Other Disorders of Multiple Glycosylation Pathways

name: Other Disorders of Multiple Glycosylation Pathways
display_name: Other Disorders of Multiple Glycosylation Pathways
creation_date: "2026-07-06T06:04:18Z"
description: >-
  This grouping collects rare inherited glycosylation disorders in which the
  primary lesion is not a single canonical N-glycan assembly enzyme or Golgi
  processing enzyme, but instead affects nucleotide-sugar precursor supply or
  ER glycoprotein quality control with consequences across multiple glycan or
  glycoprotein pathways. The work-package members are UGDH-related DEE84,
  UGP2-related DEE83, and UGGT1-CDG.
grouping_basis:
- SHARED_PATHWAY
grouping_rationale: >-
  These entries are kept as separate Disease entries because their proximal
  lesions are distinct: UGDH limits UDP-glucuronic acid supply for
  glycosaminoglycan/proteoglycan and glycolipid production; UGP2 limits
  UDP-glucose-dependent glycogen and protein glycosylation biology in brain;
  and UGGT1 disrupts ER reglucosylation-based quality control of N-linked
  glycoproteins. They are grouped only at the pathway-placement level as
  "other/multiple glycosylation pathway" disorders rather than merged into a
  single disease entity.
membership_criteria:
- description: >-
    A member has a primary lesion in a nucleotide-sugar precursor pathway,
    glycosaminoglycan/proteoglycan biosynthesis, or ER N-glycoprotein quality
    control that affects more than one downstream glycan or glycoprotein client
    class.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    description: >-
      Multiple-pathway glycosylation defects represented by glycoprotein
      biosynthesis generally, glycosaminoglycan biosynthesis, a named
      N- or O-linked branch, or ER folding quality control. The branch-generic
      operand is first because it is the level this grouping actually means: a
      member is here precisely because its lesion is not specific to one branch,
      so requiring a named branch contradicted the grouping's own concept and
      left UGP2-CDG, whose entry correctly declines to name one, NOT_SATISFIED.
    operands:
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: >-
        Impairs glycoprotein biosynthesis without the lesion being specific to a
        named glycosylation branch. Ontology closure makes this subsume the
        N- and O-linked operands below, which are kept because they say which
        branch a member that does name one perturbs.
      biological_processes:
      - preferred_term: protein glycosylation
        term:
          id: GO:0009101
          label: glycoprotein biosynthetic process
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Impairs glycosaminoglycan biosynthesis.
      biological_processes:
      - preferred_term: glycosaminoglycan biosynthetic process
        term:
          id: GO:0006024
          label: glycosaminoglycan biosynthetic process
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Impairs protein O-linked glycosylation.
      biological_processes:
      - preferred_term: protein O-linked glycosylation
        term:
          id: GO:0006493
          label: protein O-linked glycosylation
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Perturbs protein N-linked glycosylation.
      biological_processes:
      - preferred_term: protein N-linked glycosylation
        term:
          id: GO:0006487
          label: protein N-linked glycosylation
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Perturbs ER protein-folding quality control.
      biological_processes:
      - preferred_term: protein folding in endoplasmic reticulum
        term:
          id: GO:0034975
          label: protein folding in endoplasmic reticulum
members:
- member: UGDH-related developmental and epileptic encephalopathy 84
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      UGDH loss reduces conversion of UDP-glucose to UDP-glucuronic acid,
      limiting precursor supply for glycosaminoglycan-rich proteoglycans and
      glycolipids.
    gene:
      preferred_term: UGDH
      term:
        id: hgnc:12525
        label: UGDH
    biological_processes:
    - preferred_term: glycosaminoglycan biosynthetic process
      modifier: DECREASED
      term:
        id: GO:0006024
        label: glycosaminoglycan biosynthetic process
- member: UGP2-related developmental and epileptic encephalopathy 83
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      UGP2 short-isoform loss in brain reduces UDP-glucose production in neural
      stem cells, affecting glycogen metabolism, glycosylation, and ER
      proteostasis.
    gene:
      preferred_term: UGP2
      term:
        id: hgnc:12527
        label: UGP2
    biological_processes:
    - preferred_term: protein N-linked glycosylation
      modifier: ABNORMAL
      term:
        id: GO:0006487
        label: protein N-linked glycosylation
- member: Autosomal Recessive Cutis Laxa Type 2A
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      ATP6V0A2, the Golgi V-ATPase a2 subunit. The lesion is Golgi luminal
      acidification, not a transferase or a nucleotide-sugar pool, and it
      disables N- and O-linked glycosylation together — which is what places it
      here rather than in a branch-specific sibling. The distinguishing
      consequence is defective elastic-fibre assembly, giving cutis laxa beside
      the neuronal migration defect.
    gene:
      preferred_term: ATP6V0A2
      term:
        id: hgnc:18481
        label: ATP6V0A2
- member: Short Stature, Amelogenesis Imperfecta, and Skeletal Dysplasia with Scoliosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      SLC10A7, a Golgi calcium-handling transporter. Like the ATP6V0A2 member the
      proximal lesion is a Golgi luminal condition rather than a glycosylation
      enzyme, but the perturbed variable is calcium rather than pH, and the
      client range extends to glycosaminoglycan synthesis as well as N- and
      O-glycans — hence a skeletal dysplasia with amelogenesis imperfecta.
    gene:
      preferred_term: SLC10A7
      term:
        id: hgnc:23088
        label: SLC10A7
- member: UGGT1-congenital disorder of glycosylation
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      UGGT1 variants impair reglucosylation and ER retention of the
      UDP-glucose:glycoprotein glucosyltransferase quality-control enzyme for
      N-linked glycoproteins.
    gene:
      preferred_term: UGGT1
      term:
        id: hgnc:15663
        label: UGGT1
    biological_processes:
    - preferred_term: protein folding in endoplasmic reticulum
      modifier: ABNORMAL
      term:
        id: GO:0034975
        label: protein folding in endoplasmic reticulum
notes: >-
  This is an auditable work-package subgroup, not an attempt to replace the
  broader Congenital Disorders of Glycosylation grouping or the MONDO hierarchy.