ArticleNature communications2018
Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment.
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Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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74citing papers in PubMed, 1 pooled it
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency.Journal of lipid research · 2022Pooled it
- Gene-disease relationships for glomerular phenotypes: expert recommendations from ClinGen.Nature reviews. Nephrology · 2026Review
- Hypothalamic-pituitary deficiency after radiation in childhood cancer survivors is associated with rare variants in TNS2.The Journal of clinical endocrinology and metabolism · 2026Article
- Identification of monogenic variants in steroid-resistant and steroid-sensitive nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Article
- Article
- Integrating machine learning and GWAS for variant prioritization in the INCIPE cohort highlights ABC transporter genes in chronic kidney disease.Frontiers in genetics · 2026Article
- Emerging genetic mechanisms of glomerular proteinuria: a podocyte-centered multi-layer network perspective.Frontiers in genetics · 2026Review
- Serum RAC1 as a potential biomarker in the early stages of diabetic kidney disease.Diabetology & metabolic syndrome · 2025Article
- Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment.Nature communications · 2025Article
- Patient-specific hiPSC-Podocytes as an in vitro model of genetic FSGS.Scientific reports · 2025Article
- Exome Sequencing in Saudi Arabian Pediatric Kidney Disease Single-Center Cohort.Kidney international reports · 2025Article
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- The intelligent podocyte: sensing and responding to a complex microenvironment.Nature reviews. Nephrology · 2025Review
- The differential expression of MAGI2 in glomerulopathies and its application as a molecular discriminator of podocytopathies.Journal of translational medicine · 2025Article
- Nephron progenitor fate is modulated by angiotensin type 1 receptor signaling in human kidney organoids.Stem cells (Dayton, Ohio) · 2025Article
- Mechanisms of podocyte injury in genetic kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- Genetic aspects of pediatric nephrotic syndrome and anti-nephrin antibodies.Clinical and experimental nephrology · 2025Review
- Advances in focal segmental glomerulosclerosis research: genetic causes to non-coding RNAs.Molecular biology reports · 2025Review
- When should the nephrologist think about genetics in patients with glomerular diseases?Clinical kidney journal · 2025Review
- Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
65 authors at 20 institutions in 14 countries.
Shazia AshrafDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Hiroki KudoDepartment of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Jia RaoDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Atsuo KikuchiDepartment of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.ORCID http://orcid.org/0000-0003-1002-8739
Eugen WidmeierDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jennifer A LawsonDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Weizhen TanDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Tobias HermleDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jillian K WarejkoDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Shirlee ShrilDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Merlin AirikDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Tilman Jobst-SchwanDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Svjetlana LovricDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Daniela A BraunDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Heon Yung GeeDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8741-6177
David SchapiroDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Amar J MajmundarDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Carolin E SadowskiDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Werner L PabstDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Ankana DagaDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Amelie T van der VenDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Johanna M SchmidtDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Boon Chuan LowDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Anjali Bansal GuptaMechanobiology Institute, National University of Singapore, Singapore, Singapore.
Brajendra K TripathiLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Jenny WongDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Kirk CampbellDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Kay MetcalfeManchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Denny SchanzeInstitute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.ORCID http://orcid.org/0000-0003-2748-9929
Tetsuya NiihoriDepartment of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Hiroshi KaitoDepartment of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Kandai NozuDepartment of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Hiroyasu Tsukaguchi2nd Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-machi, Hirakata-shi, Osaka, 573-1191, Japan.
Ryojiro TanakaDepartment of Nephrology, Hyogo Prefectural Kobe Children's Hospital, 1-6-7 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.ORCID http://orcid.org/0000-0002-7924-6876
Kiyoshi HamahiraDepartment of Pediatrics, Himeji Red Cross Hospital, 1-12-1 Shimoteno, Himeji, Hyogo, 670-8540, Japan.
Yasuko KobayashiDepartment of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Takumi TakizawaDepartment of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Ryo FunayamaDivision of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan.
Keiko NakayamaDivision of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan.
Yoko AokiDepartment of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Naonori KumagaiDepartment of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Kazumoto IijimaDepartment of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Henry FehrenbachDepartment of Pediatric Nephrology, Children's Hospital, Memmingen, Germany.
Jameela A KariPediatric Nephrology Center of Excellence and Pediatric Department, King Abdulaziz University, Jeddah, Saudi Arabia.
