id: Q9H6U8
gene_symbol: ALG9
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ALG9 is a Dol-P-Man-dependent alpha-1,2-mannosyltransferase of the glycosyltransferase 22
  (GT22) family that acts in the assembly of the dolichol-linked oligosaccharide (LLO), the
  14-sugar glycan precursor used for protein N-linked glycosylation. It is a multi-pass
  endoplasmic reticulum membrane protein whose catalytic mannose-transfer steps occur on the
  lumenal side of the ER membrane. Using dolichyl-phosphate-mannose (Dol-P-Man, not GDP-mannose)
  as the mannose donor, ALG9 catalyses two sequential lumenal reactions in LLO assembly. It adds
  the seventh alpha-1,2-linked mannose onto Man(6)GlcNAc(2)-PP-dolichol (EC 2.4.1.259) and the
  ninth alpha-1,2-linked mannose onto Man(8)GlcNAc(2)-PP-dolichol (EC 2.4.1.261). Loss of ALG9
  function causes intracellular accumulation of GlcNAc(2)Man(6) and GlcNAc(2)Man(8) lipid-linked
  intermediates and hypoglycosylation of serum glycoproteins. Biallelic pathogenic variants cause
  ALG9-CDG (congenital disorder of glycosylation type Il, CDG-Il) and the severe skeletal
  dysplasia Gillessen-Kaesbach-Nishimura syndrome.
alternative_products:
- name: '1'
  id: Q9H6U8-1
- name: '2'
  id: Q9H6U8-2
  sequence_note: VSP_015434
- name: '3'
  id: Q9H6U8-3
  sequence_note: VSP_015435
- name: '4'
  id: Q9H6U8-4
  sequence_note: VSP_015434, VSP_015435
existing_annotations:
- term:
    id: GO:0000026
    label: alpha-1,2-mannosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assignment of the parent alpha-1,2-mannosyltransferase molecular
      function. This is correct but general; ALG9's two experimentally defined activities are the
      more specific Dol-P-Man Man(6/8)GlcNAc(2)-PP-Dol terms (GO:0052926, GO:0052918).
    action: MARK_AS_OVER_ANNOTATED
    reason: The activity is correct for ALG9 but is the generic parent of the two EC-specific
      terms it actually catalyses. The specific terms capture the exact substrate and donor and
      are the core molecular functions; this broad term is retained as accurate-but-general.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: the addition of the seventh and ninth alpha-1,2-linked
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: ALG9 is a multi-pass ER membrane protein and is active in the ER membrane, consistent
      with the phylogenetic assignment and with UniProt subcellular location.
    action: ACCEPT
    reason: ER membrane localization is well supported. UniProt records the subcellular location
      as ER membrane, multi-pass membrane protein, and the topology assigns seven transmembrane
      helices; the IBA assignment is at the correct level.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Multi-pass membrane protein
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ALG9 builds the LLO glycan precursor that is transferred en bloc to nascent proteins,
      so it is involved in protein N-linked glycosylation. Correct but broader than the LLO
      biosynthetic-process term.
    action: ACCEPT
    reason: The LLO that ALG9 helps assemble is the substrate for protein N-glycosylation, and
      ALG9 deficiency causes hypoglycosylation of serum glycoproteins (CDG). The IBA assignment
      is appropriate at this level.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: the glycan precursors employed in
    - reference_id: PMID:15945070
      supporting_text: Hypoglycosylation was confirmed by the typical CDG type 1 pattern
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt SubCell mapping of the ER membrane subcellular location. Consistent with all
      other evidence for ER membrane localization.
    action: ACCEPT
    reason: Correct electronic mapping from the UniProt subcellular-location annotation; agrees
      with the IBA and Reactome ER membrane annotations.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
- term:
    id: GO:0016757
    label: glycosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO mapping to the generic glycosyltransferase activity from the GT22 and
      Glyco_transf_22 domain (IPR005599). Correct but very general.
    action: MARK_AS_OVER_ANNOTATED
    reason: The domain-based mapping is accurate (ALG9 is a glycosyltransferase) but is a broad
      grandparent of the specific mannosyltransferase activities ALG9 actually catalyses. Kept as
      accurate-but-general rather than removed.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Belongs to the glycosyltransferase 22 family.
