Congenital Disorders of Deglycosylation (CDDG)

name: Congenital Disorders of Deglycosylation
display_name: Congenital Disorders of Deglycosylation (CDDG)
creation_date: "2026-07-06T06:04:18Z"
description: >-
  Congenital disorders of deglycosylation are inherited disorders of glycan
  removal and free-glycan catabolism. The local curated members are
  NGLY1-CDDG, caused by failure to deglycosylate misfolded N-linked
  glycoproteins during ER-associated degradation, and MAN2C1-CDDG2, caused by
  impaired cytosolic catabolism of free oligosaccharides generated during
  N-glycosylation and glycoprotein turnover.
grouping_basis:
- SHARED_PATHWAY
grouping_rationale: >-
  NGLY1-CDDG and MAN2C1-CDDG2 are kept as separate Disease entries because they
  act at distinct deglycosylation/catabolic steps and have different clinical
  spectra. They are grouped because both disrupt the downstream removal or
  processing of glycans rather than the initial assembly of glycans on protein.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0031376
      label: congenital disorder of deglycosylation
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: >-
      The grouping concept corresponds to MONDO congenital disorder of
      deglycosylation. Additional MONDO descendants without DisMech entries
      would be curation gaps rather than a reason to change this mapping.
membership_criteria:
- description: >-
    A member is caused by a defect in deglycosylation of N-linked
    glycoproteins, or in the downstream cytosolic catabolism of free
    oligosaccharides generated from glycoprotein turnover.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    description: Deglycosylation or free-oligosaccharide catabolism defect.
    operands:
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Impairs protein deglycosylation.
      biological_processes:
      - preferred_term: protein deglycosylation
        term:
          id: GO:0006517
          label: protein deglycosylation
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Impairs free-oligosaccharide catabolism.
      biological_processes:
      - preferred_term: oligosaccharide catabolic process
        term:
          id: GO:0009313
          label: oligosaccharide catabolic process
members:
- member: NGLY1-congenital disorder of deglycosylation
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      NGLY1 encodes cytosolic N-glycanase 1; deficiency blocks removal of
      N-glycans from misfolded glycoproteins retrotranslocated for ERAD and
      proteasomal degradation.
    gene:
      preferred_term: NGLY1
      term:
        id: hgnc:17646
        label: NGLY1
    biological_processes:
    - preferred_term: protein deglycosylation
      modifier: DECREASED
      term:
        id: GO:0006517
        label: protein deglycosylation
- member: MAN2C1-congenital disorder of deglycosylation 2
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      MAN2C1 encodes a cytosolic alpha-mannosidase; deficiency delays trimming
      and catabolism of free oligosaccharides, causing their accumulation in
      patient-derived cells.
    gene:
      preferred_term: MAN2C1
      term:
        id: hgnc:6827
        label: MAN2C1
    biological_processes:
    - preferred_term: oligosaccharide catabolic process
      modifier: DECREASED
      term:
        id: GO:0009313
        label: oligosaccharide catabolic process
notes: >-
  The grouping boundary follows the deglycosylation mechanism rather than the
  broad clinical overlap with congenital disorders of glycosylation.

  Membership completeness (checked 2026-08-20 against the MONDO 2026-08
  release): MONDO:0031376 has exactly two is-a descendants —
  MONDO:0800044 (CDDG1, NGLY1) and MONDO:0030770 (CDDG2, MAN2C1) — and both are
  curated here, so this grouping is MONDO-complete. MONDO:0031376 xrefs the
  OMIM phenotypic series OMIMPS:615273, which was not independently
  enumerated here. Completeness
  is therefore a statement about the small size of the concept, not about the
  depth of the member entries, which remain the thinnest pair in the
  glycosylation groupings.

  Mechanistic thread worth preserving if a third member appears: both members
  are cytosolic, post-ER steps acting on glycans that have already been made
  — NGLY1 releases the N-glycan from an ERAD substrate, MAN2C1 trims the free
  oligosaccharide that release (and glycoprotein turnover) generates. The two
  sit in sequence on the same free-oligosaccharide pool, which is why the
  NECESSARY criteria are an OR over deglycosylation and free-oligosaccharide
  catabolism rather than a single process.