ArticlePLoS genetics2014
Null mutation in PGAP1 impairing Gpi-anchor maturation in patients with intellectual disability and encephalopathy.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review.Frontiers in neurology · 2021Pooled it
- Mapping the Diverse Genetic Disorders and Rare Diseases Among the Syrian Population: Implications on Refugee Health and Health Services in Host Countries.Journal of immigrant and minority health · 2020Pooled it
- Expanding the genotypic and phenotypic spectrum of PGAP1 deficiency: clinical and functional insights from 15 patients.European journal of human genetics : EJHG · 2026Article
- Biosynthesis of GPI anchored proteins, its deficiencies and treatment.Journal of human genetics · 2025Review
- Prenatal diagnosis using next-generation sequencing in genetic counseling: Novel mutations in three large Iranian families: A case series.International journal of reproductive biomedicine · 2025Article
- Metabolic traits shape responses to LSD1-directed therapy in glioblastoma tumor-initiating cells.Science advances · 2025Article
- Recurrent status epilepticus and severe bifrontal hypometabolism in PGAP1-related neurodevelopmental disorder.Epileptic disorders : international epilepsy journal with videotape · 2025Article
- Fission yeast GPI inositol deacylase Bst1 regulates ER-Golgi transport and functions in late stages of cytokinesis.Molecular biology of the cell · 2025Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis.Nature communications · 2024Article
- Downregulation of lncRNA NEAT1 interacts with miR-374b-5p/PGAP1 axis to aggravate the development of osteoarthritis.Journal of orthopaedic surgery and research · 2023Article
- A point mutation in GPI-attachment signal peptide accelerates the development of prion disease.Acta neuropathologica · 2023Article
- LncRNA LEMD1-AS1 relieves chondrocyte inflammation by targeting miR-944/PGAP1 in osteoarthritis.Cell cycle (Georgetown, Tex.) · 2022Article
- Ethanolamine-phosphate on the second mannose is a preferential bridge for some GPI-anchored proteins.EMBO reports · 2022Article
- Self-incompatibility requires GPI anchor remodeling by the poppy PGAP1 ortholog HLD1.Current biology : CB · 2022Article
- Characterization ofFrontiers in plant science · 2022Article
- Transcriptome sequencing reveals a lncRNA-mRNA interaction network in extramammary Paget's disease.BMC medical genomics · 2021Article
- Calnexin mediates the maturation of GPI-anchors through ER retention.The Journal of biological chemistry · 2020Article
- Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature.Journal of inherited metabolic disease · 2020Review
- The antifungal plant defensin HsAFP1 induces autophagy, vacuolar dysfunction and cell cycle impairment in yeast.Biochimica et biophysica acta. Biomembranes · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many eukaryotic cell-surface proteins are anchored to the membrane via glycosylphosphatidylinositol (GPI). There are at least 26 genes involved in biosynthesis and remodeling of GPI anchors. Hypomorphic coding mutations in seven of these genes have been reported to cause decreased expression of GPI anchored proteins (GPI-APs) on the cell surface and to cause autosomal-recessive forms of intellectual disability (ARID). We performed homozygosity mapping and exome sequencing in a family with encephalopathy and non-specific ARID and identified a homozygous 3 bp deletion (p.Leu197del) in the GPI remodeling gene PGAP1. PGAP1 was not described in association with a human phenotype before. PGAP1 is a deacylase that removes an acyl-chain from the inositol of GPI anchors in the endoplasmic reticulum immediately after attachment of GPI to proteins. In silico prediction and molecular modeling strongly suggested a pathogenic effect of the identified deletion. The expression levels of GPI-APs on B lymphoblastoid cells derived from an affected person were normal. However, when those cells were incubated with phosphatidylinositol-specific phospholipase C (PI-PLC), GPI-APs were cleaved and released from B lymphoblastoid cells from healthy individuals whereas GPI-APs on the cells from the affected person were totally resistant. Transfection with wild type PGAP1 cDNA restored the PI-PLC sensitivity. These results indicate that GPI-APs were expressed with abnormal GPI structure due to a null mutation in the remodeling gene PGAP1. Our results add PGAP1 to the growing list of GPI abnormalities and indicate that not only the cell surface expression levels of GPI-APs but also the fine structure of GPI-anchors is important for the normal neurological development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.