- term:
    id: GO:0052918
    label: dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic (RHEA/EC) assignment of the activity that adds the ninth mannose onto
      Man(8)GlcNAc(2)-PP-dolichol (EC 2.4.1.261, RHEA 29539). This is one of the two core
      catalytic activities of ALG9 and is independently supported experimentally.
    action: ACCEPT
    reason: EC 2.4.1.261 is one of ALG9's two experimentally established catalytic activities
      (UniProt CATALYTIC ACTIVITY, ECO 0000269 PubMed 15148656 and PubMed 15945070); the
      RHEA/EC electronic mapping correctly assigns this specific term.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: EC=2.4.1.261
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: the addition of the seventh and ninth alpha-1,2-linked
- term:
    id: GO:0052926
    label: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic (RHEA/EC) assignment of the activity that adds the seventh mannose onto
      Man(6)GlcNAc(2)-PP-dolichol (EC 2.4.1.259, RHEA 29531). This is the second core catalytic
      activity of ALG9 and is independently supported experimentally.
    action: ACCEPT
    reason: EC 2.4.1.259 is one of ALG9's two experimentally established catalytic activities
      (UniProt CATALYTIC ACTIVITY, ECO 0000269 PubMed 15148656 and PubMed 15945070); the
      RHEA/EC electronic mapping correctly assigns this specific term.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: EC=2.4.1.259
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: the addition of the seventh and ninth alpha-1,2-linked
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446193
  qualifier: involved_in
  review:
    summary: Reactome traceable assignment placing ALG9 in the biosynthesis of the dolichol
      lipid-linked oligosaccharide (LLO) N-glycan precursor. This is the most precise core
      biological process for ALG9.
    action: ACCEPT
    reason: ALG9 performs two of the mannose-addition steps in LLO assembly; the Reactome pathway
      covers the 14-step synthesis of the dolichol lipid-linked oligosaccharide precursor.
    supported_by:
    - reference_id: Reactome:R-HSA-446193
      supporting_text: N-linked glycosylation commences with the 14-step synthesis of a dolichol
        lipid-linked oligosaccharide (LLO)
- term:
    id: GO:0098553
    label: lumenal side of endoplasmic reticulum membrane
  evidence_type: IC
  original_reference_id: PMID:15148656
  qualifier: is_active_in
  review:
    summary: Curator inference (IC) that ALG9 is active on the lumenal side of the ER membrane.
      The Dol-P-Man-dependent mannose additions catalysed by ALG9 occur in the ER lumen, so this
      refinement of the ER membrane location is well justified.
    action: ACCEPT
    reason: LLO assembly finishes in the ER lumen, and ALG9's mannose-transfer reactions are
      lumenal (UniProt FUNCTION; Reactome). This IC annotation appropriately specifies the
      lumenal side of the ER membrane as the site of catalysis.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: begins on the cytosolic side of the endoplasmic
    - reference_id: Reactome:R-HSA-446215
      supporting_text: This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose
        as the mannose donor
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IMP
  original_reference_id: PMID:15148656
  qualifier: involved_in
  review:
    summary: Experimental (IMP) evidence that ALG9 is required for protein N-linked glycosylation.
      A CDG patient with an ALG9 deficiency (E523K) showed transfer of incomplete oligosaccharide
      precursors to protein, and the defect was confirmed by yeast complementation.
    action: ACCEPT
    reason: Frank et al. 2004 experimentally established the requirement of ALG9 for N-linked
      glycosylation via a patient defect plus yeast complementation. The full text was read by the
      curator; the abstract already documents the underglycosylation phenotype.
    supported_by:
    - reference_id: PMID:15148656
      supporting_text: paralleled by the transfer of incomplete oligosaccharides precursors to
        protein
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IMP
  original_reference_id: PMID:15945070
  qualifier: involved_in
  review:
    summary: Second experimental (IMP) confirmation, in an independent CDG-Il patient (p.Y286C),
      that ALG9 deficiency impairs protein N-linked glycosylation, shown by the typical CDG type 1
      transferrin isoelectric-focusing pattern.
