BBSome-opathies (BBSome Machine Disorders)

name: BBSome-opathies
display_name: BBSome-opathies (BBSome Machine Disorders)
creation_date: "2026-06-14T00:00:00Z"
description: >-
  The BBSome-opathies are the subset of ciliopathies caused by lesions in the
  BBSome molecular machine itself - its eight obligate core subunits (BBS1, BBS2,
  BBS4, BBS5, BBS7, TTC8/BBS8, BBS9, BBIP1/BBS18), its chaperonin-like assembly
  factors (MKKS/BBS6, BBS10, BBS12), and its dedicated operators ARL6/BBS3 (the
  membrane-recruiting GTPase), LZTFL1/BBS17, and the BBSome-recycling GTPase
  IFT27 - as distinct from the broader set of transition-zone, basal-body, and
  general intraflagellar-transport genes that also produce ciliopathy
  phenotypes. The members share the BBSome trafficking mechanism and differ
  chiefly in WHICH cilia-dependent organ branches cross the clinical threshold:
  Bardet-Biedl syndrome lights up all branches; McKusick-Kaufman syndrome the
  limb (Hedgehog) and genitourinary branches; and BBSome-related retinitis
  pigmentosa only the photoreceptor branch.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PATHWAY
grouping_rationale: >-
  Grouped on the defining BBSome-machine mechanism: every member conforms to the
  bbsome_trafficking module (BBSome subunit/assembly or membrane-recruitment
  defect -> BBSome-dependent ciliary cargo trafficking failure). This is a
  deliberately STRICTER union than the parent Ciliopathies grouping: it is scoped
  to the BBSome machine plus its dedicated operators and excludes transition-zone
  (CEP290, MKS1, SDCCAG8, NPHP1), general IFT-B (IFT74, IFT172), and basal-body
  genes that also cause the Bardet-Biedl phenotype but are not part of the
  BBSome machine - those are modeled in the ciliopathy_dysfunction module.
  Members are kept as separate Disease entries because they are distinct clinical
  and MONDO entities differing in organ-branch involvement and management. The
  criterion is stated as NECESSARY_AND_SUFFICIENT because conformance to the
  BBSome trafficking module both is entailed by membership (used to audit
  members) and defines the class (used to discover candidate members among
  disorders that conform to the module).
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0005308
      label: ciliopathy
    mapping_predicate: skos:broadMatch
    mapping_source: MONDO
    mapping_justification: >-
      The BBSome-opathies are a strict molecular subset of the MONDO ciliopathy
      class; broadMatch because MONDO has no dedicated "BBSome machine disorder"
      node and the parent ciliopathy class is broader than this BBSome-scoped
      union.
membership_criteria:
- description: >-
    A disorder is a BBSome-opathy if and only if it conforms to the BBSome
    trafficking module - i.e., a defect in the BBSome machine (subunits,
    chaperonin assembly factors, or dedicated operators) causing BBSome-dependent
    ciliary cargo trafficking failure.
  criteria_semantics: NECESSARY_AND_SUFFICIENT
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: bbsome_trafficking#BBSome-Dependent Ciliary Cargo Trafficking Failure
    description: >-
      Conforms to the BBSome trafficking module at the shared cargo-trafficking
      failure node.
members:
- member: Bardet-Biedl syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The full syndrome: BBSome-machine loss (subunit, chaperonin, or operator
      genes; typically null alleles) crosses the clinical threshold in all
      cilia-dependent organ branches - retinal, hypothalamic/metabolic
      (obesity), limb (polydactyly), renal, and cognitive.
    module: bbsome_trafficking
- member: McKusick-Kaufman syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      MKKS/BBS6 chaperonin defect expressed in the limb (Hedgehog) and
      genitourinary developmental branches - postaxial polydactyly,
      hydrometrocolpos, and congenital heart disease - classically without the
      retinal dystrophy and obesity of Bardet-Biedl syndrome. Allelic to
      Bardet-Biedl syndrome 6.
    gene:
      preferred_term: MKKS
      term:
        id: hgnc:7108
        label: MKKS
    module: bbsome_trafficking
- member: BBSome-related retinitis pigmentosa
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The photoreceptor-restricted floor of the spectrum: hypomorphic or
      tissue-restricted BBSome-machine alleles (e.g. the BBS8 retina-specific
      exon, the BBS3L isoform, the mild BBS1 p.M390R allele) cause partial
      BBSome trafficking loss expressed only in the photoreceptor, producing
      non-syndromic retinitis pigmentosa.
    module: bbsome_trafficking
    modifier: DECREASED