id: Q7Z7B1
gene_symbol: PIGW
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PIGW (phosphatidylinositol-glycan biosynthesis class W protein; PIG-W) is the GPI inositol
  acyltransferase of glycosylphosphatidylinositol (GPI) anchor biosynthesis. It is a multi-pass
  endoplasmic reticulum membrane protein that catalyses the fourth step of GPI-anchor assembly:
  transfer of an acyl group (usually palmitate) from acyl-CoA to the 2-OH of the inositol ring of
  glucosaminyl-phosphatidylinositol (GlcN-PI), producing 2-acyl-GlcN-PI (GlcN-(acyl)PI). This
  inositol acyl group is required for downstream recognition of the GPI intermediate by the GPI
  transamidase complex and is normally removed by PGAP1 after the anchor is attached to protein.
  Through this activity PIGW is essential for the ER synthesis of GPI anchors and hence for the
  transport of GPI-anchored proteins to the cell surface. Biallelic loss-of-function variants cause
  an autosomal-recessive inherited GPI-deficiency disorder (glycosylphosphatidylinositol biosynthesis
  defect 11, GPIBD11) on the hyperphosphatasia-with-mental-retardation / epileptic-encephalopathy
  spectrum, characterised by developmental delay, intellectual disability, seizures (including West
  syndrome with hypsarrhythmia), dysmorphic features, and elevated serum alkaline phosphatase.
existing_annotations:
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      PIGW acts in the endoplasmic reticulum, where GPI-anchor biosynthesis occurs. This
      phylogenetic (IBA) location is correct but general; the ER membrane (GO:0005789) is the
      precise compartment for this multi-pass membrane enzyme.
    action: ACCEPT
    reason: >-
      Consistent with UniProt subcellular location and with GPI biosynthesis being an ER process.
      Kept as a correct-but-broad cellular component; the membrane-specific term is the core location.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Core biological process: PIGW catalyses the fourth step of GPI-anchor biosynthesis (inositol
      acylation of GlcN-PI). The IBA is well supported across orthologues (PomBase, SGD, CGD, RGD)
      and matches the human function.
    action: ACCEPT
    reason: >-
      This is the central biological role of PIGW and is corroborated experimentally and by UniProt.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "participates in the fourth step of GPI-anchor biosynthesis"
- term:
    id: GO:0032216
    label: glucosaminyl-phosphatidylinositol O-acyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Core molecular function: PIGW is the GPI inositol acyltransferase, transferring an acyl group
      from acyl-CoA to the 2-OH of the inositol of GlcN-PI. This specific term is the correct MF and
      is supported by the UniProt catalytic activity (RHEA:60496/RHEA:83759) and by the IBA across
      orthologues.
    action: ACCEPT
    reason: >-
      Specific, correct molecular function directly matching the characterised reaction.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Acyltransferase that catalyzes the acyl transfer from an"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      PIGW is a multi-pass ER membrane protein; the ER membrane is its precise location. This
      SubCell-mapping IEA is correct and represents the core cellular component.
    action: ACCEPT
    reason: >-
      Matches UniProt subcellular location (ER membrane, multi-pass) and the topology features.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Multi-pass membrane protein"
- term:
    id: GO:0006505
    label: GPI anchor metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      GPI anchor metabolic process is the broad parent of GPI anchor biosynthetic process. PIGW is a
      biosynthetic enzyme, so the more specific biosynthetic term (GO:0006506) is the informative
      core annotation. This ARBA-generated IEA to the parent is redundant with that specific term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Not wrong, but a less-informative parent that is fully subsumed by the accepted biosynthetic
      process annotation.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "participates in the fourth step of GPI-anchor biosynthesis"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Duplicate of the core GPI anchor biosynthetic process annotation, here via combined-IEA
      (InterPro IPR009447 / UniPathway UPA00196). Correct and consistent with the IBA/ISS/TAS
      annotations to the same term.
