PIGO

Chr 9AR

phosphatidylinositol glycan anchor biosynthesis class O

NCBI Gene: 84720ENSG00000165282UniProt: Q8TEQ8OMIM: 614730

The protein transfers ethanolaminephosphate to the third mannose in glycosylphosphatidylinositol (GPI) anchor biosynthesis, which anchors proteins to cell surfaces including blood cells. Autosomal recessive mutations cause hyperphosphatasia with impaired intellectual development syndrome 2. The pathogenic mechanism involves loss of function leading to defective GPI anchor formation.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.811 OMIM phenotype
Clinical Summary— PIGO
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 164 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.50
OE 0.57 (0.41–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.96Z-score
OE missense 0.89 (0.83–0.96)
549 obs / 615.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.41–0.81)
0≤0.351.4
Missense OE0.89 (0.83–0.96)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 23 / 40.1Missense obs/exp: 549 / 615.8Syn Z: -0.94
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePIGO-related hyperphosphatasia with intellectual developmental disorder syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7133th %ile
GOF
0.5760th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic8
VUS164
Likely Benign174
Benign1
37
Pathogenic
8
Likely Pathogenic
164
VUS
174
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
0
9
0
37
Likely Pathogenic
4
1
3
0
8
VUS
1
151
10
2
164
Likely Benign
0
1
44
129
174
Benign
0
1
0
0
1
Total3315466131384

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PIGO · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Two case reports and a literature review of hyperphosphatasia with intellectual disability syndrome 2 caused by a PIGO mutation.
Wang X et al.·Front Pediatr
2025Open AccessReview
Two Different Brain Injury Patterns Associated with Compound Heterozygosis of the PIGO Gene in a Term Newborn: A Case Report.
Dellepiane F et al.·Biomedicines
2024Open AccessCase report
PIGO-CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerations.
Starosta RT et al.·JIMD Rep
2023Open AccessReview
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.
Aguech A et al.·Metab Brain Dis
2023Functional
Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.
Kuwayama R et al.·Nat Commun
2022Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients