{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in zebrafish and mice have identified TMEM161B as a critical modulator of cardiac rhythm. Loss‐of‐function mutations in this gene lead to arrhythmogenic phenotypes, characterized by arrhythmic calcium oscillations, impaired action potential repolarization, and dysregulated Ca²⁺ and K⁺ currents in cardiomyocytes. These findings establish TMEM161B as an essential regulator of cardiac electrophysiology, with potential implications for heritable arrhythmia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nParallel research has revealed a pivotal role for TMEM161B in neurodevelopment. Disruptions in TMEM161B function impair Sonic hedgehog (Shh) signaling, compromise primary cilium integrity, and disturb radial glial cell polarity and actin filopodia dynamics. Such defects have been linked to severe cortical malformations—including polymicrogyria, holoprosencephaly, and abnormal midline cleavage—in patient-derived brain organoids and animal models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies highlight the conserved and multifaceted role of TMEM161B across species. Beyond its impact on cardiac rhythm and cortical development, TMEM161B is implicated in the regulation of intracellular calcium handling—linking its modulation of ion channel activity with proper morphogenesis in a range of tissues. These integrative insights advance our understanding of how TMEM161B dysfunction may underlie diverse congenital heart and brain malformations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Charlotte D Koopman, Jessica De Angelis, Swati P Iyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The zebrafish "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "grime"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutant uncovers an evolutionarily conserved role for Tmem161b in the control of cardiac rhythm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2018220118"}], "href": "https://doi.org/10.1073/pnas.2018220118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33597309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33597309"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lu Wang, Caleb Heffner, Keng Ioi Vong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM161B modulates radial glial scaffolding in neocortical development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2209983120"}], "href": "https://doi.org/10.1073/pnas.2209983120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36669109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36669109"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shyam K Akula, Jack H Marciano, Youngshin Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2209964120"}], "href": "https://doi.org/10.1073/pnas.2209964120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36669111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36669111"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kelly A Smith, Nicole Dominado, Jessica F Briffa "}, {"type": "b", "children": [{"type": "t", "text": "Fins, fur, and wings: the study of Tmem161b across species, and what it tells us about its function in the heart."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mamm Genome (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00335-023-09994-z"}], "href": "https://doi.org/10.1007/s00335-023-09994-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37222785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37222785"}]}]}]}