen TanDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
C Patrick LuskDepartment of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
Amy KolbDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tilman Jobst-SchwanDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Johanna Magdalena SchmidtDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Charlotte A HoogstratenDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kaitlyn EddyDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Thomas M KitzlerDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Shirlee ShrilDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abubakar MoawiaCologne Center for Genomics, University of Cologne, Cologne, Germany.
Kathrin SchrageInstitute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
Arwa Ishaq A KhayyatInstitute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
Jennifer A LawsonDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Heon Yung GeeDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jillian K WarejkoDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tobias HermleDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Amar J MajmundarDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Hannah HugoDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Birgit BuddeCologne Center for Genomics, University of Cologne, Cologne, Germany.
Susanne MotamenyCologne Center for Genomics, University of Cologne, Cologne, Germany.
Janine AltmüllerCologne Center for Genomics, University of Cologne, Cologne, Germany.
Angelika Anna NoegelInstitute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
Hanan M FathyPediatric Nephrology Unit, Alexandria Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
Daniel P GaleCentre for Nephrology, University College London, Royal Free Hospital, London, United Kingdom.
Syeda Seema WaseemCologne Center for Genomics, University of Cologne, Cologne, Germany.
Ayaz KhanHuman Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, Pakistan Institute of Engineering and Applied Sciences, Faisalabad, Pakistan.
Larissa KerecukBirmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom.
Seema HashmiDepartment of Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan.
Nilufar MohebbiDivision of Nephrology, University Hospital Zurich, Zurich, Switzerland.
Robert EttengerDepartment of Pediatrics, University of California, Los Angeles, California.
Erkin SerdaroğluDepartment of Pediatric Nephrology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.
Khalid A AlhasanPediatric Department, College of Medicine, King Saud University and King Khalid University Hospital, Riyadh, Saudi Arabia.
Mais HashemDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Sara GoncalvesLaboratory of Hereditary Kidney Diseases, INSERM UMR1163, Imagine, Institute, Paris, France.
Gema AricetaUniversitat Autonoma de Barcelona, Hospital Universitari Vall d'Hebron, Pediatric Nephrology, Barcelona, Spain.
Mercedes UbetagoyenaHospital Universitario Donostia, Pediatric Nephrology, Donostia-San Sebastian, Spain.
Wolfram AntoninInstitute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, 52074 Aachen, Germany.
Shahid Mahmood BaigHuman Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, Pakistan Institute of Engineering and Applied Sciences, Faisalabad, Pakistan.
Fowzan S AlkurayaDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Qian ShenDepartment of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
Hong XuDepartment of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
Corinne AntignacLaboratory of Hereditary Kidney Diseases, INSERM UMR1163, Imagine, Institute, Paris, France.
Richard P LiftonDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Shrikant ManeDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Peter NürnbergCologne Center for Genomics, University of Cologne, Cologne, Germany.
Mustafa K KhokhaPediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Friedhelm HildebrandtDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Boston Children's Hospital · USUniversity of Cologne · DENational Institute for Biotechnology and Genetic Engineering · PKYale University · USChildren's Hospital of Fudan University · CNDélégation Paris 5 · FRKing Abdulaziz City for Science and Technology · SAAlexandria University · EGBiogipuzkoa Health Research Institute · ESBirmingham Children's Hospital · GBDr. Behçet Uz Çocuk Hastalıkları Hastanesi · TRKing Saud University · SARWTH Aachen University · DESindh Institute of Urology and Transplantation · PKThe Royal Free Hospital · GBUniversitat Autònoma de Barcelona · ESUniversity Hospital of Zurich · CHUniversity of California, Los Angeles · US
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MSkill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0MRenal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI ARONSON, PETER S. · 2008 to 2022
$16.8MYale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0MRESEARCH TRAINING IN PEDIATRIC NEPHROLOGYT32DK007726 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI BRISCOE, DAVID M. · 1994 to 2023
$5.9MNew Mechanisms of Heterotaxy and Congenital Heart Disease: Nucleoporins at CiliaR01HL124402 · NHLBI · YALE UNIVERSITY · PI KHOKHA, MUSTAFA K, LUSK, CHARLES PATRICK · 2015 to 2022
$5.5MIdentification and function of new genes causing childhood nephrotic syndromeR01DK076683 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2007 to 2021
$5.3MHigh Performance Computing Instrumentation for the Yale Center for Genome AnalysisS10OD030363 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2022 to 2022
$1.2MHigh Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890kNHGRI NIH HHS U54 HG006504NHLBI NIH HHS R01 HL124402NIDDK NIH HHS P30 DK079310NIDDK NIH HHS R01 DK076683NIDDK NIH HHS T32 DK007726NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007223NIH HHS S10 OD018521NIH HHS S10 OD030363
Abstract
Steroid-resistant nephrotic syndrome (SRNS) almost invariably progresses to end-stage renal disease. Although more than 50 monogenic causes of SRNS have been described, a large proportion of SRNS remains unexplained. Recently, it was discovered that mutations of NUP93 and NUP205, encoding 2 proteins of the inner ring subunit of the nuclear pore complex (NPC), cause SRNS. Here, we describe mutations in genes encoding 4 components of the outer rings of the NPC, namely NUP107, NUP85, NUP133, and NUP160, in 13 families with SRNS. Using coimmunoprecipitation experiments, we showed that certain pathogenic alleles weakened the interaction between neighboring NPC subunits. We demonstrated that morpholino knockdown of nup107, nup85, or nup133 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 NUP107, NUP85, or NUP133 in podocytes activated Cdc42, an important effector of SRNS pathogenesis. CRISPR/Cas9 knockout of nup107 or nup85 in zebrafish caused developmental anomalies and early lethality. In contrast, an in-frame mutation of nup107 did not affect survival, thus mimicking the allelic effects seen in humans. In conclusion, we discovered here that mutations in 4 genes encoding components of the outer ring subunits of the NPC cause SRNS and thereby provide further evidence that specific hypomorphic mutations in these essential genes cause a distinct, organ-specific phenotype.
Indexed as
AnimalsCell LineDisease Models, AnimalGene Knockdown TechniquesHumansNephrotic SyndromeNuclear Pore Complex ProteinsXenopus laevisXenopus ProteinsZebrafishZebrafish ProteinsNuclear Pore Complex ProteinsXenopus ProteinsZebrafish ProteinsGeneticsMonogenic diseasesNephrology
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