PGAP3

Chr 17AR

post-GPI attachment to proteins phospholipase 3

Also known as: AGLA546, CAB2, PERLD1, PP1498, hCOS16

This gene encodes a GPI-specific phospholipase that removes unsaturated fatty acids from GPI anchors in the Golgi apparatus, which is critical for proper integration of GPI-anchored proteins into lipid rafts. Mutations cause hyperphosphatasia with impaired intellectual development syndrome 4, an autosomal recessive disorder characterized by cognitive disability and elevated alkaline phosphatase levels. The gene shows tolerance to loss-of-function variants (pLI 0.002, LOEUF 0.83), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.831 OMIM phenotype
Clinical SummaryPGAP3
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Gene-Disease Validity (ClinGen)
hyperphosphatasia with intellectual disability syndrome 4 · 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
0.83LOEUF
pLI 0.002
Z-score 2.05
OE 0.44 (0.250.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.69Z-score
OE missense 0.86 (0.750.98)
154 obs / 179.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.250.83)
00.351.4
Missense OE0.86 (0.750.98)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 7 / 15.8Missense obs/exp: 154 / 179.9Syn Z: 0.67
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePGAP3-related hyperphosphatasia with intellectual developmental disorder syndromeLOFAR

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

DN
0.7326th %ile
GOF
0.7126th %ile
LOF
0.2288th %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

PGAP3 · 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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