GPI anchor biosynthesis II — de-N-acetylation, inositol acylation and mannosylation; PIGL/PIGW/PIGM/PIGX/PIGV/PIGB

After the GPI-GlcNAc transferase complex makes GlcNAc-PI, the glycosylphosphatidylinositol (GPI) precursor is elaborated by de-N-acetylation, inositol acylation and the sequential addition of three mannoses, on the endoplasmic-reticulum membrane. PIGL de-N-acetylates GlcNAc-PI to glucosaminyl-phosphatidylinositol (GlcN-PI); the intermediate is then flipped to the ER lumen and PIGW acylates the inositol ring (from acyl-CoA) to GlcN-(acyl)PI, a form required for later transamidase recognition. Three dolichyl-phosphate-mannose (Dol-P-Man)- dependent mannosyltransferases then build the trimannosyl core: GPI mannosyltransferase I (the catalytic PIGM with its stabilising subunit PIGX) adds the first mannose (alpha-1,4); PIGV (GPI-MT-II) adds the second (alpha-1,6); and PIGB (GPI-MT-III) adds the third (alpha-1,2), the mannose that later receives the bridging ethanolamine-phosphate for protein attachment. Defects across this segment cause GPI-deficiency disease: PIGL (CHIME syndrome), PIGW and PIGM/PIGV (hyperphosphatasia with mental retardation / Mabry syndrome and related inherited GPI-deficiency encephalopathies), and PIGB (a developmental and epileptic encephalopathy, GPIBD).

MODULE:gpi_anchor_core_glycan_assemblyDRAFTMetabolic Pathwaymodules/gpi_anchor_core_glycan_assembly.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 de-N-acetylation, inositol-acylation and trimannosylation of the GPI precursor.
Reactome:R-HSA-162710
Synthesis of glycosylphosphatidylinositol (GPI)
Step order and intermediates follow the human Reactome "Synthesis of glycosylphosphatidylinositol (GPI)" sub-pathway (reactions R-HSA-162857/162683/162830/162873/162821).
file:human/PIGL/PIGL-ai-review.yaml
PIGL gene review (human)
The GlcNAc-PI de-N-acetylation step (UniProtKB:Q9Y2B2, GO:0000225) matches the completed human PIGL review.
file:human/PIGW/PIGW-ai-review.yaml
PIGW gene review (human)
The inositol-acylation step (UniProtKB:Q7Z7B1, GO:0032216) matches the completed human PIGW review.
file:human/PIGM/PIGM-ai-review.yaml
PIGM gene review (human)
The first-mannose (alpha-1,4) step (UniProtKB:Q9H3S5, GO:0180041) matches the completed human PIGM review.
file:human/PIGX/PIGX-ai-review.yaml
PIGX gene review (human)
The GPI-MT-I stabilising-subunit role (UniProtKB:Q8TBF5, GPI-MT-I complex GO:1990529) matches the completed human PIGX review.
file:human/PIGV/PIGV-ai-review.yaml
PIGV gene review (human)
The second-mannose (alpha-1,6) step (UniProtKB:Q9NUD9, GO:0120563) matches the completed human PIGV review.
file:human/PIGB/PIGB-ai-review.yaml
PIGB gene review (human)
The third-mannose (alpha-1,2) step (UniProtKB:Q92521, GO:0120564) matches the completed human PIGB review.
6Nodes
5Parts
0Variant Sets
0Variants
6Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gpi_anchor_core_glycan_assembly 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.