    action: ACCEPT
    reason: >-
      Correctly captures the core biosynthetic role; duplicates of a correct term are acceptable.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor"
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: >-
      Generic "membrane" from an InterPro2GO mapping. PIGW is specifically an ER membrane protein, so
      this uninformative parent is superseded by GO:0005789 (ER membrane).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Too general; the specific ER membrane location is annotated and preferred.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Generic acyltransferase activity from InterPro2GO. This is a broad parent of the specific,
      correct MF GO:0032216 (glucosaminyl-phosphatidylinositol O-acyltransferase activity).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Not wrong but uninformative relative to the specific inositol-acyltransferase term.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Acyltransferase that catalyzes the acyl transfer from an"
- term:
    id: GO:0032216
    label: glucosaminyl-phosphatidylinositol O-acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      Rhea-mapped IEA (RHEA:60496/RHEA:83759) to the specific GPI inositol acyltransferase activity,
      matching the UniProt catalytic activity. Duplicate of the accepted core MF term.
    action: ACCEPT
    reason: >-
      Correct specific molecular function derived from the curated Rhea reaction.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Acyltransferase that catalyzes the acyl transfer from an"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162710
  qualifier: involved_in
  review:
    summary: >-
      Reactome-traceable annotation to the core biosynthetic process, from the human GPI synthesis
      pathway (R-HSA-162710), in which PIGW catalyses the inositol-acylation step.
    action: ACCEPT
    reason: >-
      Correctly captures the core biosynthetic role, consistent with the IBA/IEA/ISS annotations.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "participates in the fourth step of GPI-anchor biosynthesis"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      ISS transfer of ER membrane localisation from the mouse orthologue (UniProtKB:Q7TSN4),
      consistent with the multi-pass ER membrane topology. Core cellular component.
    action: ACCEPT
    reason: >-
      Matches UniProt subcellular location for the human protein.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
- term:
    id: GO:0032216
    label: glucosaminyl-phosphatidylinositol O-acyltransferase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      ISS transfer of the GPI inositol acyltransferase activity from the mouse orthologue
      (UniProtKB:Q7TSN4). Duplicate of the accepted specific core MF term.
    action: ACCEPT
    reason: >-
      Correct specific molecular function, supported by orthology and the curated reaction.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Acyltransferase that catalyzes the acyl transfer from an"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS transfer of the core GPI-anchor biosynthetic process from the mouse orthologue
      (UniProtKB:Q7TSN4). Duplicate of the accepted core BP term.
    action: ACCEPT
    reason: >-
      Correct core biological process, supported by orthology.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "participates in the fourth step of GPI-anchor biosynthesis"
- term:
    id: GO:0016747
    label: acyltransferase activity, transferring groups other than amino-acyl groups
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162683
  qualifier: enables
  review:
    summary: >-
      Reactome-traceable annotation to a broad acyltransferase-class term for the inositol-acylation
      reaction (R-HSA-162683). This is a general parent of the specific MF GO:0032216.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Not wrong but uninformative relative to the specific glucosaminyl-PI O-acyltransferase term.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Acyltransferase that catalyzes the acyl transfer from an"
- term:
    id: GO:0006505
    label: GPI anchor metabolic process
  evidence_type: IC
  original_reference_id: PMID:24367057
  qualifier: involved_in
  review:
    summary: >-
      Curator-inferred (IC, from the GO:0072659 IMP in the same paper) annotation to the broad GPI
      anchor metabolic process. PIGW is specifically biosynthetic, so the biosynthetic child
      (GO:0006506) is the informative core term; this broad parent is a redundant over-annotation
      relative to the accepted biosynthetic-process term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Correct in essence (PIGW is in GPI-anchor metabolism) but a broad parent superseded by the
      specific biosynthetic-process term; kept rather than removed, consistent with the other
      GO:0006505 annotation.
    supported_by:
    - reference_id: PMID:24367057
      supporting_text: "involved in the addition of the acyl-chain to inositol in an early step of GPI"
- term:
    id: GO:0072659
    label: protein localization to plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:24367057
  qualifier: involved_in
  review:
    summary: >-
      Experimental (IMP) annotation from patient/variant studies: PIGW loss reduces surface
      expression of GPI-anchored proteins, i.e. PIGW is required for transport of GPI-APs to the
      plasma membrane. This is a downstream consequence of the enzyme's role in GPI-anchor synthesis
      rather than the direct molecular function, so it is retained as non-core.
