Affinage

PIGA

Phosphatidylinositol N-acetylglucosaminyltransferase subunit A · UniProt P37287

Length
484 aa
Mass
54.1 kDa
Annotated
2026-06-10
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIGA encodes the catalytic subunit of the GPI-GlcNAc transferase complex that executes the first committed step of glycosylphosphatidylinositol (GPI) anchor biosynthesis—the transfer of N-acetylglucosamine from UDP-GlcNAc to phosphatidylinositol to form GlcNAc-PI (PMID:7680492, PMID:9463366). The protein is an ER transmembrane enzyme with a large cytoplasmic domain homologous to bacterial GlcNAc transferases and a small lumenal domain required for rough-ER targeting; catalysis occurs on the cytoplasmic face of the ER membrane (PMID:8900170). PIGA acts within a four-subunit complex with PIG-H, PIG-C, and hGPI1, which reconstitutes GPI-GnT activity in vitro and discriminates between phosphatidylinositol species by recognizing the fatty acyl chains of the substrate (PMID:8900170, PMID:9463366). This activity is conserved and essential, as the yeast ortholog GPI3 is required for vegetative growth and GlcNAc-PI synthesis (PMID:7768896). Loss of PIGA abolishes surface display of all GPI-anchored proteins: somatic mutation in hematopoietic cells causes paroxysmal nocturnal hemoglobinuria (PNH), with rescue by wild-type cDNA restoring GPI-linked protein expression (PMID:8306954), while hypomorphic germline alleles that retain partial enzymatic activity cause early-onset epileptic encephalopathy, with residual activity correlating with clinical severity (PMID:22305531, PMID:24706016). The functional consequences of GPI deficiency include heightened complement-mediated lysis of affected cells (PMID:10556176, PMID:28441409), evasion of NK-cell killing through loss of the GPI-anchored NKG2D ligands ULBP1 and ULBP2 (PMID:16195329), impaired BMP4 signaling from absence of GPI-anchored co-receptors during stem-cell differentiation (PMID:18397754), and defective neuronal differentiation (PMID:28441409). Notably, PIGA loss alone is insufficient to drive clonal expansion in PNH (PMID:9276719, PMID:10556176) and does not directly confer apoptosis resistance (PMID:9746796).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Established that PIGA is required for the first intermediate of GPI-anchor biosynthesis, defining its position at the head of the pathway.

    Evidence cDNA cloning and functional complementation of GPI-deficient cell lines

    PMID:7680492

    Open questions at the time
    • Did not resolve whether PIGA is the catalytic subunit or a cofactor
    • No subunit composition of the responsible enzyme
  2. 1994 High

    Identified PIGA as the causative gene of PNH by linking somatic mutations to loss of GPI-anchored proteins and rescuing the defect with wild-type cDNA.

    Evidence Transcript sequencing and complementation transfection in patient B-lymphoblastoid lines

    PMID:8306954

    Open questions at the time
    • Did not explain why PIGA-mutant clones expand in PNH
    • Mechanism of disease phenotype beyond GPI loss unaddressed
  3. 1995 High

    Demonstrated that the enzymatic role and essentiality of PIGA are conserved through the yeast ortholog GPI3.

    Evidence Temperature-sensitive mutants, in vitro inositol incorporation, and gene disruption in S. cerevisiae

    PMID:7768896

    Open questions at the time
    • Did not define the multi-subunit nature of the mammalian enzyme
  4. 1996 High

    Defined the topology of PIGA as an ER transmembrane protein catalyzing on the cytoplasmic face, with a lumenal domain for ER targeting and physical association with PIG-H.

    Evidence Co-IP, subcellular fractionation, and domain mutagenesis

    PMID:8900170

    Open questions at the time
    • Full subunit composition not yet established
    • No structural model of the active site
  5. 1998 High

    Reconstituted the four-subunit GPI-GnT complex (PIG-A, PIG-H, PIG-C, hGPI1) and showed it recognizes PI fatty acyl chains, establishing substrate selectivity and complex boundaries.

    Evidence Co-IP, in vitro GlcNAc transferase activity, and PI species substrate assays

    PMID:9463366

    Open questions at the time
    • Did not assign individual catalytic versus regulatory roles to each subunit
    • No atomic structure of the complex
  6. 1997 Medium

    Connected GPI synthesis to secretory trafficking by showing ortholog loss retards ER exit of GPI-dependent cell wall proteins.

    Evidence Yeast cwh6/gpi3 conditional mutant trafficking and ER morphology analysis

    PMID:9079905

    Open questions at the time
    • Ortholog system; mammalian trafficking consequences not directly tested
  7. 1999 High

    Showed that Piga loss alone is insufficient to drive PNH clonal expansion, separating the enzymatic defect from clonal selection.