Function consistency and core coverage

5 gene-function check(s) reflected in core functions · 0 conflict(s) · 5 evidence or coverage gap(s) (10 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
pigl_activity PIGL (human)
UniProtKB:Q9Y2B2
Family Representative 		N-acetylglucosaminylphosphatidylinositol deacetylase activity
GO:0000225 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pigw_activity PIGW (human)
UniProtKB:Q7Z7B1
Family Representative 		glucosaminyl-phosphatidylinositol O-acyltransferase activity
GO:0032216 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pigm_activity PIGM (human)
UniProtKB:Q9H3S5
Family Representative 		dol-P-Man:GlcN-acyl-PI alpha-1,4-mannosyltransferase activity
GO:0180041 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pigv_activity PIGV (human)
UniProtKB:Q9NUD9
Family Representative 		dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activity
GO:0120563 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pigb_activity PIGB (human)
UniProtKB:Q92521
Family Representative 		dol-P-Man:Man(2)GlcN-acyl-PI alpha-1,2-mannosyltransferase activity
GO:0120564 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pigl_activity PIGL de-N-acetylase family
PANTHER:PTHR12993
Family 		N-acetylglucosaminylphosphatidylinositol deacetylase activity
GO:0000225 		Family Scope Restricted
GO:0016811 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Amide-hydrolase activity is established for the deacetylase subfamilies but not for the SF29 GalB hydratase lineage.
pigw_activity PIGW inositol-acyltransferase family
PANTHER:PTHR20661
Family 		glucosaminyl-phosphatidylinositol O-acyltransferase activity
GO:0032216 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR20661.
pigm_activity GPI mannosyltransferase I family (PIGM)
PANTHER:PTHR12886
Family 		dol-P-Man:GlcN-acyl-PI alpha-1,4-mannosyltransferase activity
GO:0180041 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12886.
pigv_activity GPI mannosyltransferase II family (PIGV)
PANTHER:PTHR12468
Family 		dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activity
GO:0120563 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12468.
pigb_activity GPI mannosyltransferase III family (PIGB)
PANTHER:PTHR22760
Family 		dol-P-Man:Man(2)GlcN-acyl-PI alpha-1,2-mannosyltransferase activity
GO:0120564 		Family Scope Restricted
GO:0120564 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. PIGB/GPI10 (SF4), as gpi_anchor_core_glycan_assembly asserts on the base family.

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
PIGB Q92521 ✓ ✓ ✗
PIGL Q9Y2B2 ✓ ✓ ✗
PIGM Q9H3S5 ✓ ✓ ✗
PIGV Q9NUD9 ✓ ✓ ✗
PIGW Q7Z7B1 ✓ ✓ ✗
PIGX Q8TBF5 ✓ ✓ ✗

Details

Context
endoplasmic reticulum membraneGO:0005789
GPI anchor core glycan assembly (de-N-acetylation, inositol acylation, mannosylation)Metabolic Pathwaygpi_anchor_core_glycan_assembly
GPI anchor biosynthetic processGO:0006506
Context
endoplasmic reticulum membraneGO:0005789

GPI core-glycan-assembly segment, grounded to the human enzymes PIGL (UniProtKB:Q9Y2B2, GO:0000225, EC 3.5.1.89), PIGW (Q7Z7B1, GO:0032216), the GPI-MT-I complex (catalytic PIGM Q9H3S5 GO:0180041 + stabilising PIGX Q8TBF5; complex GO:1990529), PIGV (Q9NUD9, GO:0120563) and PIGB (Q92521, GO:0120564). GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; Reactome reaction ids/titles were verified against the local reactome cache. Each step uses a PANTHER family selector with the human enzyme as representative; GPI-MT-I is a PROTEIN_COMPLEX node (PIGM catalytic + PIGX stabiliser, the latter modelled by its BP role as it has no catalytic MF). The three mannosyltransferases are Dol-P-Man-dependent (donor supplied by the DPM1/2/3 module). Note the pathway interleaves with the ethanolamine-phosphate additions: PIGN adds EtNP to the first mannose between the PIGM and PIGV steps (covered in the GPI EtNP module), and PIGO/PIGG add EtNP to the third/second mannoses after PIGB. Upstream is the GPI-GnT module (GlcNAc-PI); downstream the EtNP-modified Man3 GPI is transferred to protein by the GPI transamidase (PIGK/PIGS/PIGT/ PIGU/GPAA1) and remodelled (PGAP1/2/3) — separate modules. Disorders: CHIME syndrome (PIGL), GPIBD/hyperphosphatasia (PIGW), GPI-deficiency with thrombosis/seizures (PIGM), Mabry syndrome (PIGV), GPIBD encephalopathy (PIGB).

Connections

pigl_step -> pigw_step Provides Input For
GlcN-PI from PIGL is inositol-acylated by PIGW.
pigw_step -> gpi_mt1_step Provides Input For
GlcN-(acyl)PI from PIGW receives the first mannose from GPI-MT-I (PIGM/PIGX).
gpi_mt1_step -> pigv_step Provides Input For
Man1-GlcN-(acyl)PI (after EtNP addition to Man1 by PIGN) receives the second mannose from PIGV.
pigv_step -> pigb_step Provides Input For
Man2-GlcN-(acyl)PI receives the third mannose from PIGB.
Part 1: de-N-acetylation (GlcNAc-PI to GlcN-PI)
GlcNAc-PI to glucosaminyl-PI (GlcN-PI)Reactionpigl_step