    action: ACCEPT
    reason: Weinstein et al. 2005 report a second ALG9-deficient patient with confirmed
      hypoglycosylation and yeast-complementation validation of the causal mutation, supporting
      the requirement of ALG9 for N-glycosylation.
    supported_by:
    - reference_id: PMID:15945070
      supporting_text: Hypoglycosylation was confirmed by the typical CDG type 1 pattern
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IGI
  original_reference_id: PMID:15148656
  qualifier: involved_in
  review:
    summary: Genetic-interaction (IGI) evidence with S. cerevisiae ALG9 (UniProtKB P53868).
      Functional homology and rescue of the alg9-deficient yeast confirmed ALG9's role in LLO
      biosynthesis, with patient cells accumulating GlcNAc(2)Man(6) and GlcNAc(2)Man(8) LLO.
    action: ACCEPT
    reason: The yeast complementation assay and the accumulation of the two LLO intermediates
      directly place ALG9 in the dolichol-linked oligosaccharide biosynthetic process; this is a
      core biological process for the gene.
    supported_by:
    - reference_id: PMID:15148656
      supporting_text: accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures
    - reference_id: PMID:15148656
      supporting_text: confirmed by a yeast
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IGI
  original_reference_id: PMID:15945070
  qualifier: involved_in
  review:
    summary: Second genetic-interaction (IGI) with yeast ALG9 (UniProtKB P53868). The causal
      effect of the patient mutation was demonstrated by complementation in alg9-deficient yeast,
      with accumulation of DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8 confirming the LLO defect.
    action: ACCEPT
    reason: Independent yeast-complementation evidence for ALG9's role in LLO biosynthesis,
      corroborating the core biological process assignment.
    supported_by:
    - reference_id: PMID:15945070
      supporting_text: shown by complementation assays in alg9 deficient
    - reference_id: PMID:15945070
      supporting_text: accumulation of the DolPP-GlcNAc2Man6 and
- term:
    id: GO:0052918
    label: dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  evidence_type: IGI
  original_reference_id: PMID:15148656
  qualifier: enables
  review:
    summary: Genetic-interaction (IGI) evidence, via yeast ALG9 complementation, for the activity
      that adds the ninth mannose (EC 2.4.1.261). Accumulation of GlcNAc(2)Man(8) LLO in patient
      cells directly indicates loss of the Man(8) to Man(9) mannosyltransferase step.
    action: ACCEPT
    reason: The Man(8)GlcNAc(2) accumulation, plus functional complementation of yeast alg9,
      supports ALG9's Man(8)-acceptor alpha-1,2-mannosyltransferase activity; a core molecular
      function. Experimental annotation, full text read by curator.
    supported_by:
    - reference_id: PMID:15148656
      supporting_text: accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures
- term:
    id: GO:0052918
    label: dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  evidence_type: IGI
  original_reference_id: PMID:15945070
  qualifier: enables
  review:
    summary: Second IGI (yeast complementation) supporting the Man(8)-acceptor alpha-1,2-
      mannosyltransferase activity (ninth-mannose addition, EC 2.4.1.261), with DolPP-GlcNAc2Man8
      accumulating in the patient's fibroblasts.
    action: ACCEPT
    reason: Independent genetic evidence for the Man(8)GlcNAc(2)-PP-Dol mannosyltransferase
      activity; corroborates the core molecular function.
    supported_by:
    - reference_id: PMID:15945070
      supporting_text: accumulation of the DolPP-GlcNAc2Man6 and
- term:
    id: GO:0052926
    label: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  evidence_type: IGI
  original_reference_id: PMID:15148656
  qualifier: enables
  review:
    summary: Genetic-interaction (IGI) evidence, via yeast ALG9 complementation, for the activity
      that adds the seventh mannose (EC 2.4.1.259). Accumulation of GlcNAc(2)Man(6) LLO in patient
      cells directly indicates loss of the Man(6) to Man(7) mannosyltransferase step.
