GPI anchor biosynthesis I — GlcNAc transferase (GPI-GnT) complex; PIGA/PIGC/PIGH/PIGP/PIGQ/PIGY

Glycosylphosphatidylinositol (GPI) anchor biosynthesis begins on the cytoplasmic face of the endoplasmic-reticulum membrane with the transfer of N-acetylglucosamine from UDP-GlcNAc onto phosphatidylinositol (PI) to form GlcNAc-PI, the first and committed step. This reaction is carried out by the multi-subunit GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex, in which PIGA is the catalytic phosphatidylinositol N-acetylglucosaminyltransferase and PIGC, PIGH, PIGP, PIGQ (GPI1) and PIGY are required non-catalytic subunits (the Dol-P-Man synthase subunit DPM2 also associates with and regulates the complex). GPI anchors ultimately tether ~150 human proteins to the cell surface; the GlcNAc-PI product is subsequently de-N-acetylated and elaborated by the downstream Pig/Pgap enzymes. Defects in this first step cause GPI-deficiency disease: acquired somatic PIGA mutations in haematopoietic stem cells cause paroxysmal nocturnal haemoglobinuria (PNH), germline PIGA hypomorphs cause multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2), and biallelic PIGC/PIGH/PIGP/PIGQ/PIGY defects cause inherited GPI-deficiency developmental and epileptic encephalopathies (GPIBD).

MODULE:gpi_anchor_glcnac_transferaseDRAFTMetabolic Pathwaymodules/gpi_anchor_glcnac_transferase.yaml
GPI anchor biosynthetic processGO:0006506
GO:0006506
GPI anchor biosynthetic process
The module is grounded in GPI anchor biosynthetic process (GO:0006506); it covers the first, committed step (GlcNAc-PI synthesis) catalysed by the GPI-GnT complex.
Reactome:R-HSA-162710
Synthesis of glycosylphosphatidylinositol (GPI)
The GlcNAc-PI-forming reaction follows the human Reactome "Synthesis of glycosylphosphatidylinositol (GPI)" sub-pathway (reaction R-HSA-162730).
file:human/PIGA/PIGA-ai-review.yaml
PIGA gene review (human)
The catalytic GlcNAc-transferase step (UniProtKB:P37287, GO:0017176) matches the completed human PIGA review.
file:human/PIGC/PIGC-ai-review.yaml
PIGC gene review (human)
The PIGC accessory-subunit role (UniProtKB:Q92535, GPI-GnT complex GO:0000506) matches the completed human PIGC review.
file:human/PIGH/PIGH-ai-review.yaml
PIGH gene review (human)
The PIGH accessory-subunit role (UniProtKB:Q14442, GPI-GnT complex GO:0000506) matches the completed human PIGH review.
file:human/PIGP/PIGP-ai-review.yaml
PIGP gene review (human)
The PIGP accessory-subunit role (UniProtKB:P57054, GPI-GnT complex GO:0000506) matches the completed human PIGP review.
file:human/PIGQ/PIGQ-ai-review.yaml
PIGQ gene review (human)
The PIGQ/GPI1 stabilising-subunit role (UniProtKB:Q9BRB3, GPI-GnT complex GO:0000506) matches the completed human PIGQ review.
file:human/PIGY/PIGY-ai-review.yaml
PIGY gene review (human)
The PIGY small-subunit role (UniProtKB:Q3MUY2, GPI-GnT complex GO:0000506) matches the completed human PIGY review.
2Nodes
1Parts
0Variant Sets
0Variants
6Annotons
0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gpi_anchor_glcnac_transferase deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 0 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
PIGA P37287 ✓ ✓ ✗
PIGC Q92535 ✓ ✓ ✗
PIGH Q14442 ✓ ✓ ✗
PIGP P57054 ✓ ✓ ✗
PIGQ Q9BRB3 ✓ ✓ ✗
PIGY Q3MUY2 ✓ ✓ ✗

Details

Context
endoplasmic reticulum membraneGO:0005789
GPI anchor biosynthesis, GlcNAc transferase (GPI-GnT) complexMetabolic Pathwaygpi_anchor_glcnac_transferase
GPI anchor biosynthetic processGO:0006506
Context
endoplasmic reticulum membraneGO:0005789

