Intrinsic and Innate Immunity Defect IEIs (IUIS Table 6)

name: Intrinsic and Innate Immunity Defect IEIs
display_name: Intrinsic and Innate Immunity Defect IEIs (IUIS Table 6)
creation_date: "2026-08-20T00:00:00Z"
description: >-
  IUIS Table 6 — defects in intrinsic and innate immunity. These inborn errors
  of immunity leave the adaptive compartment broadly intact and instead break a
  pattern-recognition, cytokine-signalling, or cell-intrinsic antimicrobial
  circuit. Their defining feature is narrow susceptibility: a single pathogen
  class — Candida, mycobacteria, herpesviruses, papillomavirus, invasive
  pyogenic bacteria — rather than the broad infection burden of combined or
  antibody deficiency.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the IUIS Table 6 pattern: a lesion in intrinsic or innate immunity
  producing pathogen-restricted, rather than general, infection susceptibility.
  Members are kept as separate Disease entries because the broken circuit and
  the pathogen it admits differ — the IL-17 axis and Candida in chronic
  mucocutaneous candidiasis, NK-cell development and herpesviruses in MCM10
  deficiency. The grouping is the natural home for the KB's Mendelian
  susceptibility entries, and it is what makes "narrow susceptibility" queryable
  as a class rather than restated per entry. No MONDO mapping: MONDO has no
  grouping class corresponding to IUIS Table 6, and the nearest candidates
  (e.g. immunodeficiency by pathogen) subsume only individual subtables.
membership_criteria:
- description: >-
    A disorder belongs to IUIS Table 6 if it is an inborn error of immunity
    whose primary lesion is in intrinsic or innate immunity — pattern
    recognition, innate cytokine signalling, or a cell-intrinsic antimicrobial
    program — typically producing susceptibility restricted to one pathogen
    class.
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: HAS_CLASSIFICATION
    classification: "iuis_category:innate immunity defect"
    description: >-
      Assigned to IUIS Table 6 (defects in intrinsic and innate immunity) via
      classifications.iuis_category on the member Disease entry. Stated in the
      keyed `<slot>:<value>` form so the audit reads the structured
      classifications block.
members:
- member: Chronic Mucocutaneous Candidiasis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Not one gene's disease but a convergent phenotype: every established
      etiology lies somewhere on the IL-17 circuit — the cytokine (IL17F), its
      receptor chains (IL17RA, IL17RC), the receptor-proximal adaptor
      (ACT1/TRAF3IP2), the Th17 master transcription factor (RORC), or STAT1
      gain of function repressing Th17 development. The clearest demonstration
      of the Table 6 logic that one circuit guards one pathogen class, here
      Candida at skin and mucosa.
    gene:
      preferred_term: STAT1
      term:
        id: hgnc:11362
        label: STAT1
- member: Immunodeficiency 80 with or without Congenital Cardiomyopathy
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Biallelic variants in MCM10, an essential activator of the CMG DNA
      replicative helicase, produce a profound natural killer cell deficiency
      with absent terminally mature NK cells. Where the other member here loses
      a cytokine circuit, this one loses an innate effector lineage outright
      through a defect in general DNA replication that the NK compartment is
      unusually sensitive to.
    gene:
      preferred_term: MCM10
      term:
        id: hgnc:18043
        label: MCM10
notes: >-
  Created 2026-08-20 to give the IUIS Table 6 disorders a place in the Inborn
  Errors of Immunity tree; both members already carried
  `classifications.iuis_category: innate immunity defect` but were unreachable
  from the umbrella grouping. STAT2 Deficiency is a strong further candidate
  (type I interferon signalling) but does not yet carry an iuis_category
  assignment, so it is deliberately not listed — see the
  `iuis_category_backfill_candidates` discussion on the umbrella Inborn Errors
  of Immunity grouping, which tracks this across all tables.