{
 "gene": "GSK3B",
 "run_date": "2026-06-10T01:55:21",
 "timeline": {
  "current_model": "GSK3B is a constitutively active serine/threonine kinase (inactivated by Ser9 phosphorylation by AKT, activated at Tyr216) that phosphorylates a broad range of substrates including Tau (at S199, T205, T231, S396, S404, promoting neurofibrillary tangle formation), 53BP1 (at T334, directing DNA double-strand break repair from NHEJ toward homologous recombination), MCL1 (triggering FBXW7-mediated ubiquitination and degradation to induce axonal autophagy), CRMP2 (driving microtubule reorganization in Wallerian degeneration downstream of the ZNRF1-AKT-GSK3B axis), BCL2 (at Ser70, promoting its ubiquitination and autophagy), TRAF6 (at Thr266, causing its K48-ubiquitination and degradation), and ULK1 (at S405/S415, activating autophagy initiation); GSK3B activity is regulated by Wnt/\u03b2-catenin signaling, PI3K/AKT, PP2A, PREP, and lithium (which both directly inhibits kinase activity and reduces GSK3B mRNA in hippocampal neurons), and its nuclear localization is linked to pro-apoptotic function in oligodendrocytes, while its loss-of-function causes neurodevelopmental disorders including autism spectrum disorder with dendritic and spine maturation defects."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140096",
     "term_label": "catalytic activity, acting on a protein",
     "supporting_discovery_ids": [
      0,
      1,
      2,
      4,
      6,
      8
     ]
    },
    {
     "term_id": "GO:0016740",
     "term_label": "transferase activity",
     "supporting_discovery_ids": [
      2,
      6,
      8,
      16
     ]
    },
    {
     "term_id": "GO:0140097",
     "term_label": "catalytic activity, acting on DNA",
     "supporting_discovery_ids": [
      8
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005634",
     "term_label": "nucleus",
     "supporting_discovery_ids": [
      8,
      11
     ]
    },
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      0,
      1
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-9612973",
     "term_label": "Autophagy",
     "supporting_discovery_ids": [
      1,
      2,
      3,
      12
     ]
    },
    {
     "term_id": "R-HSA-73894",
     "term_label": "DNA Repair",
     "supporting_discovery_ids": [
      8
     ]
    },
    {
     "term_id": "R-HSA-5357801",
     "term_label": "Programmed Cell Death",
     "supporting_discovery_ids": [
      5,
      11,
      18
     ]
    },
    {
     "term_id": "R-HSA-162582",
     "term_label": "Signal Transduction",
     "supporting_discovery_ids": [
      0,
      3,
      15,
      18
     ]
    },
    {
     "term_id": "R-HSA-1266738",
     "term_label": "Developmental Biology",
     "supporting_discovery_ids": [
      22
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "MCL1",
    "ULK1",
    "BCL2",
    "TRAF6",
    "53BP1",
    "CRMP2",
    "DNMT1",
    "TFR1"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P49841",
   "full_name": "Glycogen synthase kinase-3 beta"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 6,
  "faith_total": 6,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.225746
 }
}