PIGN

Chr 18AR

phosphatidylinositol glycan anchor biosynthesis class N

The protein transfers phosphoethanolamine to the first mannose of the GPI anchor during GPI-anchor biosynthesis in the endoplasmic reticulum, which is essential for anchoring proteins to cell surfaces. Autosomal recessive mutations cause multiple congenital anomalies-hypotonia-seizures syndrome 1. The pathogenic mechanism involves defective GPI anchor synthesis, which disrupts normal protein anchoring to cell membranes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.021 OMIM phenotype
Clinical SummaryPIGN
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Gene-Disease Validity (ClinGen)
multiple congenital anomalies-hypotonia-seizures syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.41
OE 0.78 (0.601.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.42Z-score
OE missense 0.94 (0.871.02)
412 obs / 436.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.601.02)
00.351.4
Missense OE0.94 (0.871.02)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 38 / 48.6Missense obs/exp: 412 / 436.4Syn Z: -0.35
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePIGN-related multiple congenital anomalies-hypotonia-seizures syndromeLOFAR

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

DN
0.6551th %ile
GOF
0.5366th %ile
LOF
0.3941th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PIGN · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