{
  "abstract": "Distinct protein features of pathogenic variants are illustrated here for a gene with an extraordinarily wide range of neurological syndromes: ATP1A3, the neuronal Na,K-ATPase. Vulnerable structure features produce mechanistically different consequences, from loss or gain of function to maladaptive cell biological responses. Variants in specific structural elements (glycines, prolines, and {beta}-sheets) link severe phenotype to impaired folding during biosynthesis. In contrast, impaired protein-protein interactions may result in brain malformation. Defective RNA transcripts, on the other hand, exhibit a range of benign to severe phenotypes, likely due to efficacy variability in the defensive degradation of aberrant mRNA and protein. Variant interpretation will benefit from understanding structure-specific vulnerabilities.",
  "abstract_shown": true,
  "affiliations": [
    "Mass General Hospital"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "K. J. Sweadner"
    },
    {
      "name": "L. J. Ozelius"
    },
    {
      "name": "A. Domingo"
    },
    {
      "name": "K. Mangkalaphiban"
    },
    {
      "name": "I. U. Haq"
    },
    {
      "name": "A. Brashear"
    },
    {
      "name": "E. Arystarkhova"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dzqzrgktacm93.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.13.758912",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758912v1.full",
  "id": "dzqzrgktacm93",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758912v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "1311|Genomics and Rare Diseases"
    ]
  ],
  "openalex": "W7222108403",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758912v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dzqzrgktacm93.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:58Z",
      "native_id": "10.64898/2026.10.13.758912",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758912v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "What is pathogenicity? Structural vulnerabilities lead to distinct phenotypes in a membrane protein, ATP1A3",
  "title_text": "What is pathogenicity? Structural vulnerabilities lead to distinct phenotypes in a membrane protein, ATP1A3",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:58Z",
  "url": "https://research.draconitic.com/paper/dzqzrgktacm93",
  "venue": "bioRxiv",
  "versions": []
}