Annotons

PIGL: GlcNAc-PI de-N-acetylase
pigl_activity
Participant: Family: PIGL de-N-acetylase family
Family:
PIGL de-N-acetylase familyPANTHER:PTHR12993
Representative Members: PIGL (human)UniProtKB:Q9Y2B2

Function

N-acetylglucosaminylphosphatidylinositol deacetylase activityGO:0000225
Substrates: GlcNAc-PI H2O
Products: GlcN-PI (glucosaminyl-PI) acetate

Locations

endoplasmic reticulum membraneGO:0005789

De-N-acetylates GlcNAc-PI; deficiency = CHIME syndrome.

Part 2: inositol acylation
GlcN-PI to GlcN-(acyl)PIReactionpigw_step

Annotons

PIGW: GPI inositol acyltransferase
pigw_activity
Participant: Family: PIGW inositol-acyltransferase family
Family:
PIGW inositol-acyltransferase familyPANTHER:PTHR20661
Representative Members: PIGW (human)UniProtKB:Q7Z7B1

Function

glucosaminyl-phosphatidylinositol O-acyltransferase activityGO:0032216
Substrates: GlcN-PI fatty acyl-CoA (usually palmitoyl-CoA)
Products: GlcN-(acyl)PI CoA

Locations

endoplasmic reticulum membraneGO:0005789

Inositol acylation; deficiency = GPIBD (hyperphosphatasia/epilepsy).

Part 3: first mannose (alpha-1,4) — GPI-MT-I complex
GlcN-(acyl)PI to Man1-GlcN-(acyl)PIProtein Complexgpi_mt1_step

Annotons

PIGM: GPI mannosyltransferase I (catalytic)
pigm_activity
Participant: Family: GPI mannosyltransferase I family (PIGM)
Family:
GPI mannosyltransferase I family (PIGM)PANTHER:PTHR12886
Representative Members: PIGM (human)UniProtKB:Q9H3S5

Function

dol-P-Man:GlcN-acyl-PI alpha-1,4-mannosyltransferase activityGO:0180041
Substrates: GlcN-(acyl)PI dolichyl-phosphate-mannose (Dol-P-Man)
Products: Man1-GlcN-(acyl)PI dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic subunit of GPI mannosyltransferase I.

PIGX: GPI-MT-I stabilising subunit
pigx_activity
Participant: Family: PIGX family
Family:
PIGX familyPANTHER:PTHR28650
Representative Members: PIGX (human)UniProtKB:Q8TBF5

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Stabilises catalytic PIGM in the GPI-MT-I complex.

file:human/PIGX/PIGX-ai-review.yaml
non-catalytic stabilising subunit of GPI-MT-I (GO:1990529) that binds and protects catalytic PIGM
Part 4: second mannose (alpha-1,6)
Man1-GlcN-(acyl)PI to Man2-GlcN-(acyl)PIReactionpigv_step

Annotons

PIGV: GPI mannosyltransferase II
pigv_activity
Participant: Family: GPI mannosyltransferase II family (PIGV)
Family:
GPI mannosyltransferase II family (PIGV)PANTHER:PTHR12468
Representative Members: PIGV (human)UniProtKB:Q9NUD9

Function

dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activityGO:0120563
Substrates: Man1-GlcN-(acyl)PI (EtNP-modified on Man1 by PIGN) dolichyl-phosphate-mannose (Dol-P-Man)
Products: Man2-GlcN-(acyl)PI dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

Adds the second mannose. (The first mannose receives an EtNP from PIGN before this step — see the GPI ethanolamine-phosphate module.)

Part 5: third mannose (alpha-1,2)
Man2-GlcN-(acyl)PI to Man3-GlcN-(acyl)PIReactionpigb_step

Annotons

PIGB: GPI mannosyltransferase III
pigb_activity
Participant: Family: GPI mannosyltransferase III family (PIGB)
Family:
GPI mannosyltransferase III family (PIGB)PANTHER:PTHR22760
Representative Members: PIGB (human)UniProtKB:Q92521

Function

dol-P-Man:Man(2)GlcN-acyl-PI alpha-1,2-mannosyltransferase activityGO:0120564
Substrates: Man2-GlcN-(acyl)PI dolichyl-phosphate-mannose (Dol-P-Man)
Products: Man3-GlcN-(acyl)PI dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

Adds the third mannose, which receives the protein-bridging EtNP (via PIGO) in the next module.