    action: ACCEPT
    reason: The Man(6)GlcNAc(2) accumulation, plus functional complementation of yeast alg9,
      supports ALG9's Man(6)-acceptor alpha-1,2-mannosyltransferase activity; a core molecular
      function. Experimental annotation, full text read by curator.
    supported_by:
    - reference_id: PMID:15148656
      supporting_text: accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures
- term:
    id: GO:0052926
    label: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  evidence_type: IGI
  original_reference_id: PMID:15945070
  qualifier: enables
  review:
    summary: Second IGI (yeast complementation) supporting the Man(6)-acceptor alpha-1,2-
      mannosyltransferase activity (seventh-mannose addition, EC 2.4.1.259), with DolPP-GlcNAc2Man6
      accumulating in the patient's fibroblasts.
    action: ACCEPT
    reason: Independent genetic evidence for the Man(6)GlcNAc(2)-PP-Dol mannosyltransferase
      activity; corroborates the core molecular function.
    supported_by:
    - reference_id: PMID:15945070
      supporting_text: accumulation of the DolPP-GlcNAc2Man6 and
- term:
    id: GO:0000026
    label: alpha-1,2-mannosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446215
  qualifier: enables
  review:
    summary: Reactome TAS for the alpha-1,2-mannosyltransferase activity, specifically the reaction
      in which ALG9 adds the seventh mannose to the (GlcNAc)2(Man)6(PP-Dol)1 precursor in the ER
      lumen. Correct but at the generic parent level.
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct activity, but the generic parent of the EC-specific GO:0052926 term that
      precisely captures this Man(6)-acceptor reaction; retained as accurate-but-general.
    supported_by:
    - reference_id: Reactome:R-HSA-446215
      supporting_text: The seventh mannose is added to the N-glycan precursor.
- term:
    id: GO:0000026
    label: alpha-1,2-mannosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446216
  qualifier: enables
  review:
    summary: Reactome TAS for the alpha-1,2-mannosyltransferase activity, specifically the reaction
      in which ALG9 adds the last (ninth) mannose to the (GlcNAc)2(Man)8(PP-Dol)1 precursor in the
      ER lumen. Correct but at the generic parent level.
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct activity, but the generic parent of the EC-specific GO:0052918 term that
      precisely captures this Man(8)-acceptor reaction; retained as accurate-but-general.
    supported_by:
    - reference_id: Reactome:R-HSA-446216
      supporting_text: The last mannose is added to the N-glycan precursor.
- term:
    id: GO:0000026
    label: alpha-1,2-mannosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4720478
  qualifier: enables
  review:
    summary: Reactome TAS derived from the disease reaction "Defective ALG9 does not add the
      seventh mannose", asserting the normal alpha-1,2-mannosyltransferase activity of ALG9.
      Correct but generic.
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct activity but the generic parent of the specific EC-mapped terms; retained as
      accurate-but-general.
    supported_by:
    - reference_id: Reactome:R-HSA-4720478
      supporting_text: It adds the 7th and 9th mannose moieties to LLO.
- term:
    id: GO:0000026
    label: alpha-1,2-mannosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9035514
  qualifier: enables
  review:
    summary: Reactome TAS derived from the disease reaction "Defective ALG9 does not add the last
      mannose", asserting the normal alpha-1,2-mannosyltransferase activity of ALG9. Correct but
      generic.
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct activity but the generic parent of the specific EC-mapped terms; retained as
      accurate-but-general.
    supported_by:
    - reference_id: Reactome:R-HSA-9035514
      supporting_text: It adds the 7th and 9th mannose moieties to LLO.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4720478
  qualifier: located_in
  review:
    summary: Reactome TAS localizing ALG9 to the ER membrane, from the CDG disease reaction. Agrees
      with all other ER membrane evidence.
    action: ACCEPT
    reason: Consistent ER membrane localization; ALG9's lumenal mannose additions occur at the ER
      membrane.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9035514
  qualifier: located_in
  review:
    summary: Reactome TAS localizing ALG9 to the ER membrane, from the CDG disease reaction. Agrees
      with all other ER membrane evidence.
    action: ACCEPT
    reason: Consistent ER membrane localization for this multi-pass membrane enzyme.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput proteomics (HDA) detected ALG9 in an NK-cell membrane-proteome study.
