ArticleAmerican journal of human genetics2020
DAAM2 Variants Cause Nephrotic Syndrome via Actin Dysregulation.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Functional characterization of genetic variants associated with rare inherited renal disorders in the Sri Lankan population.Molecular genetics and genomics : MGG · 2026Article
- Disheveled associated activator of morphogenesis 2 variants may produce alport-like changes: a case report.Molecular cytogenetics · 2026Article
- Article
- Emerging genetic mechanisms of glomerular proteinuria: a podocyte-centered multi-layer network perspective.Frontiers in genetics · 2026Review
- Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment.Nature communications · 2025Article
- Mechanisms of podocyte injury in genetic kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- Case Report: a novel variant inFrontiers in nephrology · 2025Article
- The dishevelled associated activator of morphogenesis protein 2 (Daam2) regulates neural tube closure.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Sex-specific molecular signature of mouse podocytes in homeostasis and in response to pharmacological challenge with rapamycin.Biology of sex differences · 2024Article
- Altered Endoplasmic Reticulum Integrity and Organelle Interactions in Living Cells Expressing INF2 Variants.International journal of molecular sciences · 2024Article
- Assessing the contribution of genes involved in monogenic bone disorders to the etiology of atypical femoral fractures.Human genomics · 2024Article
- Purine-Rich Element Binding Protein Alpha, a Nuclear Matrix Protein, Has a Role in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- RNAseq of INOCA patients identifies innate, invariant, and acquired immune changes: potential autoimmune microvascular dysfunction.Frontiers in cardiovascular medicine · 2024Article
- The prognostic value of DAAM2 in lower grade glioma, liver cancer, and breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Article
- Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Podocyte Endocytosis in Regulating the Glomerular Filtration Barrier.Frontiers in medicine · 2022Review
- Formins in Human Disease.Cells · 2021Review
- Review
- Increased dishevelled associated activator of morphogenesis 2, a new podocyte-associated protein, in diabetic nephropathy.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Article
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Authors and funding
33 authors at 11 institutions in 4 countries.
Funding
Abstract
The discovery of >60 monogenic causes of nephrotic syndrome (NS) has revealed a central role for the actin regulators RhoA/Rac1/Cdc42 and their effectors, including the formin INF2. By whole-exome sequencing (WES), we here discovered bi-allelic variants in the formin DAAM2 in four unrelated families with steroid-resistant NS. We show that DAAM2 localizes to the cytoplasm in podocytes and in kidney sections. Further, the variants impair DAAM2-dependent actin remodeling processes: wild-type DAAM2 cDNA, but not cDNA representing missense variants found in individuals with NS, rescued reduced podocyte migration rate (PMR) and restored reduced filopodia formation in shRNA-induced DAAM2-knockdown podocytes. Filopodia restoration was also induced by the formin-activating molecule IMM-01. DAAM2 also co-localizes and co-immunoprecipitates with INF2, which is intriguing since variants in both formins cause NS. Using in vitro bulk and TIRF microscopy assays, we find that DAAM2 variants alter actin assembly activities of the formin. In a Xenopus daam2-CRISPR knockout model, we demonstrate actin dysregulation in vivo and glomerular maldevelopment that is rescued by WT-DAAM2 mRNA. We conclude that DAAM2 variants are a likely cause of monogenic human SRNS due to actin dysregulation in podocytes. Further, we provide evidence that DAAM2-associated SRNS may be amenable to treatment using actin regulating compounds.
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