The APOL1 variant p.N264K is predicted to block ion flow by occluding a pore at the cell surface - PubMed
14 hours ago
- #Kidney Disease
- #Molecular Dynamics
- #APOL1
- The APOL1 gene variants G1 and G2 are linked to increased risk of APOL1-mediated kidney disease.
- A protective variant, p.N264K (M1), reduces renal damage risk by eliminating APOL1-G2's cytotoxicity.
- Both cytotoxic G2 and nontoxic M1-G2 show similar intracellular localization, surface expression, and turnover kinetics.
- N-glycosylation assays and 3D models indicate no differences in topology; both span the membrane four times, forming a potential ion channel.
- Molecular dynamics analyses suggest lysine at position 264 in M1 occludes the channel, preventing ion pore activity.
- The C-terminal region may contribute to APOL1 multimerization, influencing ion flux and cytotoxicity.