ArticleNature communications2023
Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45citing papers in PubMed
12.5field-weighted citation impact, top 1% of its field
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Who cites it
45 citing papers in PubMed, 63 citations in OpenAlex.
- Update on APOL1 and chronic kidney diseases in children.Pediatric nephrology (Berlin, Germany) · 2026Review
- APOL1 and chronic kidney disease in pediatrics: a study from the Biorepository and Integrative Genomics Initiative.Pediatric nephrology (Berlin, Germany) · 2026Article
- Coding, modifier, and regulatory effects shape circulating APOL1 levels.Human molecular genetics · 2026Article
- APOL1 kidney disease: a critical narrative review of molecular mechanisms, clinical heterogeneity, and the emerging therapeutic landscape.International urology and nephrology · 2026Review
- Blood pressure andClinical kidney journal · 2026Article
- Long-Read Sequencing in CKD Diagnostics: Breaking Genomic Barriers and Expanding Global Inclusion.Kidney international reports · 2026Review
- APOL1 kidney risk variants and outcomes in children with congenital anomalies of the kidney and urinary tract.Pediatric nephrology (Berlin, Germany) · 2026Article
- Case report of a child with kidney disease: consideration of the risk of a single APOL1 G2 allele with a protective N264K variant on the G0 parental chromosome.BMC nephrology · 2026Article
- Apolipoproteins L involvement in immunity.Journal of human immunity · 2026Review
- Framework for Apolipoprotein 1-Mediated Kidney Disease Classification.Kidney international reports · 2026Article
- The APOL1 variant p.N264K is predicted to block ion flow by occluding a pore at the cell surface.Life science alliance · 2026Article
- Proteomic risk score for early prediction of kidney disease progression in individuals with APOL1 high-risk genotypes.Nature medicine · 2026Article
- Nephrotic syndrome genomic discovery in the Mass General Brigham Biobank identifies monoallelic MEFV variants as a risk factor for focal segmental glomerulosclerosis.Kidney international · 2026Article
- Article
- Precision Diagnosis in APOL1 Kidney Disease With the p.N264K M1 Protective Variant.JAMA network open · 2026Article
- Genetic testing in chronic kidney disease of uneXplained cause (CKDx): clinical insights and evolving diagnostic paradigms.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- APOL1 kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney international · 2025Article
- Using Large Genomic Biobanks to Generate Insights into Genetic Kidney Disease.Seminars in nephrology · 2025Review
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Authors and funding
80 authors at 20 institutions in 7 countries.
Yask GuptaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
David J FriedmanNephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Michelle T McNultyDivision of Pediatric Nephrology, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0002-2080-0940
Atlas KhanDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-6651-2725
Brandon LaneDivision of Nephrology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0002-1158-1117
Chen WangDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0001-9127-0054
Juntao KeDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Gina JinDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Benjamin WoodenDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Andrea L KnobNephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID 0009-0007-6477-0724
Tze Y LimDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Gerald B AppelDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Kinsie HugginsDivision of Nephrology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Lili LiuDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-2622-9669
Adele MitrottiDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePre-J) Nephrology, Dialysis and Transplantation Unit, University of Bari Aldo Moro, Bari, Italy.