Sherif El DesokyPediatric Nephrology Center of Excellence and Pediatric Department, King Abdulaziz University, Jeddah, Saudi Arabia.
Sawsan JalalahPathology Department, King Abdulaziz University, Jeddah, Saudi Arabia.
Radovan BogdanovicInstitute for Mother and Child Health Care of Serbia "Dr Vukan Čupić", Department of Nephrology, University of Belgrade, Faculty of Medicine, Belgrade, 11000, Serbia.
Nataša StajićInstitute for Mother and Child Health Care of Serbia "Dr Vukan Čupić", Department of Nephrology, University of Belgrade, Faculty of Medicine, Belgrade, 11000, Serbia.
Hildegard ZappelDepartment for Paediatrics II, University of Göttingen, Göttingen, Germany.
Assel RakhmetovaDepartment of Nephrology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
Sharon-Rose WassmerDepartment of Nephrology, Luzerner Kantonsspital, Lucerne, Switzerland.
Therese JungraithmayrDepartment of Pediatrics, University Medical Center Innsbruck, Innsbruck, Austria.
Juergen StrehlauDepartment of Pediatric Nephrology, Hannover Medical School, Hannover, Germany.
Aravind Selvin KumarDepartment of Pediatric Nephrology and Medical Genetics, Institute of Child Health and Hospital for Children, TN Dr.M.G.R. Medical University, Chennai, India.
Arvind BaggaDivision of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Neveen A SolimanDepartment of Pediatrics, Center of Pediatric Nephrology & Transplantation, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.
Shrikant M ManeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, 06510, USA.
Lewis KaufmanDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Douglas R LowyLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Mohamad A JairajpuriDepartment of Biosciences, Jamia Millia Islamia, New Delhi, India.
Richard P LiftonDepartment of Genetics, Yale University School of Medicine, New Haven, CT, 06510, USA.
York PeiDivision of Nephrology, University Health Network, and University of Toronto, Toronto, ON, Canada.
Martin ZenkerInstitute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
Shigeo KureDepartment of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. kure@med.tohoku.ac.jp.
Friedhelm HildebrandtDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. friedhelm.hildebrandt@childrens.harvard.edu.ORCID http://orcid.org/0000-0002-7130-0030
Boston Children's Hospital · USTohoku University · JPIcahn School of Medicine at Mount Sinai · USKing Abdulaziz University · SAKobe University · JPGunma University · JPNational Institutes of Health · USNational University of Singapore · SGUniversity Hospital Magdeburg · DEUniversity of Belgrade · RSYale University · USAll India Institute of Medical Sciences · INCairo University · EGHimeji Red Cross Hospital · JPInnsbruck Medical University · ATJamia Millia Islamia · INKansai Medical University · JPKazakh National Medical University · KZKernkraftwerk Gundremmingen · DEKobe Children's Hospital · JP
Funding
Renal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI ARONSON, PETER S. · 2008 to 2022
$16.8MTumor gene expression in vitro and in vivoZIABC008905 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LOWY, DOUGLAS R. · 2009 to 2025
$14.3MRESEARCH TRAINING IN PEDIATRIC NEPHROLOGYT32DK007726 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI BRISCOE, DAVID M. · 1994 to 2023
$5.9MIdentification and function of new genes causing childhood nephrotic syndromeR01DK076683 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2007 to 2021
$5.3MMount Sinai Nephrology Research Training GrantT32DK007757 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CAMPBELL, KIRK N, HE, JOHN CIJIANG · 1998 to 2022
$3.8MThe role of dendrin in glomerular disease progressionR01DK103022 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CAMPBELL, KIRK N · 2015 to 2019
$1.9MHigh 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
$890kNIDDK NIH HHS P30 DK079310NIDDK NIH HHS R01 DK076683NIDDK NIH HHS R01 DK103022NIDDK NIH HHS T32 DK007726NIDDK NIH HHS T32 DK007757NIH HHS S10 OD018521NIH HHS S10 OD030363
Abstract
No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.
Indexed as
AdultAnimalsChildChild, PreschoolDisease Models, AnimalDNA Mutational AnalysisDrug ResistanceExome SequencingFemaleGene Knockdown TechniquesGlucocorticoidsHEK293 CellsHigh-Throughput Nucleotide SequencingHumansInfantMaleGlucocorticoidsrhoA GTP-Binding ProteinRNA, Small Interfering
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