    Evidence Cre/loxP conditional and ES knockout mouse models with longitudinal monitoring and complement sensitivity assays

    PMID:10377440 PMID:10556176 PMID:9276719

    Open questions at the time
    • The additional factor(s) required for clonal expansion remain unidentified
    • Tissue-specific GPI requirement mechanisms not resolved
  8. 2002 Medium

    Linked GPI deficiency to immune evasion, showing PIGA-mutant cells resist perforin-dependent NK killing due to loss of a GPI-anchored NK-activating ligand.

    Evidence 51Cr-release NK cytotoxicity with PIGA rescue and perforin-pathway inhibitors

    PMID:12130519

    Open questions at the time
    • Specific ligand not yet identified in this study
    • Single lab
  9. 2005 Medium

    Identified the GPI-anchored NKG2D ligands ULBP1 and ULBP2 as the missing activators responsible for NK evasion in PIGA-deficient cells.

    Evidence NK cytotoxicity with anti-ULBP and anti-NKG2D antibody blocking

    PMID:16195329

    Open questions at the time
    • In vivo relevance to PNH clonal selection not established
    • Single lab
  10. 2008 Medium

    Showed GPI deficiency impairs developmental signaling, blocking trophoblast differentiation via loss of GPI-anchored BMP co-receptors.

    Evidence PIGA-null hES clones with BMP4 differentiation and signaling assays

    PMID:18397754

    Open questions at the time
    • Identity of the specific GPI-anchored BMP co-receptor not defined
    • Single lab, two clones
  11. 2012 Medium

    Established a germline hypomorphic-allele paradigm by showing PIGA p.Arg412* retains partial GPI biosynthetic activity.

    Evidence Transfection complementation in PIGA-null cells with flow cytometry

    PMID:22305531

    Open questions at the time
    • Genotype-phenotype relationship across the allelic spectrum not yet defined
    • Single lab
  12. 2014 Medium

    Demonstrated that germline PIGA hypomorphic alleles cause epileptic encephalopathy with residual activity correlating with clinical severity, and characterized alternative translation initiation rescuing function.

    Evidence Complementation assays of multiple alleles in PIGA-null JY5 cells with surface GPI-anchored protein readouts

    PMID:24357517 PMID:24706016

    Open questions at the time
    • Mechanistic basis of neurological phenotype not directly addressed
    • Single lab
  13. 2017 Medium

    Provided cellular mechanism for the neurological disease by showing a hypomorphic PIGA mutation impairs neuronal differentiation and complement regulation in iPSC-derived neural progenitors.

    Evidence Patient-mutation iPSC neural differentiation, electrophysiology, and complement cytotoxicity assays

    PMID:28441409

    Open questions at the time
    • Which GPI-anchored neuronal proteins mediate the defect not identified
    • Single lab
  14. 2020 Medium

    Validated the catalytic subunit as a small-molecule target by showing jawsamycin selectively inhibits the fungal GPI3/PIG-A ortholog over human PIG-A.

    Evidence Yeast reporter screen, antifungal assays, genetic target identification, and mouse model

    PMID:32636417

    Open questions at the time
    • Human PIG-A inhibitor selectivity window not exploited therapeutically
    • Structural basis of selectivity unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular factor(s) beyond PIGA loss that confer clonal proliferative advantage in PNH, and the atomic structure of the GPI-GnT complex active site, remain undefined.
  • No identified second-hit driver of PNH clonal expansion
  • No high-resolution structure of the four-subunit complex
  • Individual subunit catalytic versus regulatory roles not fully assigned

