{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AHI1 encodes “Jouberin,” a multidomain protein characterized by multiple WD40‐repeat motifs and an SH3 domain that plays key roles in development and cellular homeostasis. In the nervous system, AHI1 is highly expressed in specific neuronal populations and is essential for proper cerebellar and cortical development. Mutations in this gene disrupt normal mid‐hindbrain patterning and axonal decussation, giving rise to Joubert syndrome and related neurological phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the retina, loss of AHI1 function impairs photoreceptor outer segment formation and proper opsin trafficking, leading to early photoreceptor degeneration; moreover, its dosage can modify the severity of retinal involvement in ciliopathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " At the cellular level, AHI1 localizes predominantly to the mother centriole and directly interacts with Rab8a to promote ciliogenesis and appropriate vesicular trafficking, thereby ensuring the assembly and maintenance of primary cilia and efficient ciliary signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, AHI1 mutations and variants have been implicated as genetic modifiers that influence not only the neurological but also the renal phenotypes seen in ciliopathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Beyond its central role in ciliogenesis and neurodevelopment, common variation at the AHI1 locus has been associated with neuropsychiatric disorders such as schizophrenia and autism spectrum disorders"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while its deregulated expression in hematopoietic cells potentiates oncogenic networks in chronic myeloid leukemia by promoting BCR‐ABL and JAK2–STAT5 signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, locus‐wide association studies have linked the AHI1 region with susceptibility to type 2 diabetes, suggesting pleiotropic roles for this gene in diverse human diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Russell J Ferland, Wafaa Eyaid, Randall V Collura, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/425985"}], "href": "https://doi.org/10.1086/425985"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15467982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15467982"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Carrie M Louie, Gianluca Caridi, Vanda S Lopes, et al. 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