ArticleNature genetics2012
FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair.
Article in Nature genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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151 citing papers in PubMed, 238 citations in OpenAlex.
- Kidney organoids as models for hereditary kidney diseases: Toward precision medicine (Review).Experimental and therapeutic medicine · 2026Review
- Genetic kidney disease in adults-the pathologists' perspective.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- Dysregulation of the DNA repair‑immune axis: Targeted therapeutic strategies for autoimmune diseases (Review).International journal of molecular medicine · 2026Review
- Phenotype-Driven Next-Generation Sequencing and Structure-Based In Silico Analysis Reveal Disease-Specific Diagnostic Yield and Genotype-Phenotype Correlations in Inherited Kidney Diseases.Life (Basel, Switzerland) · 2026Article
- Article
- Transfer of Aging: Implications for Pediatric Solid Organ Transplantation.Pediatric transplantation · 2025Review
- Breast cancer gene-1 (BRCA1) potentiates maladaptive repair after kidney injury.The Journal of experimental medicine · 2025Article
- Structural and molecular basis of PCNA-activated FAN1 nuclease function in DNA repair.Nature communications · 2025Article
- FAN1-mediated translesion synthesis and POLQ/HELQ-mediated end joining generate interstrand crosslink-induced mutations.Nature communications · 2025Article
- Fanconi syndrome with karyomegalic interstitial nephritis after ifosfamide treatment for osteosarcoma: a case report.CEN case reports · 2025Article
- A porcine model of Fanconi anemia.PloS one · 2025Article
- Karyomegalic interstitial nephritis: A case series and review of the literature on genetic insights and clinical challenges.Clinical nephrology. Case studies · 2025Article
- The unexpected diagnosis of karyomegalic interstitial nephritis in a presumed case of Mesoamerican Nephropathy: a case report.Frontiers in medicine · 2025Article
- A rare multisystemic disorder with chronic kidney disease: Karyomegalic interstitial nephritis due to homozygous FAN1 c.2260C>T variant.Nephrology (Carlton, Vic.) · 2024Article
- A case of karyomegalic interstitial nephritis without FAN1 mutations in the setting of brentuximab, ifosfamide, and carboplatin exposure.BMC nephrology · 2024Article
- Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child.Oman medical journal · 2024Article
- Microsatellite break-induced replication generates highly mutagenized extrachromosomal circular DNAs.NAR cancer · 2024Article
- Phenotypic and Genotypic Features of theInternational journal of molecular sciences · 2024Article
- Posttranscriptional regulation ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- p53 regulates diverse tissue-specific outcomes to endogenous DNA damage in mice.Nature communications · 2024Article
91 more citing papers are in PubMed but not listed here.
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44 authors at 20 institutions in 8 countries.
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Abstract
Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.
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