      Consistent with ALG9 being an integral membrane protein but far less specific than the
      ER membrane annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: ALG9 is a multi-pass membrane protein, so detection in a membrane proteome is
      expected, but the generic membrane term is uninformative relative to the well-supported
      ER membrane localization. Kept as accurate-but-general.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: Isolated membranes were
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Multi-pass membrane protein
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446215
  qualifier: located_in
  review:
    summary: Reactome TAS localizing ALG9 to the ER membrane, from the seventh-mannose transfer
      reaction. Agrees with all other ER membrane evidence.
    action: ACCEPT
    reason: Consistent ER membrane localization.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446216
  qualifier: located_in
  review:
    summary: Reactome TAS localizing ALG9 to the ER membrane, from the last-mannose transfer
      reaction. Agrees with all other ER membrane evidence.
    action: ACCEPT
    reason: Consistent ER membrane localization.
    supported_by:
    - reference_id: file:human/ALG9/ALG9-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
core_functions:
- description: Dol-P-Man-dependent alpha-1,2-mannosyltransferase adding the seventh mannose onto
    Man(6)GlcNAc(2)-PP-dolichol during lumenal LLO assembly (EC 2.4.1.259)
  molecular_function:
    id: GO:0052926
    label: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  directly_involved_in:
  - id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  - id: GO:0006487
    label: protein N-linked glycosylation
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/ALG9/ALG9-uniprot.txt
    supporting_text: the addition of the seventh and ninth alpha-1,2-linked
  - reference_id: PMID:15148656
    supporting_text: accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures
- description: Dol-P-Man-dependent alpha-1,2-mannosyltransferase adding the ninth (last) mannose
    onto Man(8)GlcNAc(2)-PP-dolichol during lumenal LLO assembly (EC 2.4.1.261)
  molecular_function:
    id: GO:0052918
    label: dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
  directly_involved_in:
  - id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  - id: GO:0006487
    label: protein N-linked glycosylation
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/ALG9/ALG9-uniprot.txt
    supporting_text: the addition of the seventh and ninth alpha-1,2-linked
  - reference_id: PMID:15148656
    supporting_text: accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15148656
  title: 'Identification and functional analysis of a defect in the human ALG9 gene:
    definition of congenital disorder of glycosylation type IL.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache. Establishes ALG9 as the alpha-1,2-mannosyltransferase
      whose deficiency (E523K) accumulates GlcNAc2Man6/GlcNAc2Man8 LLO and defines CDG-IL;
      confirmed by yeast complementation. Supports the MF, LLO-biosynthesis BP, and
      N-glycosylation IMP annotations.
- id: PMID:15945070
  title: 'CDG-IL: an infant with a novel mutation in the ALG9 gene and additional
    phenotypic features.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache. Second CDG-IL patient (p.Y286C); DolPP-GlcNAc2Man6/Man8
      accumulation and yeast complementation independently corroborate ALG9's LLO
      mannosyltransferase function and role in N-glycosylation.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput NK-cell membrane proteomics; supports only the generic
      membrane localization, not a specific ALG9 function.
- id: Reactome:R-HSA-446193
  title: Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide,
    LLO) and transfer to a nascent protein
  findings: []
- id: Reactome:R-HSA-446215
  title: ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)6 (PP-Dol)1
  findings: []
- id: Reactome:R-HSA-446216
  title: ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)8 (PP-Dol)1
  findings: []
- id: Reactome:R-HSA-4720478
  title: Defective ALG9 does not add the seventh mannose to the N-glycan precursor
  findings: []
- id: Reactome:R-HSA-9035514
  title: Defective ALG9 does not add the last mannose to the N-glycan precursor
  findings: []
- id: file:human/ALG9/ALG9-uniprot.txt
  title: UniProtKB entry Q9H6U8 (ALG9_HUMAN), Alpha-1,2-mannosyltransferase ALG9
  findings: []