{
 "meta": {
  "api_version": "1.0.0",
  "dataset_version": "2.0.1+unreleased",
  "live_matches_release": false,
  "archived_release": {
   "version": "2.0.1",
   "version_doi": "10.5281/zenodo.23090261",
   "date": "2026-10-01",
   "studies": 428
  },
  "data_fingerprint": "4823f516b720e66843f0b75952daf5ccc5279a7c20c0cb7c0d1ac126ff6ca768",
  "corpus_snapshot": "2026-10-24T21:34:23+0200",
  "source_commit": "8f0f14a10e115daab72bb59e5bf8c63eda1daeb8",
  "license": "CC-BY-4.0",
  "cite": "Barton O. Oliver's mTOR Atlas (live data, not an archived version; give corpus_snapshot and source_commit). doi:10.5281/zenodo.22059963",
  "docs": "https://mtor-atlas.org/api/"
 },
 "data": {
  "id": "FLCN-RAG",
  "claim": "FLCN / FNIP1/2 activates Rag GTPases",
  "source": {
   "name": "FLCN / FNIP1/2",
   "entity": "flcn-fnip1-2"
  },
  "target": {
   "name": "Rag GTPases",
   "entity": "rag-gtpases"
  },
  "effect": "activates",
  "type": "gap-activity",
  "directness": "direct",
  "timescale": "seconds",
  "compartment": "lyso",
  "map_band": "lyso",
  "species": [
   "human cells"
  ],
  "mechanism": "FLCN-FNIP is the GAP for RagC/D: it makes RagC/D hydrolyse its bound GTP, which puts that half of the Rag dimer into the GDP-bound state. 'Activates' on this edge means exactly that: FLCN-FNIP sets the nucleotide state of RagC/D. It does not switch on every Rag. The dimer can hold mTORC1 only when both halves are in the right state (RagA/B GTP-bound and RagC/D GDP-bound), and other factors act on the RagA/B half. Its direct effect is SUBSTRATE-SPECIFIC: it gates TFEB and TFE3 phosphorylation, while canonical outputs like S6K1 and 4E-BP1 largely carry on without it in the short term.",
  "mechanism_beginner": "FLCN helps set the other half of the Rag pair (RagC/D) into its working shape: it makes RagC/D break down its bound GTP, the cell's energy-carrying molecule. So 'activates' here means it sets the state of that one half, not that it switches on every Rag. Its direct job is mainly to control one group of outputs (TFEB and TFE3) rather than the whole pathway, but in kidney and lung, losing FLCN can still end up over-activating mTORC1 through a feedback loop.",
  "context": null,
  "boundary": "FLCN's direct effect is substrate-specific: losing it blocks mTORC1 phosphorylation of TFEB/TFE3 while leaving S6K1 and 4E-BP1 largely intact in the short term (NAP2020). That is not the whole of Birt-Hogg-Dube, though. Constitutively active TFEB/TFE3 drive a feedback loop that hyperactivates mTORC1, and in kidney and lung that mTORC1 hyperactivation is itself a key driver of cyst and tumour formation (Di Malta 2023, EMBO Mol Med, PMID 36987696; Ferniani 2026, FER2026 in corpus; Cao 2026, JCI, PMID 41697734, 3 BHD patient lungs + mouse). So the regulation is tissue- and time-dependent, not a flat absence of hyperactivation.",
  "boundary_tags": [],
  "note": "2026-10-10: beginner text still said FLCN 'only changes one specific output (TFEB), not the whole pathway', the overstatement that audit A02 corrected in the expert layer. Now matches the boundary: direct effect substrate-specific (TFEB/TFE3), feedback hyperactivation of mTORC1 in kidney and lung.",
  "consensus_contested": false,
  "curation_contested": false,
  "contested": false,
  "confidence": {
   "mechanistic": "high",
   "human_relevance": "plausible",
   "consensus": "established"
  },
  "evidence": {
   "kind": "Structural",
   "strongest": {
    "code": "M",
    "label": "Molecular — cells, biochemistry, structure"
   },
   "supporting": [
    "LAW2019",
    "SHE2019",
    "NAP2020"
   ],
   "conflicting": []
  },
  "external_refs": [
   {
    "pmid": "36987696",
    "cited_in": [
     "boundary"
    ],
    "in_corpus": false,
    "url": "https://pubmed.ncbi.nlm.nih.gov/36987696/"
   },
   {
    "pmid": "41697734",
    "cited_in": [
     "boundary"
    ],
    "in_corpus": false,
    "url": "https://pubmed.ncbi.nlm.nih.gov/41697734/"
   }
  ],
  "reviewed": null,
  "updated": null,
  "checked": null,
  "review_status": "unreviewed",
  "reviewer": null,
  "curation_status": "Proposed",
  "url": "https://mtor-atlas.org/relation/FLCN-RAG/",
  "api_url": "https://mtor-atlas.org/api/v1/relations/FLCN-RAG.json"
 }
}