{
  "id": 8980269,
  "title": "A bipolar disorder-associated ultra-rare AKAP11 protein-truncating variant attenuates stimulus-dependent PKA activation and induces anxiety- and depression-related behaviors in mice",
  "url": "https://urgent.news/2026/09/21/a-bipolar-disorder-associated-ultra-rare-akap11-protein-truncating",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-21T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752887v1?rss=1"
  },
  "original_language": "en",
  "account": "An ultra-rare genetic variant linked to bipolar disorder and schizophrenia has been linked to changes in a protein called AKAP11, which plays a role in regulating the activity of a key enzyme called PKA. This AKAP11 protein variant, known as a protein-truncating variant (PTV), was identified in a patient with bipolar disorder and introduced into mice through genome editing. The PTV reduced the levels of AKAP11 protein in mice, leading to a condition called haploinsufficiency, where only one copy of the gene is sufficient to produce the desired effect. Male mice with this PTV exhibited behavioral changes similar to anxiety and depression. Further analysis revealed that the PTV altered the levels of specific PKA regulatory and catalytic subunits in the mouse brain, reduced PKA phosphorylation of its target proteins, and impaired the development of new dendrites in the brain. These findings provide a genetically precise model of how ultra-rare AKAP11 PTVs may contribute to psychiatric disorders and offer a platform for investigating potential therapies.",
  "summary": "Rare genetic variants associated with psychiatric disorders are thought to have larger individual effect sizes and direct biological roles, offering a unique opportunity for understanding causal relationships between genetic architecture and disease phenotypes. A recent whole-exome sequencing meta-analysis identified an increased burden of ultra-rare protein-truncating variants (PTVs) in AKAP11…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}