{
  "audit_date": "2026-07-11",
  "project": "IDSX",
  "sources_checked": ["local_5FQL.pdb", "IDS_P22304_Mutation_Structural_Database.xlsx", "UniProt_API_P22304", "UniProt_API_P04062", "ClinVar_eutils", "RCSB_5FQL"],
  "ids": {
    "uniprot": "P22304",
    "uniprot_id": "IDS_HUMAN",
    "protein_name": "Iduronate 2-sulfatase",
    "sequence_length": 550,
    "aa152": "S",
    "aa152_verified": true,
    "pdb": "5FQL",
    "pdb_title": "Insights into Hunter syndrome from the structure of iduronate-2-sulfatase",
    "resolution_A": 2.3,
    "method": "X-RAY DIFFRACTION",
    "residue_84_in_pdb": "ALS",
    "residue_84_note": "formylglycine (3-oxoalanine) catalytic nucleophile — consistent with UniProt active site 84"
  },
  "ser152_structure": {
    "present_in_5FQL": true,
    "rsa_pct_project": 0,
    "dist_to_catalytic_pocket_A_project": 10.27,
    "og_contacts_lt_3_5A": [
      {"partner": "Asp148 OD2", "distance_A": 2.53},
      {"partner": "Thr118 OG1", "distance_A": 2.85}
    ],
    "verdict": "PASS — local geometry matches project claims"
  },
  "ser152ile_clinvar": {
    "variation_id": "3255739",
    "accession": "VCV003255739",
    "hgvs_cdna": "NM_000202.8(IDS):c.455G>T",
    "hgvs_protein": "p.Ser152Ile",
    "germline_classification": "Pathogenic",
    "review_status": "criteria provided, single submitter",
    "last_evaluated": "2024-06-07",
    "project_note": "Project DB lists Pathogenic; ClinVar ID was empty on some rows — now filled by this audit. HGVS is c.455G>T not c.454A>T."
  },
  "database_integrity": {
    "mutation_master_n": 797,
    "position_152_annotation_rows": 5,
    "issues": [
      {
        "severity": "medium",
        "item": "Duplicate Ser152Arg rows in Structural_Annotation / Mutation_Master",
        "action": "deduplicate before publication tables"
      },
      {
        "severity": "medium",
        "item": "Some Pathogenic labels lack ClinVar_id in Excel",
        "action": "backfill ClinVar accessions (S152I → VCV003255739)"
      },
      {
        "severity": "low",
        "item": "c.454A>T row at position 152 with clin=None",
        "action": "verify DNA change mapping; do not equate to S152I without HGVS check"
      },
      {
        "severity": "info",
        "item": "is_catalytic_residue flag false for Arg88 despite dist_cat=2.77Å",
        "action": "expected if flag is strict catalytic set; Arg88 correctly lives in CAUTION_POCKET by distance rule"
      },
      {
        "severity": "info",
        "item": "Asp45 is_direct_Ca_ligand=true, dist_cat=1.33Å",
        "action": "consistent with Ca coordination; hard-exclude path OK"
      }
    ]
  },
  "gcase_reference": {
    "uniprot": "P04062",
    "uniprot_id": "GBA1_HUMAN",
    "gene": "GBA1",
    "protein_name": "Lysosomal acid glucosylceramidase",
    "length": 536,
    "chaperone_example": "ambroxol",
    "disease": "Gaucher disease / GBA1-PD",
    "role_in_IDSX": "success-condition reference only — not an IDS drug claim"
  },
  "overall": {
    "structure_core_claims": "VERIFIED",
    "uniprot_identity": "VERIFIED",
    "clinvar_S152I_pathogenic": "VERIFIED (single submitter)",
    "amenability_scores": "UNVERIFIED experimentally (by design — proxy)",
    "residual_activity_map": "MISSING — next work item"
  }
}