First step of GPI-anchor biosynthesis (GlcNAc-PI synthesis), grounded to the human GPI-GnT complex: catalytic PIGA (UniProtKB:P37287, GO:0017176, EC 2.4.1.198) plus the required non-catalytic subunits PIGC (Q92535), PIGH (Q14442), PIGP (P57054), PIGQ/GPI1 (Q9BRB3) and PIGY (Q3MUY2), all part of the GPI-GnT complex (GO:0000506). The regulatory DPM2 subunit (also a Dol-P-Man synthase subunit) associates with the complex and is reviewed elsewhere. GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; the reaction (R-HSA-162730) and its parent pathway (R-HSA-162710) were verified against the local reactome cache. The step is modelled as a single PROTEIN_COMPLEX node: only PIGA carries a molecular-function term (the catalytic GlcNAc transferase); the accessory subunits are represented by their GPI-anchor-biosynthesis biological-process role (they have no independent catalytic MF — PIGP and PIGY carry the complex activity only with a `contributes_to` qualifier in GOA). Downstream, GlcNAc-PI is de-N-acetylated (PIGL), inositol-acylated (PIGW), mannosylated and EtNP-modified (PIGM/PIGX, PIGV, PIGB, PIGN, PIGO, PIGF, PIGG), then the completed GPI is transferred to protein by the GPI transamidase (PIGK/PIGS/PIGT/PIGU/GPAA1) and remodelled (PGAP1/2/3/…) — separate modules to follow. Disorders: PNH (somatic PIGA), MCAHS2 (germline PIGA), and inherited GPI-deficiency epileptic encephalopathies (PIGC/PIGH/PIGP/PIGQ/PIGY).

Part 1: GlcNAc-PI synthesis (first committed step)
phosphatidylinositol + UDP-GlcNAc to GlcNAc-PIProtein Complexgpi_gnt_step

Annotons

PIGA: catalytic GlcNAc transferase subunit
piga_activity
Participant: Family: PIGA glycosyltransferase family
Family:
PIGA glycosyltransferase familyPANTHER:PTHR45871
Representative Members: PIGA (human)UniProtKB:P37287

Function

phosphatidylinositol N-acetylglucosaminyltransferase activityGO:0017176
Substrates: phosphatidylinositol (PI) UDP-GlcNAc
Products: GlcNAc-PI (N-acetyl-D-glucosaminyl-phosphatidylinositol) UDP

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic subunit of GPI-GnT. Somatic loss = PNH; germline hypomorph = MCAHS2.

PIGC: GPI-GnT accessory subunit
pigc_activity
Participant: Family: PIGC family
Family:
PIGC familyPANTHER:PTHR12982
Representative Members: PIGC (human)UniProtKB:Q92535

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Required accessory subunit of the GPI-GnT complex.

file:human/PIGC/PIGC-ai-review.yaml
required non-catalytic subunit of the GPI-GnT complex (GO:0000506); deficiency = GPIBD16 epileptic encephalopathy
PIGH: GPI-GnT accessory subunit
pigh_activity
Participant: Family: PIGH family
Family:
PIGH familyPANTHER:PTHR15231
Representative Members: PIGH (human)UniProtKB:Q14442

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Required accessory subunit of the GPI-GnT complex.

file:human/PIGH/PIGH-ai-review.yaml
required non-catalytic subunit of the GPI-GnT complex (GO:0000506); deficiency = GPIBD17
PIGP: GPI-GnT accessory subunit
pigp_activity
Participant: Family: PIGP family
Family:
PIGP familyPANTHER:PTHR46346
Representative Members: PIGP (human)UniProtKB:P57054

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Required accessory subunit of the GPI-GnT complex.

file:human/PIGP/PIGP-ai-review.yaml
required small non-catalytic subunit of the GPI-GnT complex (GO:0000506); deficiency = GPIBD
PIGQ: GPI-GnT stabilising subunit (GPI1)
pigq_activity
Participant: Family: PIGQ/GPI1 family
Family:
PIGQ/GPI1 familyPANTHER:PTHR21329
Representative Members: PIGQ (human)UniProtKB:Q9BRB3

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Stabilising accessory subunit (GPI1) of the GPI-GnT complex.

file:human/PIGQ/PIGQ-ai-review.yaml
stabilising non-catalytic subunit (GPI1) of the GPI-GnT complex (GO:0000506); deficiency = GPIBD
PIGY: GPI-GnT small subunit
pigy_activity
Participant: Family: PIGY family
Family:
PIGY familyPANTHER:PTHR39235
Representative Members: PIGY (human)UniProtKB:Q3MUY2

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Small accessory subunit that interacts directly with catalytic PIGA.

file:human/PIGY/PIGY-ai-review.yaml
small non-catalytic subunit interacting directly with PIGA in the GPI-GnT complex (GO:0000506); deficiency = GPIBD