Fibrotic Disorders (Conserved Fibrotic Response)

name: Fibrotic Disorders
display_name: Fibrotic Disorders (Conserved Fibrotic Response)
creation_date: "2026-06-13T00:00:00Z"
description: >-
  A mechanistically defined group of disorders that converge on the conserved
  fibrotic response: tissue injury and inflammation drive activation of
  mesenchymal cells into ECM-secreting myofibroblasts, whose excessive and
  poorly resolved extracellular-matrix deposition distorts tissue architecture
  and impairs organ function. The group deliberately spans organs and etiologies
  — pulmonary, hepatic, and soft-tissue fibrosis of genetic, autoimmune,
  vascular, and idiopathic origin — to capture fibrosis as a shared final common
  pathway rather than an organ-specific diagnosis.
grouping_basis:
- SHARED_MECHANISM
grouping_rationale: >-
  Grouped on a shared convergent mechanism: each member conforms to the
  fibrotic_response module (tissue injury -> inflammatory amplification ->
  mesenchymal/myofibroblast activation -> excessive ECM deposition ->
  architectural distortion). Members are kept as separate Disease entries because
  the initiating insult differs enormously (genetic surfactant/telomere biology
  in IPF, copper toxicity in Wilson disease, hepatic outflow obstruction in
  Budd-Chiari, granulomatous inflammation in sarcoidosis, IgG4 plasmacytic
  inflammation, traumatic muscle loss). The criteria are NECESSARY: fibrotic-
  response conformance is entailed by membership, but fibrosis accompanies a
  vast number of diseases, so the mechanism alone is explicitly not sufficient
  to define this curated set.
membership_criteria:
- description: >-
    A member conforms to the conserved fibrotic-response module — injury/
    inflammation driving myofibroblast activation and excessive ECM deposition
    with architectural distortion of the affected organ.
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: fibrotic_response#Mesenchymal Cell Activation
    description: >-
      Conforms to the mesenchymal/myofibroblast activation node of the fibrotic
      response module.
members:
- member: Idiopathic Pulmonary Fibrosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Repetitive alveolar epithelial injury (with MUC5B and telomere-biology risk
      alleles) drives fibroblast-foci myofibroblast activation and progressive
      pulmonary fibrosis — the archetypal organ-restricted progressive fibrosis.
    gene:
      preferred_term: MUC5B
      term:
        id: hgnc:7516
        label: MUC5B
- member: Wilson Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      ATP7B-mediated copper accumulation injures hepatocytes, driving hepatic
      stellate-cell activation and cirrhosis — fibrosis secondary to a defined
      metabolic toxicity.
    gene:
      preferred_term: ATP7B
      term:
        id: hgnc:870
        label: ATP7B
- member: Budd-Chiari Syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Hepatic venous outflow obstruction (often JAK2-driven myeloproliferative
      thrombosis) causes congestive injury and centrilobular fibrosis — a
      vascular/congestive route into the fibrotic response.
    gene:
      preferred_term: JAK2
      term:
        id: hgnc:6192
        label: JAK2
- member: Hepatic Fibrinogen Storage Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Aggregation-prone FGG fibrinogen variants are retained in hepatocyte ER,
      causing chronic injury and hepatic fibrosis — a protein-storage route into
      the fibrotic pathway.
    gene:
      preferred_term: FGG
      term:
        id: hgnc:3694
        label: FGG
- member: Hepatic veno-occlusive disease-immunodeficiency syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      SP110 deficiency combines immunodeficiency with hepatic sinusoidal
      obstruction, producing veno-occlusive fibrosis of the liver.
    gene:
      preferred_term: SP110
      term:
        id: hgnc:5401
        label: SP110
- member: Sarcoidosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Granulomatous inflammation (HLA-DRB1-associated) can progress to pulmonary
      and multi-organ fibrosis — an immune-granulomatous initiator of the
      fibrotic response.
    gene:
      preferred_term: HLA-DRB1
      term:
        id: hgnc:4948
        label: HLA-DRB1
- member: IgG4-Related Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      A systemic immune-mediated condition in which IgG4-plasmacytic
      inflammation drives characteristic storiform fibrosis across organs — an
      autoimmune/plasmacytic initiator of the fibrotic response.
- member: Dupuytren Contracture
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Localized palmar fascial myofibroblast proliferation (with WNT-pathway
      SFRP4 dysregulation) produces a nodular contractile fibrosis — a focal
      soft-tissue fibromatosis.
    gene:
      preferred_term: SFRP4
      term:
        id: hgnc:10778
        label: SFRP4
- member: Volumetric Muscle Loss
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Traumatic loss of muscle exceeding regenerative capacity is repaired by
      fibrotic scar rather than functional myofibers — a post-traumatic,
      regeneration-failure route into the fibrotic response.
notes: >-
  An intentionally cross-organ SHARED_MECHANISM grouping that illustrates
  fibrosis as a final common pathway. The differentiating axis is the initiating
  insult (epithelial injury, metabolic toxicity, vascular congestion, protein
  storage, granulomatous/plasmacytic inflammation, trauma) feeding a common
  myofibroblast-ECM endpoint.
  MONDO mapping: deliberately omitted. Fibrosis is a phenotype/process (it has HP
  terms but no cross-organ MONDO disease-grouping class); the members are
  scattered across organ-system and etiologic MONDO branches. This grouping is a
  pure SHARED_MECHANISM convergence union, so no single MONDO class corresponds
  and the descendant-prioritization tool does not apply.