{
  "abstract": "Pathogenic variants in human KCTD3 are associated with severe neurodevelopmental disorders characterized by early-onset seizures, developmental delay, hypotonia, and cerebellar hypoplasia, but the underlying mechanisms remain unclear. Here we show that KCTD3 regulates neuronal structural organization through DAAM1, a protein involved in actin cytoskeleton assembly. In Kctd3-deficient neurons, DAAM1 protein levels are reduced, the axon initial segment is abnormally organized, and neurite growth and growth cone morphology are impaired. These defects are rescued by DAAM1 overexpression. Systemic Kctd3 depletion also disrupts axon initial segment organization and motor axon innervation at neuromuscular junctions, leading to motor dysfunction and growth impairment in mice. These findings identify a KCTD3-DAAM1 pathway required for neuronal structural development and provide a framework for understanding how KCTD3 deficiency contributes to neurodevelopmental disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Brain Sciences, DGIST, Daegu, Republic of Korea",
    "Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea",
    "Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy",
    "U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, Genoa, Italy",
    "Genomics and Clinical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy",
    "Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy",
    "Telethon Institute of Genetics and Medicine, Pozzuoli, Italy",
    "Service de génétique, CHU Nantes, Nantes, France",
    "UMR1231 GAD, Inserm, Université Bourgogne-Franche Comté, Dijon, France",
    "CHU Dijon Bourgogne, Service de Génomique Médicale, Laboratoire de Biologie Médicale, Dijon, France",
    "University Children’s Hospital, Paracelsus Medical University (PMU), Salzburg, Austria",
    "Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea",
    "Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA",
    "Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, Republic of Korea",
    "Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea",
    "Department of Genomic Medicine, Seoul national University Hospital, Seoul, Republic of Korea",
    "Department of Pediatrics, Seoul national University College of Medicine, Seoul, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yeonsoo Oh",
      "orcid": "0009-0007-1281-6954"
    },
    {
      "affs": [
        1
      ],
      "name": "Youngha Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Hoyong Jin"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Marcello Scala",
      "orcid": "0000-0003-2194-7239"
    },
    {
      "affs": [
        4
      ],
      "name": "Valeria Capra"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Annalaura Torella"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Vincenzo Nigro",
      "orcid": "0000-0002-3378-5006"
    },
    {
      "affs": [
        7
      ],
      "name": "Bertrand Isidor"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Frédéric Tran Mau-Them",
      "orcid": "0000-0002-3795-9456"
    },
    {
      "affs": [
        10
      ],
      "name": "René G. Feichtinger"
    },
    {
      "affs": [
        10
      ],
      "name": "Johannes A. Mayr",
      "orcid": "0000-0001-6970-336X"
    },
    {
      "affs": [
        10
      ],
      "name": "Saskia B. Wortmann"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Hyeyoon Kim"
    },
    {
      "affs": [
        11,
        13,
        14
      ],
      "name": "Dohyun Han",
      "orcid": "0000-0002-0841-1598"
    },
    {
      "affs": [
        15
      ],
      "name": "Jin Sook Lee"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Jong-Hee Chae"
    },
    {
      "affs": [
        1
      ],
      "name": "Murim Choi",
      "orcid": "0000-0002-9195-1455"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongcheol Cho",
      "orcid": "0000-0003-2356-7125"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5q7qd3qk61g96.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-10584-3",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13720015/",
  "id": "5q7qd3qk61g96",
  "issns": [
    "2399-3642"
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  "landing_url": "https://doi.org/10.1038/s42003-026-10584-3",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
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  "openalex": "W7167501527",
  "pdf_url": "https://www.nature.com/articles/s42003-026-10584-3_reference.pdf",
  "pmcid": "PMC13720015",
  "pmid": "42410234",
  "published": "2026-07-07",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/5q7qd3qk61g96.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:23:52Z",
      "native_id": "PMC13720015",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s42003-026-10584-3"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "KCTD3 deficiency disrupts axon initial segment organization and neurite outgrowth in a neurodevelopmental disorder mouse model",
  "title_text": "KCTD3 deficiency disrupts axon initial segment organization and neurite outgrowth in a neurodevelopmental disorder mouse model",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:00Z",
  "url": "https://research.draconitic.com/paper/5q7qd3qk61g96",
  "venue": "Communications Biology",
  "versions": []
}