PGAP1

Chr 2AR

post-GPI attachment to proteins inositol deacylase 1

Also known as: Bst1, ISPD3024, MRT42, NEDDSBA, SPG67

The protein catalyzes inositol deacylation in the glycosylphosphatidylinositol (GPI) biosynthetic pathway and is required for endoplasmic reticulum-to-Golgi transport of GPI-anchored proteins. Mutations cause autosomal recessive neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities. The gene is highly intolerant to loss-of-function variation (LOEUF 0.6), reflecting its essential role in cellular protein trafficking.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.601 OMIM phenotype
Clinical SummaryPGAP1
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

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 3.89
OE 0.42 (0.300.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.26Z-score
OE missense 0.83 (0.770.91)
379 obs / 454.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.300.60)
00.351.4
Missense OE0.83 (0.770.91)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 22 / 52.4Missense obs/exp: 379 / 454.6Syn Z: 0.80
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPGAP1-related intellectual disability, encephalopathy, impaired GPI-anchor maturationLOFAR

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

DN
0.6355th %ile
GOF
0.4184th %ile
LOF
0.3452th %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

PGAP1 · 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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