PIGO

Chr 9AR

phosphatidylinositol glycan anchor biosynthesis class O

Also known as: HPMRS2, hGPCR43

NCBI Gene: 84720ENSG00000165282UniProt: Q8TEQ8

This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This protein is involved in the transfer of ethanolaminephosphate (EtNP) to the third mannose in GPI. At least three alternatively spliced transcripts encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

Hyperphosphatasia with impaired intellectual development syndrome 2MIM #614749
AR
1148
ClinVar variants
44
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PIGO
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 223 VUS of 1148 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.81LOEUF
pLI 0.000
Z-score 2.50
OE 0.57 (0.41–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.96Z-score
OE missense 0.89 (0.83–0.96)
549 obs / 615.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.41–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.83–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 23 / 40.1Missense obs/exp: 549 / 615.8Syn Z: -0.94

ClinVar Variant Classifications

1148 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic4
VUS223
Likely Benign226
Benign5
Conflicting2
40
Pathogenic
4
Likely Pathogenic
223
VUS
226
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
25
0
40
Likely Pathogenic
2
1
1
0
4
VUS
1
201
17
4
223
Likely Benign
0
2
56
168
226
Benign
0
1
3
1
5
Conflicting
—2
Total18205102173500

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.

Gene2Phenotype Curations

PIGO-related hyperphosphatasia with intellectual developmental disorder syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperphosphatasia with impaired intellectual development syndrome 2

MIM #614749

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
PIGO deficiency: palmoplantar keratoderma and novel mutations.
Morren MA et al.·Orphanet J Rare Dis
2017Review
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
Phenotype-genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties.
Tanigawa J et al.·Hum Mutat
2017
PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels.
Nakamura K et al.·Epilepsia
2014Case report
Comprehensive analysis of alternative splicing across multiple transcriptomic cohorts reveals prognostic signatures in prostate cancer.
Mou Z et al.·Hum Genomics
2023Cohort
A homozygous PIGO mutation associated with severe infantile epileptic encephalopathy and corpus callosum hypoplasia, but normal alkaline phosphatase levels.
Zehavi Y et al.·Metab Brain Dis
2017Case report
Phenytoin-induced gingival overgrowth management with periodontal treatment.
Gurgel BC et al.·Braz Dent J
2015Case report
Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures: Expanding the Phenotype.
Record CJ et al.·Ann Neurol
2025
High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency.
Tanigawa J et al.·Brain Dev
2021Clinical trial
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools