PIGW

Chr 17AR

phosphatidylinositol glycan anchor biosynthesis class W

Also known as: Gwt1, HPMRS5

This gene encodes an inositol acyltransferase that acylates the inositol ring of phosphatidylinositol in the endoplasmic reticulum, a critical step in glycosylphosphatidylinositol (GPI) biosynthesis that anchors cell surface proteins to membranes. Autosomal recessive mutations cause glycosylphosphatidylinositol biosynthesis defect 11, presenting as West syndrome or hyperphosphatasia with mental retardation syndrome. The pathogenic mechanism involves dominant-negative effects that disrupt GPI anchor synthesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 1.071 OMIM phenotype
Clinical SummaryPIGW
🧬
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
127 unique Pathogenic / Likely Pathogenic· 221 VUS of 471 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.35
OE 0.63 (0.391.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.05Z-score
OE missense 0.99 (0.901.10)
256 obs / 258.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.391.07)
00.351.4
Missense OE0.99 (0.901.10)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 10 / 15.8Missense obs/exp: 256 / 258.2Syn Z: -0.46
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPIGW-related hyperphosphatasia with intellectual developmental disorderOTHERAR

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

DN
0.6841th %ile
GOF
0.6248th %ile
LOF
0.2582th %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

471 submitted variants in ClinVar

Classification Summary

Pathogenic112
Likely Pathogenic15
VUS221
Likely Benign106
Benign7
Conflicting8
112
Pathogenic
15
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
107
0
112
Likely Pathogenic
1
1
13
0
15
VUS
28
183
10
0
221
Likely Benign
0
5
0
101
106
Benign
0
2
3
2
7
Conflicting
8
Total29196133103469

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC