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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PIGO
phosphatidylinositol glycan anchor biosynthesis class O
Chromosome 9 Β· 9p13.3
NCBI Gene: 84720Ensembl: ENSG00000165282.17HGNC: HGNC:23215UniProt: Q8TEQ8
35PubMed Papers
21Diseases
0Drugs
81Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mannose-ethanolamine phosphotransferase activityGPI anchor biosynthetic processmembraneendoplasmic reticulum membranehyperphosphatasia-intellectual disability syndromeDisorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylationgenetic disordercomplex neurodevelopmental disorder
✦AI Summary

PIGO (phosphatidylinositol glycan anchor biosynthesis class O) encodes the catalytic subunit of ethanolamine phosphate transferase 3 complex, which catalyzes the tenth and final synthetic step of glycosylphosphatidylinositol (GPI) anchor biosynthesis 1. Specifically, PIGO transfers an ethanolamine phosphate group from phosphatidylethanolamine to the 6-OH position of the third alpha-1,2-linked mannose of the GPI anchor precursor, generating the mature H7 intermediate 2. This modification is essential for proper GPI-anchor attachment to cell surface proteins critical for neuronal and embryonic development 3. PIGO deficiency constitutes a congenital disorder of glycosylation characterized by severe neurological manifestations including intractable epilepsy, severe developmental delay, hypotonia, and ataxia 43. Biochemically, PIGO mutations result in decreased GPI-anchored proteins on blood cells and elevated serum alkaline phosphatase (hyperphosphatasia) 4. Additional features reported include palmoplantar keratoderma and platelet dysfunction 5. Clinically, PIGO-deficient patients present with infantile epileptic encephalopathy and profound developmental delay 3. The condition follows autosomal recessive inheritance, with phenotypic variability ranging from mild to severe presentations 5. PIGO is recognized as a significant genetic cause of hyperphosphatasia with impaired intellectual development syndrome type 2, expanding the spectrum of GPI-anchor deficiency disorders.

Sources cited
1
PIGO identified as one of 29 congenital disorders of glycosylation presenting with cardiometabolic manifestations
PMID: 37239976
2
PIGO functions as catalytic component forming heterodimer with PIGF for ethanolamine phosphate transfer to third mannose of GPI anchor
PMID: 25074286
3
PIGO mutations cause severe infantile epileptic encephalopathy, developmental delay, hypotonia, ataxia and hyperphosphatasia with elevated serum alkaline phosphatase
PMID: 37656370
4
PIGO mutations associated with intractable epilepsy, severe developmental delay, and mild alkaline phosphatase elevation with decreased GPI-anchored proteins on blood cells
PMID: 24417746
5
PIGO deficiency presents with dysmorphism, psychomotor disability, epilepsy, hyperphosphatasemia, and newly reported features including palmoplantar keratoderma and platelet dysfunction
PMID: 28545593
Disease Associationsβ“˜21
hyperphosphatasia-intellectual disability syndromeOpen Targets
0.71Strong
Disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylationOpen Targets
0.50Moderate
genetic disorderOpen Targets
0.42Moderate
complex neurodevelopmental disorderOpen Targets
0.37Weak
Hirschsprung diseaseOpen Targets
0.12Weak
Aganglionic megacolonOpen Targets
0.12Weak
Intellectual disabilityOpen Targets
0.11Weak
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.06Suggestive
Romano-Ward syndromeOpen Targets
0.05Suggestive
Familial short QT syndromeOpen Targets
0.05Suggestive
familial atrial fibrillationOpen Targets
0.05Suggestive
Brugada syndrome 1Open Targets
0.04Suggestive
Idiopathic ventricular fibrillation, not Brugada typeOpen Targets
0.04Suggestive
ventricular fibrillation, paroxysmal familial, type 1Open Targets
0.04Suggestive
catecholaminergic polymorphic ventricular tachycardia 4Open Targets
0.04Suggestive
catecholaminergic polymorphic ventricular tachycardia 1Open Targets
0.04Suggestive
Brugada syndromeOpen Targets
0.04Suggestive
long QT syndrome 5Open Targets
0.04Suggestive
sinoatrial node dysfunction and deafnessOpen Targets
0.04Suggestive
short QT syndrome type 2Open Targets
0.04Suggestive
Hyperphosphatasia with impaired intellectual development syndrome 2UniProt
Pathogenic Variants81
NM_032634.4(PIGO):c.2557G>T (p.Glu853Ter)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 853
NM_032634.4(PIGO):c.2191dup (p.Arg731fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 731
NM_032634.3(PIGO):c.3069+5G>APathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2025
NM_032634.4(PIGO):c.1810dup (p.Arg604fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|Hyperphosphatasia-intellectual disability syndrome|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 604
NM_032634.4(PIGO):c.355C>T (p.Arg119Trp)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 119
NM_032634.4(PIGO):c.364C>T (p.Arg122Ter)Pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 122
NM_032634.4(PIGO):c.511G>T (p.Gly171Ter)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 171
NM_032634.4(PIGO):c.589_590del (p.Pro197fs)Pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 197
NM_032634.4(PIGO):c.1549del (p.Ala517fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 517
NM_032634.4(PIGO):c.2361dup (p.Thr788fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 788
NM_032634.4(PIGO):c.2869C>T (p.Leu957Phe)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2023β†’ Residue 957
NM_032634.4(PIGO):c.1271_1272del (p.Val424fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 424
NM_032634.4(PIGO):c.2404C>T (p.Arg802Ter)Pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2022β†’ Residue 802
NM_032634.4(PIGO):c.3069+2T>CLikely pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2020
NM_032634.4(PIGO):c.2648-1G>ALikely pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜…β˜†β˜†2017
NM_032634.4(PIGO):c.511_511+1delinsTTLikely pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜†β˜†β˜†2026
NM_032634.4(PIGO):c.1052dup (p.Gly351_Glu352insTer)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜†β˜†β˜†2025β†’ Residue 351
NM_032634.4(PIGO):c.2037_2062del (p.Leu680fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜†β˜†β˜†2025β†’ Residue 680
NM_032634.4(PIGO):c.1445_1449del (p.Leu482fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜†β˜†β˜†2025β†’ Residue 482
NM_032634.4(PIGO):c.28del (p.Leu10fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 2
β˜…β˜†β˜†β˜†2025β†’ Residue 10
View on ClinVar β†—
Related Genes
PIGNShared pathway100%PIGGShared pathway100%PIGXShared pathway100%CWH43Shared pathway100%PGAP4Shared pathway100%PIGYProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Liver
85%
Lung
67%
Bone Marrow
60%
Brain
58%
Heart
46%
Gene Interaction Network
Click a node to explore
PIGOPIGNPIGGPIGXCWH43PGAP4PIGY
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8TEQ8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.89LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.59–0.89]
RankingsWhere PIGO stands among ~20K protein-coding genes
  • #11,033of 20,598
    Most Researched35
  • #925of 5,498
    Most Pathogenic Variants81 Β· top quartile
  • #7,979of 17,882
    Most Constrained (LOEUF)0.89
Genes detectedPIGO
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
PMID: 37239976
Int J Mol Sci Β· 2023
1.00
2
Phenytoin-induced gingival overgrowth.
PMID: 21651505
Acta Neurol Scand Β· 2012
0.90
3
PIGO deficiency: palmoplantar keratoderma and novel mutations.
PMID: 28545593
Orphanet J Rare Dis Β· 2017
0.80
4
A novel homozygous PIGO mutation associated with severe infantile epileptic encephalopathy, profound developmental delay and psychomotor retardation: structural and 3D modelling investigations and genotype-phenotype correlation.
PMID: 37656370
Metab Brain Dis Β· 2023
0.70
5
Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175.
PMID: 39856101
NPJ Parkinsons Dis Β· 2025
0.60