PIGW

Chr 17AR

phosphatidylinositol glycan anchor biosynthesis class W

Also known as: Gwt1, HPMRS5

NCBI Gene: 284098ENSG00000277161UniProt: Q7Z7B1

The protein encoded by this gene is an inositol acyltransferase that acylates the inositol ring of phosphatidylinositol. This occurs in the endoplasmic reticulum and is a step in the biosynthesis of glycosylphosphatidylinositol (GPI), which anchors many cell surface proteins to the membrane. Defects in this gene are a cause of the age-dependent epileptic encephalopathy West syndrome as well as a syndrome exhibiting hyperphosphatasia and cognitive disability (HPMRS5). [provided by RefSeq, Jul 2017]

Primary Disease Associations & Inheritance

Glycosylphosphatidylinositol biosynthesis defect 11MIM #616025
AR
466
ClinVar variants
124
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PIGW
🧬
Gene-Disease Validity (ClinGen)
hyperphosphatasia with intellectual disability syndrome 5 · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
124 Pathogenic / Likely Pathogenic· 221 VUS of 466 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.
1.07LOEUF
pLI 0.000
Z-score 1.35
OE 0.63 (0.39–1.07)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.05Z-score
OE missense 0.99 (0.90–1.10)
256 obs / 258.2 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.0.63 (0.39–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.10)
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.1.06
0≤1.21.6
LoF obs/exp: 10 / 15.8Missense obs/exp: 256 / 258.2Syn Z: -0.46

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic110
Likely Pathogenic14
VUS221
Likely Benign106
Benign7
Conflicting8
110
Pathogenic
14
Likely Pathogenic
221
VUS
106
Likely Benign
7
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
105
0
110
Likely Pathogenic
1
0
13
0
14
VUS
16
176
29
0
221
Likely Benign
0
5
0
101
106
Benign
0
2
3
2
7
Conflicting
—8
Total17188150103466

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

View in ClinVar →

Protein Context — Lollipop Plot

PIGW · protein map & ClinVar variants

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

Gene2Phenotype Curations

PIGW-related hyperphosphatasia with intellectual developmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glycosylphosphatidylinositol biosynthesis defect 11

MIM #616025

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
In-Depth Phenotyping of PIGW-Related Disease and Its Role in 17q12 Genomic Disorder.
Feresin A et al.·Biomolecules
2024Case report
PIGW-related glycosylphosphatidylinositol deficiency: A case report and literature review.
Fang Z et al.·Neurol Sci
2024Review
Glycosylphosphatidylinositol Biosynthesis Defect Due To Novel Biallelic Pathogenic Variants in PIGW.
Rabouhi N et al.·Pediatr Neurol
2025
Prenatal ultrasound findings associated with PIGW variants: One more piece in the FRYNS syndrome puzzle? PIGW-related prenatal findings.
Ronzoni L et al.·Prenat Diagn
2022Review
Mutations in the PIGW gene associated with hyperphosphatasia and mental retardation syndrome: a case report.
Fu L et al.·BMC Pediatr
2019Case report
[Genetic analysis of a child with developmental disorder and epilepsy due to a homozygous variant of PIGW gene].
Zeng J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Case report
Prenatal Ultrasound Observations and Postnatal Manifestations Linked to PIGW Variants.
Chen X et al.·Prenat Diagn
2025Case report
PIGW-related glycosylphosphatidylinositol deficiency: Description of a new patient and review of the literature.
Peron A et al.·Am J Med Genet A
2020Case report
Exome sequencing of fetal anomaly syndromes: novel phenotype-genotype discoveries.
Meier N et al.·Eur J Hum Genet
2019
Use of Flow Cytometry for Diagnosis of Epilepsy Associated With Homozygous PIGW Variants.
Foskett GK et al.·Pediatr Neurol
2018Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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