Megan C StanglDivision of Nephrology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Andrew BombackDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Rik WestlandDepartment of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.ORCID 0000-0003-4960-4078
Monica BodriaDivision of Nephrology and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Maddalena MarasaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-0712-2329
Ning ShangDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0001-7040-5204
David J CohenDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Russell J CrewDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
William MorelloPediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy.ORCID 0000-0002-4833-4128
Pietro CanettaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-1130-5486
Jai RadhakrishnanDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Jeremiah MartinoDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Qingxue LiuDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Wendy K ChungDepartments of Pediatrics and Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-3438-5685
Angelica EspinozaCenter for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Yuan LuoCenter for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Wei-Qi WeiDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0003-4985-056X
Qiping FengDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-6213-793X
Chunhua WengDepartment of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-9624-0214
Yilu FangDepartment of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-2681-1931
Iftikhar J KulloAtherosclerosis and Lipid Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-6524-3471
Mohammadreza NaderianAtherosclerosis and Lipid Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
Nita LimdiDepartment of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Marguerite R IrvinDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Hemant TiwariDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Sumit MohanDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-5305-9685
Maya RaoDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Geoffrey K DubeDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Ninad S ChaudharyDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Orlando M GutiérrezDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Suzanne E JuddDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Mary CushmanDepartment of Medicine and Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0002-7871-6143
Leslie A LangeDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ethan M LangeDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Daniel L BivonaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Miguel VerbitskyDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-7066-0552
Cheryl A WinklerCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health and Basic Research Program, Frederick National Laboratory, Frederick, MD, USA.ORCID 0000-0001-5552-0917
Jeffrey B KoppKidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.ORCID 0000-0001-9052-186X
Dominick SantorielloDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Ibrahim BatalDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-0686-5457
Sérgio Veloso Brant PinheiroUniversidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Laboratório Interdisciplinar de Investigação Médica, Departamento de Pediatria, Unidade de Nefrologia Pediátrica, Belo Horizonte, MG, Brazil.
Eduardo Araújo OliveiraUniversidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Laboratório Interdisciplinar de Investigação Médica, Departamento de Pediatria, Unidade de Nefrologia Pediátrica, Belo Horizonte, MG, Brazil.
Ana Cristina Simoes E SilvaUniversidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Laboratório Interdisciplinar de Investigação Médica, Departamento de Pediatria, Unidade de Nefrologia Pediátrica, Belo Horizonte, MG, Brazil.ORCID 0000-0001-9222-3882
Isabella PisaniNephrology Unit, Parma University Hospital, and Department of Medicine and Surgery, University of Parma, Parma, Italy.
Enrico FiaccadoriNephrology Unit, Parma University Hospital, and Department of Medicine and Surgery, University of Parma, Parma, Italy.
Fangming LinDivision of Pediatric Nephrology, Department of Pediatrics, Columbia University, New York, NY, USA.ORCID 0000-0003-0858-5472
Loreto GesualdoDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePre-J) Nephrology, Dialysis and Transplantation Unit, University of Bari Aldo Moro, Bari, Italy.
Antonio AmorosoImmunogenetics and Transplant Biology Service, University Hospital "Città della Salute e della Scienza di Torino", Department of Medical Sciences, University of Turin, Turin, Italy.ORCID 0000-0002-9437-9407
Gian Marco GhiggeriDivision of Nephrology and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy.ORCID 0000-0003-3659-9062
