PIGY

Chr 4AR

phosphatidylinositol glycan anchor biosynthesis class Y

Also known as: HPMRS6, PIG-Y

The protein encoded by PIGY is part of the GPI-N-acetylglucosaminyltransferase complex that initiates glycosylphosphatidylinositol (GPI) biosynthesis in the endoplasmic reticulum, where GPI serves as an anchor for many surface proteins involved in cell-cell interactions. Mutations cause hyperphosphatasia with impaired intellectual development syndrome 6 through an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.881 OMIM phenotype
Clinical SummaryPIGY
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Gene-Disease Validity (ClinGen)
hyperphosphatasia with intellectual disability syndrome 6 · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 12 VUS of 46 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.88LOEUF
pLI 0.097
Z-score 0.11
OE 0.89 (0.251.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.32Z-score
OE missense 1.15 (0.901.49)
41 obs / 35.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.89 (0.251.88)
00.351.4
Missense OE1.15 (0.901.49)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 1 / 1.1Missense obs/exp: 41 / 35.6Syn Z: 0.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPIGY-related glycosylphosphatidylinositol deficiencyOTHERAR

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

DN
0.6454th %ile
GOF
0.82top 10%
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

46 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS12
Likely Benign4
Benign3
26
Pathogenic
1
Likely Pathogenic
12
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
24
0
26
Likely Pathogenic
0
0
1
0
1
VUS
0
12
0
0
12
Likely Benign
0
2
0
2
4
Benign
0
0
2
1
3
Total11527346

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

View in ClinVar →

Protein Context — Lollipop Plot

PIGY · 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
PIGY, a new plant envelope-class LTR retrotransposon.
Neumann P et al.·Mol Genet Genomics
2005