{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ANKS6 is emerging as a central mediator within ciliary signaling networks that are essential for kidney development and function. It localizes to the proximal region of the primary cilium—particularly within the inversin compartment—where it forms a molecular bridge connecting key proteins such as NEK8, INVS, and NPHP3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and helps organize higher order protein assemblies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Critical to its function is the sterile α motif (SAM) domain, which mediates interactions with proteins including ANKS3 and BICC1. Mutations affecting this domain (e.g., the R823W or I747N substitutions) destabilize these interactions, disrupt ciliary architecture, and lead to cystic kidney phenotypes in both animal models and human patients."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, ANKS6 plays a regulatory role in modulating intracellular signaling pathways; its deficiency or mutation has been associated with altered Hippo and canonical Wnt signaling, contributing not only to renal cystogenesis but also to extrarenal manifestations such as laterality defects and bile duct malformations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Recent findings further suggest that ANKS6 may participate in RNA binding and stress responses through association with stress granules alongside other nephronophthisis (NPHP) proteins"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", underscoring its multifaceted role in maintaining cellular homeostasis. Finally, in vivo studies using transgenic rat models overexpressing mutant ANKS6 provide direct evidence linking its dysfunction to polycystic kidney disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies highlight ANKS6 as a critical scaffold and signaling regulator whose proper function is essential for ciliary integrity and kidney morphogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sylvia Hoff, Jan Halbritter, Daniel Epting, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2681"}], "href": "https://doi.org/10.1038/ng.2681"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23793029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23793029"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Henrietta W Bennett, Anna-Karin Gustavsson, Camille A Bayas, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The SAM domain of ANKS6 has different interacting partners and mutations can induce different cystic phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ki.2015.122"}], "href": "https://doi.org/10.1038/ki.2015.122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26039630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26039630"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wei Kan, Fengqin Fang, Lin Chen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Loss of Anks6 leads to YAP deficiency and liver abnormalities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddaa197"}], "href": "https://doi.org/10.1093/hmg/ddaa197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32886109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32886109"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hannah Schwarz, Bernt Popp, Rannar Airik, et al. 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