PIGY

Chr 4AR

phosphatidylinositol glycan anchor biosynthesis class Y

Also known as: HPMRS6, PIG-Y

NCBI Gene: 84992 ENSG00000255072 UniProt: Q3MUY2 OMIM: 610662

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is part of the GPI-N-acetylglucosaminyltransferase (GIP-GnT) complex which initiates the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is synthesized in the endoplasmic reticulum and serves as an anchor for many surface proteins. Proteins containing GPI anchors can have an important role in cell-cell interactions. The transcript for this gene is bicistronic. The downstream open reading frame encodes this GPI-GnT complex protein, while the upstream open reading frame encodes a protein with unknown function, as represented by GeneID:100996939. [provided by RefSeq, Aug 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.881 OMIM phenotype

Clinical Summary— PIGY

🧬

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.

📋

ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 12 VUS of 22 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?

1.88LOEUF

pLI 0.097

Z-score 0.11

OE 0.89 (0.25–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.15 (0.90–1.49)

41 obs / 35.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.89 (0.25–1.88)

0≤0.351.4

Missense OE?1.15 (0.90–1.49)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 1 / 1.1Missense obs/exp: 41 / 35.6Syn Z: 0.52

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPIGY-related glycosylphosphatidylinositol deficiencyOTHERAR

This gene — mechanism propensity

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

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

22 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS12

Likely Benign4

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	1	0	3
Likely Pathogenic	0	0	0	0	0
VUS	0	12	0	0	12
Likely Benign	0	2	0	2	4
Benign	0	0	2	1	3
Total	1	15	3	3	22

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap PIGY — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →