biostudies-literatureHung AMNCATS NIH HHSNIDDK NIH HHSCSRD VA1889-1899https://www.ebi.ac.uk/biostudies/studies/S-EPMC10631602biostudies-literatureUnknown34(11)<h4>Significance statement</h4>African Americans are at increased risk of CKD in part due to high-risk (HR) variants in the apolipoprotein L1 ( APOL1 ) gene, termed G1/G2. A different APOL1 variant, p.N264K , reduced the risk of CKD and ESKD among carriers of APOL1 HR variants to levels comparable with individuals with APOL1 low-risk variants in an analysis of 121,492 participants of African ancestry from the Million Veteran Program (MVP). Functional genetic studies in cell models showed that APOL1 p.N264K blocked APOL1 pore-forming function and ion channel conduction and reduced toxicity of APOL1 HR mutations. Pharmacologic inhibitors that mimic this mutation blocking APOL1 -mediated pore formation may be able to prevent and/or treat APOL1 -associated kidney disease.<h4>Background</h4>AfrJournal of the American Society of Nephrology : JASNGenetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease.PMC10631602UL1 TR002243IK2 CX002452T32 DK007569R01 DK122075I01 CX001897IK2 CX002027Wilson PIruvanti PTriozzi JLEstrada KWhitbourne SBGappy SWilson OGreen EMJhala DGress TWChen HCRobinson-Cohen CArgyres DPConnor TGutierrez SKinlay SLiang PAguayo SAssimon VAChan HNorton JPoon SGodschalk MTsao PPalacio AMoser JDuVall SLDellitalia LBrewer JVOkusaga OXu JHauser EKranzler HShah SCChurby LAhuja SShayan SABallas ZMoorman JHung AMPotter EWhooley MHarley JLiangpunsakul SLichy JWilliams AELuoh SWAndroulakis XMHammer KDeen JEKilbourne ATandon NYu ZServatius RGupta SFaulk LCBalasubramanian PKlein JSriram PGreco JMurdoch MAssimes TMahan CSCohen DSiew EDMatheny MStephens BBeckham JWells JMillion Veteran ProgramBoyko EOslin DVillareal GMozaffari SVTsao PSSharma SMastorides SBrophy MTWallbom AMeyer PGesek FWheless LJacono FMack THurley RFujii DLandry MMatheny MESusztak KHung AWhittle JMates EMuralidhar SAlexander KPyarajan SChandrasekar SHoek MCho KVlasschaert CSelva LEYeh SSFayad JHamner MWalsh JStrollo PRauchman MMattocks KOursler KASmith RMorgan TBhushan STao RGaziano JMBick AGGraham RRMarrache RThompson TChung CPfalseGenetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease.<h4>Significance statement</h4>African Americans are at increased risk of CKD in part due to high-risk (HR) variants in the apolipoprotein L1 ( APOL1 ) gene, termed G1/G2. A different APOL1 variant, p.N264K , reduced the risk of CKD and ESKD among carriers of APOL1 HR variants to levels comparable with individuals with APOL1 low-risk variants in an analysis of 121,492 participants of African ancestry from the Million Veteran Program (MVP). Functional genetic studies in cell models showed that APOL1 p.N264K blocked APOL1 pore-forming function and ion channel conduction and reduced toxicity of APOL1 HR mutations. Pharmacologic inhibitors that mimic this mutation blocking APOL1 -mediated pore formation may be able to prevent and/or treat APOL1 -associated kidney disease.<h4>Background</h4>Afr2023-01-01T00:00:00Z2023 Nov2026-06-08T06:28:05.18Z2026-06-08T03:14:24.558ZS-EPMC106316023779882210.1681/ASN.0000000000000219