{
 "gene": "PLD3",
 "run_date": "2026-06-10T06:43:35",
 "timeline": {
  "current_model": "PLD3 is a type II transmembrane lysosomal protein that functions as a 5'-to-3' single-stranded DNA and RNA exonuclease (degrading TLR7/TLR9 ligands to prevent autoinflammation), synthesizes the critical lysosomal phospholipid S,S-BMP via glycerol stereo-inversion, and undergoes sequential post-translational modifications (N-glycosylation, AMPylation by FICD, and proteolytic cleavage) that regulate its activation; its loss or disease-associated variants (e.g., V232M) impair nuclease and phospholipase activities, disrupt endolysosomal biogenesis in neurons, cause axonal spheroid accumulation with conduction blockade, and dysregulate innate immune nucleic-acid sensing through both endosomal TLR and STING pathways."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140098",
     "term_label": "catalytic activity, acting on RNA",
     "supporting_discovery_ids": [
      0,
      1,
      4,
      6,
      17
     ]
    },
    {
     "term_id": "GO:0140097",
     "term_label": "catalytic activity, acting on DNA",
     "supporting_discovery_ids": [
      0,
      4,
      6
     ]
    },
    {
     "term_id": "GO:0016787",
     "term_label": "hydrolase activity",
     "supporting_discovery_ids": [
      0,
      2,
      4,
      6,
      8
     ]
    },
    {
     "term_id": "GO:0003677",
     "term_label": "DNA binding",
     "supporting_discovery_ids": [
      3,
      4,
      6
     ]
    },
    {
     "term_id": "GO:0003723",
     "term_label": "RNA binding",
     "supporting_discovery_ids": [
      1,
      17
     ]
    },
    {
     "term_id": "GO:0016740",
     "term_label": "transferase activity",
     "supporting_discovery_ids": [
      2
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005764",
     "term_label": "lysosome",
     "supporting_discovery_ids": [
      0,
      6,
      8,
      11,
      16
     ]
    },
    {
     "term_id": "GO:0005768",
     "term_label": "endosome",
     "supporting_discovery_ids": [
      10
     ]
    },
    {
     "term_id": "GO:0005783",
     "term_label": "endoplasmic reticulum",
     "supporting_discovery_ids": [
      9
     ]
    },
    {
     "term_id": "GO:0005886",
     "term_label": "plasma membrane",
     "supporting_discovery_ids": [
      9
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-168256",
     "term_label": "Immune System",
     "supporting_discovery_ids": [
      0,
      1,
      18
     ]
    },
    {
     "term_id": "R-HSA-1430728",
     "term_label": "Metabolism",
     "supporting_discovery_ids": [
      2
     ]
    },
    {
     "term_id": "R-HSA-8953854",
     "term_label": "Metabolism of RNA",
     "supporting_discovery_ids": [
      1,
      17
     ]
    },
    {
     "term_id": "R-HSA-1643685",
     "term_label": "Disease",
     "supporting_discovery_ids": [
      2,
      8,
      12
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "PLD4",
    "FICD",
    "PGRN",
    "CDK1",
    "APP",
    "SORL1"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "Q8IV08",
   "full_name": "5'-3' exonuclease PLD3"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 8,
  "faith_total": 8,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.168844
 }
}