Vivette D D'AgatiDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Riccardo MagistroniSurgical, Medical and Dental Department of Morphological Sciences, Section of Nephrology, University of Modena and Reggio Emilia, Modena, Italy.ORCID 0000-0002-3319-0248
Eimear E KennyInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8532-5087
Giovanni MontiniPediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy.ORCID 0000-0002-7350-4475
Friedhelm HildebrandtHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-7130-0030
Dirk S PaulCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-8230-0116
Slavé PetrovskiCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-1527-961X
David B GoldsteinInstitute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-1111-2820
Matthias KretzlerDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Rasheed GbadegesinDivision of Nephrology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0001-5641-6644
Ali G GharaviDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-2801-233X
Krzysztof KirylukDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-5047-6715
Matthew G SampsonHarvard Medical School, Boston, MA, USA.ORCID 0000-0001-9560-076X
Martin R PollakNephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Simone Sanna-CherchiDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA. ss2517@cumc.columbia.edu.ORCID 0000-0002-6185-948X
Columbia University Irving Medical Center · USUniversity of Alabama at Birmingham · USDuke University · USBeth Israel Deaconess Medical Center · USUniversidade Federal de Minas Gerais · BRAstraZeneca (United Kingdom) · GBBroad Institute · USColumbia University · USFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITIstituto Giannina Gaslini · ITMayo Clinic in Florida · USNorthwestern University · USUniversity of Bari Aldo Moro · ITUniversity of Colorado Anschutz Medical Campus · USUniversity of Parma · ITVanderbilt University Medical Center · USBoston Children's Hospital · USEmma Kinderziekenhuis · NLNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · US
Funding
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MVCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0MThe Impact of COVID-19 on People Living with Rare Diseases and Their FamiliesU2CTR002818 · NCATS · CINCINNATI CHILDRENS HOSP MED CTR · PI Maurizio Macaluso · 2019 to 2026
$51.2MJH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2MA Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4MTraining Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GIPSON, DEBBIE S · 2009 to 2023
$20.3MThe eMERGE Risk Assessment Network - Coordinating CenterU01HG011166 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Niall John Lennon, Joseph F. Peterson · 2020 to 2026
$16.8MGenomic Basis of Susceptibility to COVID-19 Infection and its ComplicationsU01HG006379 · NHGRI · MAYO CLINIC ROCHESTER · PI Richard R. Sharp · 2011 to 2026
$16.5MFinding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6MVariation, Function, and Disease Supplement ProgramU01HG008657 · NHGRI · UNIVERSITY OF WASHINGTON · PI David Russell Crosslin, Gail Pairitz Jarvik · 2015 to 2026
$13.4MOMOP information model for eMERGE phenotypingU01HG008680 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wendy K Chung, GEORGE M HRIPCSAK · 2015 to 2026
$13.3MCureGNU24DK100845 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRYSTAL A. GADEGBEKU, Laura H Mariani · 2019 to 2026
$12.1MNCATS NIH HHS U2C TR002818NCATS NIH HHS UL1 TR001873NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG006378NHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG006380NHGRI NIH HHS U01 HG006382NHGRI NIH HHS U01 HG006385NHGRI NIH HHS U01 HG006388NHGRI NIH HHS U01 HG006389NHGRI NIH HHS U01 HG006828NHGRI NIH HHS U01 HG006830NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U01 HG008664NHGRI NIH HHS U01 HG008666NHGRI NIH HHS U01 HG008672NHGRI NIH HHS U01 HG008673NHGRI NIH HHS U01 HG008676NHGRI NIH HHS U01 HG008679NHGRI NIH HHS U01 HG008680NHGRI NIH HHS U01 HG008684NHGRI NIH HHS U01 HG008685NHGRI NIH HHS U01 HG008701NHGRI NIH HHS U01 HG011166NHGRI NIH HHS U01 HG011167NHGRI NIH HHS U01 HG011169NHGRI NIH HHS U01 HG011172NHGRI NIH HHS U01 HG011175NHGRI NIH HHS U01 HG011176NHGRI NIH HHS U01 HG011181NHLBI NIH HHS R01 HL163854NIAID NIH HHS U01 AI152960NICHD NIH HHS R21 HD104176NIDDK NIH HHS K01 DK137031NIDDK NIH HHS K25 DK128563NIDDK NIH HHS R01 DK076683NIDDK NIH HHS R01 DK105124NIDDK NIH HHS R01 DK119380NIDDK NIH HHS R01 DK134347NIDDK NIH HHS R01 DK136765NIDDK NIH HHS RC2 DK116690NIDDK NIH HHS RC2 DK122397NIDDK NIH HHS U01 DK100876NIDDK NIH HHS U01 DK116066NIDDK NIH HHS U24 DK100845NIDDK NIH HHS U54 DK083912NINDS NIH HHS U01 NS041588NLM NIH HHS R01 LM013061
Abstract
African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
Indexed as
Glomerulosclerosis, Focal SegmentalApolipoprotein L1ApolipoproteinsGenetic Predisposition to DiseaseGenotypeHumansRisk FactorsAPOL1 protein, humanApolipoprotein L1Apolipoproteins
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