ArticleProceedings of the National Academy of Sciences of the United States of America2014
Evolution of the primate trypanolytic factor APOL1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection.Communications biology · 2021Pooled it
- Genome-wide association study for time to failure of kidney transplants from African American deceased donors.Clinical transplantation · 2020Pooled it
- 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
- An integrative review of APOL1 kidney disease with a focus on the Brazilian population.Clinics (Sao Paulo, Brazil) · 2026Review
- When Cure Meets Susceptibility: APOL1 -Associated Kidney Injury After Gene Therapy for Sickle Cell Disease.American journal of hematology · 2026Article
- APOL1 risk alleles modulate T cell receptor signaling to promote allograft rejection.The Journal of clinical investigation · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Germline-targeted baboon apolipoprotein L-1 protects mice against African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular Mechanisms of APOL1-Associated Kidney Disease.International journal of molecular sciences · 2026Review
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- A novelRenal failure · 2025Article
- APOL1 risk variants induce metabolic reprogramming of podocytes in patient-derived kidney organoids.Stem cell reports · 2025Article
- Missense Variants in Nutrition-Related Genes: A Computational Study.International journal of molecular sciences · 2025Article
- De novo rates of aProceedings of the National Academy of Sciences of the United States of America · 2025Article
- G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway.bioRxiv : the preprint server for biology · 2025Article
- The APOL1 p.N264K variant is co-inherited with the G2 kidney disease risk variant through a proximity recombination event.G3 (Bethesda, Md.) · 2025Article
- APOL1 Dynamics in Diabetic Kidney Disease and Hypertension.Biomolecules · 2025Review
- Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.Nature communications · 2025Article
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 11 institutions in 4 countries.
Funding
Abstract
ApolipoproteinL1 (APOL1) protects humans and some primates against several African trypanosomes. APOL1 genetic variants strongly associated with kidney disease in African Americans have additional trypanolytic activity against Trypanosoma brucei rhodesiense, the cause of acute African sleeping sickness. We combined genetic, physiological, and biochemical studies to explore coevolution between the APOL1 gene and trypanosomes. We analyzed the APOL1 sequence in modern and archaic humans and baboons along with geographic distribution in present day Africa to understand how the kidney risk variants evolved. Then, we tested Old World monkey, human, and engineered APOL1 variants for their ability to kill human infective trypanosomes in vivo to identify the molecular mechanism whereby human trypanolytic APOL1 variants evade T. brucei rhodesiense virulence factor serum resistance-associated protein (SRA). For one APOL1 kidney risk variant, a two-residue deletion of amino acids 388 and 389 causes a shift in a single lysine residue that mimics the Old World monkey sequence, which augments trypanolytic activity by preventing SRA binding. A second human APOL1 kidney risk allele, with an amino acid substitution that also restores sequence alignment with Old World monkeys, protected against T. brucei rhodesiense due in part to reduced SRA binding. Both APOL1 risk variants induced tissue injury in murine livers, the site of transgenic gene expression. Our study shows that both genetic variants of human APOL1 that protect against T. brucei rhodesiense have recapitulated molecular signatures found in Old World monkeys and raises the possibility that APOL1 variants have broader innate immune activity that extends beyond trypanosomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.