PGAP1

Chr 2AR

post-GPI attachment to proteins inositol deacylase 1

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

NCBI Gene: 80055 ENSG00000197121 UniProt: Q75T13 OMIM: 611655

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene functions early in the glycosylphosphatidylinositol (GPI) biosynthetic pathway, catalyzing the inositol deacylation of GPI. The encoded protein is required for the production of GPI that can attach to proteins, and this may be an important factor in the transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi. Defects in this gene are a cause an autosomal recessive form of cognitive impairment. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.601 OMIM phenotype

Clinical Summary— PGAP1

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Population Constraint (gnomAD)

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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.000

Z-score 3.89

OE 0.42 (0.30–0.60)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.26Z-score

OE missense 0.83 (0.77–0.91)

379 obs / 454.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.30–0.60)

0≤0.351.4

Missense OE?0.83 (0.77–0.91)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

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

This gene — mechanism propensity

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

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.