    action: KEEP_AS_NON_CORE
    reason: >-
      Valid experimental phenotype (defer to curator; not removed). Represents a downstream cellular
      outcome of GPI-anchor biosynthesis, not PIGW's direct acyltransferase function.
    supported_by:
    - reference_id: PMID:24367057
      supporting_text: "decreased surface expression of GPI-APs on"
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "Required for the transport of GPI-anchored proteins to the"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162683
  qualifier: located_in
  review:
    summary: >-
      Reactome-traceable ER membrane localisation for the inositol-acylation reaction, consistent
      with the multi-pass ER membrane topology. Duplicate of the accepted core CC term.
    action: ACCEPT
    reason: >-
      Correct core location, consistent with UniProt and the ISS/IEA annotations.
    supported_by:
    - reference_id: file:human/PIGW/PIGW-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  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:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:24367057
  title: Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations
    in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation
    syndrome.
  findings:
  - statement: >-
      First reported patient with PIGW deficiency (GPIBD11): West syndrome with hypsarrhythmia,
      developmental delay, dysmorphic features and hyperphosphatasia, with decreased surface
      expression of GPI-anchored proteins on blood granulocytes; compound heterozygous PIGW variants.
    reference_section_type: ABSTRACT
    supporting_text: >-
      involved in the addition of the acyl-chain to inositol in an early step of GPI
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified case report; establishes the human disease association (GPIBD11) and the
      GPI-AP surface-transport phenotype that underlie the IMP and IC annotations. Abstract-only in
      cache (full_text_available: false).
- id: Reactome:R-HSA-162683
  title: glucosaminyl-PI + fatty acyl-CoA -> glucosaminyl-acyl-PI + CoA-SH
  findings:
  - statement: >-
      Fourth step of GPI synthesis: an acyl group (typically palmitate) is transferred from acyl-CoA
      to glucosaminyl-PI; PIG-W catalyses this reaction.
    supporting_text: >-
      In the fourth step of GPI synthesis, an acyl group (typically palmitate) is transferred from
      acyl CoA to glucosaminyl-PI.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction for the PIGW-catalysed inositol-acylation step; title left exactly as fetched.
- id: Reactome:R-HSA-162710
  title: Synthesis of glycosylphosphatidylinositol (GPI)
  findings:
  - statement: >-
      Human GPI synthesis pathway (nine reactions in the ER); PIGW performs the inositol-acylation
      step within this pathway.
    supporting_text: >-
      GPI is synthesized in the endoplasmic reticulum.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Pathway-level Reactome entry; title left exactly as fetched.
- id: file:human/PIGW/PIGW-uniprot.txt
  title: UniProtKB Q7Z7B1 PIGW record
  findings:
  - statement: >-
      PIGW is an ER multi-pass membrane acyltransferase that acylates the inositol of GlcN-PI at the
      fourth step of GPI-anchor biosynthesis; deficiency causes GPIBD11.
    supporting_text: >-
      participates in the fourth step of GPI-anchor biosynthesis
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Curated UniProt record for the reviewed protein; source of the catalytic activity, subcellular
      location, topology, and disease statements.
core_functions:
- description: >-
    GPI inositol acyltransferase that transfers an acyl group (usually palmitate) from acyl-CoA to
    the 2-OH of the inositol ring of glucosaminyl-phosphatidylinositol (GlcN-PI), forming
    2-acyl-GlcN-PI (GlcN-(acyl)PI) during GPI-anchor biosynthesis in the ER membrane.
  molecular_function:
    id: GO:0032216
    label: glucosaminyl-phosphatidylinositol O-acyltransferase activity
  directly_involved_in:
  - id: GO:0006506
    label: GPI anchor biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/PIGW/PIGW-uniprot.txt
    supporting_text: "Acyltransferase that catalyzes the acyl transfer from an"
  - reference_id: file:human/PIGW/PIGW-uniprot.txt
    supporting_text: "participates in the fourth step of GPI-anchor biosynthesis"
  - reference_id: file:human/PIGW/PIGW-uniprot.txt
    supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []