ArticleAmerican journal of human genetics2022
Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- From Guidelines to Practice: Pilot Implementation and Analytical Boundaries of a Focused ADPKD-Spectrum Gene Panel.Diagnostics (Basel, Switzerland) · 2026Article
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- Bridging structure and function: artificial intelligence-based modelling of kidney proteins.Nature reviews. Nephrology · 2026Review
- Monogenic Etiologies of Kidney Cysts in the Pediatric Population: An Observational Cohort Study.Clinical journal of the American Society of Nephrology : CJASN · 2026Observational
- A Ciliary Phosphoinositide Pathway Regulates the Dosage of Polycystins in Primary Cilia.Journal of the American Society of Nephrology : JASN · 2026Article
- Genomic and epigenomic landscape of ADPKD: towards precision diagnostics and tailored treatments.Frontiers in epigenetics and epigenomics · 2026Review
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- Autosomal dominant polycystic kidney disease: an overview of recent genetic and clinical advances.Renal failure · 2025Review
- Genetic testing in autosomal dominant polycystic kidney disease: why it matters in 2025.Clinical kidney journal · 2025Article
- Antiproliferative effects of dihydrotanshinone I on autosomal dominant polycystic kidney disease via immunomodulation.The Journal of pharmacology and experimental therapeutics · 2025Article
- Glycosylation in kidney diseases.Precision clinical medicine · 2025Review
- Using Large Genomic Biobanks to Generate Insights into Genetic Kidney Disease.Seminars in nephrology · 2025Review
- The impact of a secondary, rare, non-pathogenic PKD1 variant on disease progression in autosomal dominant polycystic kidney disease.Journal of nephrology · 2025Article
- Characterization of the Cystic Phenotype Associated with Monoallelic ALG8 and ALG9 Pathogenic Variants.Journal of the American Society of Nephrology : JASN · 2025Article
- Review
- Review
- Transcription factor SMAD5 upregulates ALG5 to alleviate osteoporosis development by inducing osteogenic differentiation.Journal of orthopaedics · 2025Article
- Extrarenal manifestations in inherited kidney diseases.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- An intronic micro-deletion impacts the transcription and translation ofFrontiers in genetics · 2025Article
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Authors and funding
26 authors at 16 institutions in 3 countries.
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Abstract
Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. Genetic testing remains inconclusive in ∼7% of the families. We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. Four additional families with pathogenic variants in ALG5 were identified. Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline.
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