{
 "gene": "KRAS",
 "run_date": "2026-06-10T02:59:49",
 "timeline": {
  "current_model": "KRAS encodes a membrane-associated small GTPase that cycles between inactive GDP-bound and active GTP-bound states regulated by GEFs and GAPs; oncogenic mutations (G12, G13, Q61) impair GAP-stimulated GTP hydrolysis (with G13D retaining neurofibromin-sensitivity), driving constitutive activation of RAF/MEK/ERK and PI3K/AKT downstream signaling; K-Ras4B requires farnesylation and polybasic HVR for plasma membrane localization, undergoes dynamic membrane association regulated by calmodulin (which extracts it from the membrane) and PDE\u03b4, is phosphorylated at Ser181 by PKC (antagonized by CaM) to reduce GAP sensitivity and modulate signaling, and can dimerize via the \u03b14-\u03b15 interface in a manner that influences MEK inhibitor sensitivity and oncogenic activity; its rare codon enrichment limits protein expression compared to HRAS, and KRAS-driven transcription operates predominantly through ERK to deregulate the APC/C and cell cycle machinery."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0003924",
     "term_label": "GTPase activity",
     "supporting_discovery_ids": [
      3,
      4
     ]
    },
    {
     "term_id": "GO:0140110",
     "term_label": "transcription regulator activity",
     "supporting_discovery_ids": [
      18
     ]
    },
    {
     "term_id": "GO:0008289",
     "term_label": "lipid binding",
     "supporting_discovery_ids": [
      15,
      21
     ]
    },
    {
     "term_id": "GO:0060089",
     "term_label": "molecular transducer activity",
     "supporting_discovery_ids": [
      4,
      18
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005886",
     "term_label": "plasma membrane",
     "supporting_discovery_ids": [
      10,
      13,
      14
     ]
    },
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      9,
      14
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-162582",
     "term_label": "Signal Transduction",
     "supporting_discovery_ids": [
      18,
      20
     ]
    },
    {
     "term_id": "R-HSA-1643685",
     "term_label": "Disease",
     "supporting_discovery_ids": [
      23,
      25
     ]
    },
    {
     "term_id": "R-HSA-1640170",
     "term_label": "Cell Cycle",
     "supporting_discovery_ids": [
      18
     ]
    },
    {
     "term_id": "R-HSA-1266738",
     "term_label": "Developmental Biology",
     "supporting_discovery_ids": [
      17
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "NF1",
    "CALM1",
    "PDE6D",
    "RAF1",
    "PRKC",
    "VHL"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P01116",
   "full_name": "GTPase KRas"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 8,
  "faith_total": 8,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.462673
 }
}