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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PGAP3
post-GPI attachment to proteins phospholipase 3
Chromosome 17 Β· 17q12
NCBI Gene: 93210Ensembl: ENSG00000161395.14HGNC: HGNC:23719UniProt: A8K0P7
32PubMed Papers
21Diseases
0Drugs
39Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindinghydrolase activity, acting on ester bondsGPI anchor metabolic processGPI anchor biosynthetic processhyperphosphatasia-intellectual disability syndromegenetic disorderasthmacongestive heart failure
✦AI Summary

PGAP3 is a glycosylphosphatidylinositol (GPI) phospholipase involved in the fatty acid remodeling steps of GPI-anchor maturation, where it likely catalyzes the removal of unsaturated acyl chains at sn-2 of inositol phosphate to generate lyso-GPI intermediates 1. This remodeling process is critical for proper integration of GPI-anchored proteins into lipid rafts. PGAP3 is located on chromosome 17-21, a region highly linked to asthma susceptibility 2. The gene shows increased expression in asthmatic airway smooth muscle cells compared to non-asthmatic controls, and when overexpressed, it enhances cell proliferation, contractility, and expression of asthma-associated genes including GATA3 and ALOX5 3. In bronchial epithelial cells, PGAP3 regulates antiviral genes such as RSAD2, OASL, and IFN-Ξ», suggesting a role in respiratory virus responses linked to asthma exacerbations 2. Biallelic pathogenic variants in PGAP3 cause PGAP3-CDG, a congenital disorder of glycosylation characterized by developmental delay, intellectual disability, seizures, hyperphosphatemia, brain malformations, and characteristic facial features 4. The gene also shows co-amplification with ERBB2 in gastric cancer, contributing to tumor progression and poor prognosis 5.

Sources cited
1
PGAP3 is involved in GPI-anchor fatty acid remodeling and is one of 23 novel CDG-associated genes
PMID: 28484880
2
PGAP3 is located on chromosome 17q12-21 linked to asthma and regulates antiviral genes in bronchial epithelial cells
PMID: 39006429
3
PGAP3 is overexpressed in asthmatic airway smooth muscle and enhances proliferation, contractility, and asthma-associated gene expression
PMID: 40131902
4
Biallelic PGAP3 variants cause PGAP3-CDG with developmental delay, intellectual disability, seizures, and other multisystem features
PMID: 37647829
5
PGAP3 co-amplifies with ERBB2 in gastric cancer and contributes to tumor progression and poor prognosis
PMID: 37386793
Disease Associationsβ“˜21
hyperphosphatasia-intellectual disability syndromeOpen Targets
0.70Strong
genetic disorderOpen Targets
0.47Moderate
asthmaOpen Targets
0.40Weak
congestive heart failureOpen Targets
0.21Weak
atrial fibrillationOpen Targets
0.18Weak
alcohol drinkingOpen Targets
0.16Weak
ulcerative colitisOpen Targets
0.13Weak
rheumatoid arthritisOpen Targets
0.13Weak
Crohn's diseaseOpen Targets
0.10Weak
gastric cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
psoriasisOpen Targets
0.07Suggestive
Nasal Cavity PolypOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
autoimmune lymphoproliferative syndromeOpen Targets
0.05Suggestive
autoimmune lymphoproliferative syndrome type 1Open Targets
0.05Suggestive
immunoglobulin A deficiency 2Open Targets
0.05Suggestive
primary biliary cirrhosisOpen Targets
0.05Suggestive
autoimmune diseaseOpen Targets
0.04Suggestive
autoimmune disease, multisystem, infantile-onset, 2Open Targets
0.04Suggestive
Hyperphosphatasia with impaired intellectual development syndrome 4UniProt
Pathogenic Variants39
NM_033419.5(PGAP3):c.914A>G (p.Asp305Gly)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 305
NM_033419.5(PGAP3):c.827C>T (p.Pro276Leu)Pathogenic
not provided|Inborn genetic diseases|Hyperphosphatasia with intellectual disability syndrome 4|PGAP3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 276
NM_033419.5(PGAP3):c.639C>G (p.Tyr213Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 213
NM_033419.5(PGAP3):c.314C>A (p.Pro105Gln)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜…β˜†β˜†2025β†’ Residue 105
NM_033419.5(PGAP3):c.109G>T (p.Glu37Ter)Pathogenic
Inborn genetic diseases|Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 37
NM_033419.5(PGAP3):c.558-10G>APathogenic
Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2025
NM_033419.5(PGAP3):c.320C>T (p.Ser107Leu)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 107
NM_033419.5(PGAP3):c.452dup (p.Trp152fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 152
NM_033419.5(PGAP3):c.851A>G (p.His284Arg)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 284
NM_033419.5(PGAP3):c.694+1G>APathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜…β˜†β˜†2024
NM_033419.5(PGAP3):c.265C>T (p.Gln89Ter)Pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜…β˜†β˜†2024β†’ Residue 89
NM_033419.5(PGAP3):c.850C>T (p.His284Tyr)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜…β˜†β˜†2024β†’ Residue 284
NM_033419.5(PGAP3):c.402dup (p.Met135fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4|not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 135
NM_033419.5(PGAP3):c.186G>A (p.Trp62Ter)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜†β˜†β˜†2025β†’ Residue 62
NM_033419.5(PGAP3):c.355del (p.Leu119fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜†β˜†β˜†2024β†’ Residue 119
NM_033419.5(PGAP3):c.181+1G>TLikely pathogenic
Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜†β˜†β˜†2024
NM_033419.5(PGAP3):c.450dup (p.Phe151fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 151
NM_033419.5(PGAP3):c.739C>T (p.Gln247Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 247
NM_033419.5(PGAP3):c.80dup (p.Val28fs)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 4
β˜…β˜†β˜†β˜†2024β†’ Residue 28
NM_033419.5(PGAP3):c.571C>T (p.Gln191Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 191
View on ClinVar β†—
Related Genes
PIGWProtein interaction99%PGAP1Protein interaction88%GRB7Protein interaction76%STARD3Protein interaction76%MIEN1Protein interaction76%TCAPProtein interaction75%
Tissue Expression6 tissues
Liver
100%
Ovary
59%
Heart
57%
Lung
46%
Bone Marrow
45%
Brain
19%
Gene Interaction Network
Click a node to explore
PGAP3PIGWPGAP1GRB7STARD3MIEN1TCAP
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96FM1
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.15LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.64–1.15]
RankingsWhere PGAP3 stands among ~20K protein-coding genes
  • #11,575of 20,598
    Most Researched32
  • #1,577of 5,498
    Most Pathogenic Variants39
  • #11,935of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedPGAP3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Expanding the phenome and variome of skeletal dysplasia.
PMID: 29620724
Genet Med Β· 2018
1.00
2
PGAP3 regulates human bronchial epithelial cell mRNAs present in asthma and respiratory virus reference data sets.
PMID: 39006429
medRxiv Β· 2024
0.90
3
PGAP3 is expressed at increased levels in asthmatic ASM and is associated with increased ASM proliferation, contractility and expression of GATA3 and ALOX5.
PMID: 40131902
PLoS One Β· 2025
0.80
4
Defining the phenotype of PGAP3-congenital disorder of glycosylation; a review of 65 cases.
PMID: 37647829
Mol Genet Metab Β· 2023
0.70
5
Contribution of PGAP3 co-amplified and co-overexpressed with ERBB2 at 17q12 involved poor prognosis in gastric cancer.
PMID: 37386793
J Cell Mol Med Β· 2023
0.60