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-392499 Metabolism of proteins 2
Partners
GPI1PIGCPIGH
Complex memberships
GPI-GlcNAc transferase (GPI-GnT) complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 PIG-A encodes a protein necessary for the synthesis of N-acetylglucosaminyl-phosphatidylinositol (GlcNAc-PI), the first intermediate in GPI-anchor biosynthesis; complementation of GPI-anchor-deficient cells with PIG-A cDNA restored GPI-anchor synthesis. cDNA cloning, functional complementation of GPI-deficient cell lines Science High 7680492
1996 PIG-A is an endoplasmic reticulum transmembrane protein with a large cytoplasmic domain homologous to bacterial GlcNAc transferases and a small lumenal domain; PIG-H is a cytoplasmically oriented ER-associated protein; PIG-A and PIG-H form a protein complex in the ER. The small lumenal domain of PIG-A plays an essential functional role in targeting to the rough ER. GlcNAc transfer to PI occurs on the cytoplasmic face of the ER. Co-immunoprecipitation, subcellular fractionation, domain deletion/mutagenesis, ER targeting assays The Journal of Biological Chemistry High 8900170
1998 The first step of GPI biosynthesis (transfer of GlcNAc from UDP-GlcNAc to PI) is catalyzed by a complex of four mammalian proteins—PIG-A, PIG-H, PIG-C, and hGPI1—resident in the ER membrane. The reconstituted complex had GPI-GlcNAc transferase (GPI-GnT) activity in vitro but did not catalyze the second reaction. Bovine PI was utilized ~100-fold more efficiently than soybean PI, indicating that the complex recognizes fatty acyl chains of PI. PIG-L (involved in step 2) did not associate with the isolated complex. Co-immunoprecipitation, in vitro GlcNAc transferase activity assay, substrate specificity assay with different PI species The EMBO Journal High 9463366
1994 Somatic mutations in PIG-A (frameshift, missense, nonsense, splice site) in hematopoietic cells cause paroxysmal nocturnal hemoglobinuria (PNH); transfection of wild-type PIG-A cDNA into EBV-transformed B-lymphoblastoid cell lines from PNH patients fully restored GPI-linked protein surface expression, proving PIG-A is the causative gene. RT-PCR/sequencing of PIG-A transcripts, functional complementation transfection assay, flow cytometry The EMBO Journal High 8306954
1995 The yeast GPI3 gene (ortholog of mammalian PIG-A) encodes a protein required for GlcNAc-PI synthesis (first step of GPI anchor biosynthesis); gpi3 mutants lack in vitro GlcNAc-PI synthetic activity; GPI3 is essential for vegetative growth in yeast. Temperature-sensitive mutant isolation, in vitro [3H]-inositol incorporation assay, gene disruption, genetic complementation The Journal of Biological Chemistry High 7768896
1997 Pig-a gene inactivation in mouse embryonic stem cells by homologous recombination produced cells competent for hematopoiesis with the PNH phenotype, but pig-a inactivation alone did not confer a proliferative advantage to hematopoietic stem cells, demonstrating that additional factors are required for PNH clone expansion. Homologous recombination (gene knockout) in murine ES cells, chimera generation, flow cytometry The Journal of Clinical Investigation High 9276719
1999 Cre/loxP-mediated inactivation of Piga in mosaic mice showed that PIGA(-) blood cells are more sensitive to complement-mediated lysis and have a decreased lifespan in circulation, but the PIGA(-) cell population did not expand over 12 months, confirming that Piga mutation alone is insufficient to cause PNH. Cre/loxP conditional knockout, flow cytometry, complement sensitivity assay, longitudinal monitoring Blood High 10556176
1999 X chromosome inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation. Tissue analysis showed that most somatic tissues (heart, lung, kidney, brain, liver) preferentially express wild-type Piga, suggesting these tissues require GPI-linked proteins, whereas spleen, thymus, and red blood cells had roughly equal proportions of Piga(+) and Piga(-) cells. Cre/loxP conditional knockout (EIIa-Cre), tissue fractionation, flow cytometry, X-inactivation analysis Proceedings of the National Academy of Sciences High 10377440
2001 GATA1-Cre-mediated Piga inactivation restricted to the erythroid/megakaryocytic lineage produced mice with up to 100% GPI-deficient red cells; the loss of GPI-linked proteins occurred late in erythroid differentiation, resulting in residual low-level GPI expression resembling PNH type II cells, which showed intermediate complement sensitivity. Recombination was also detected in megakaryocytes, mast cells, and eosinophils but not in neutrophils, lymphocytes, or non-hematopoietic tissues. GATA1-Cre/loxP conditional knockout, flow cytometry, complement sensitivity assay Blood High 11568013
2002 PIG-A mutant leukemic cells lacking GPI-anchored proteins showed decreased susceptibility to natural killer (NK) cell killing compared to PIG-A-rescued controls; killing was perforin-dependent (abolished by concanamycin A and calcium chelation); MHC class I expression and perforin sensitivity were equivalent, indicating the survival advantage is due to absence of a GPI-anchored NK-activating ligand(s). 51Cr-release NK cytotoxicity assay, PIG-A cDNA transfection rescue, pharmacological inhibition of perforin pathway, flow cytometry Blood Medium 12130519
2005 PIGA mutant K562 cells lacking GPI-anchored proteins survive NK cell cytotoxicity due to deficiency of stress-inducible GPI-linked ULBP1 and ULBP2; antibodies to ULBPs or to NKG2D (the ULBP receptor on NK cells) made GPI-expressing cells as resistant as GPI-deficient cells, directly linking ULBP absence to the survival advantage. NK cytotoxicity assay, antibody blocking experiments, flow cytometry for ULBP expression Blood Medium 16195329
2008 PIG-A-deficient human embryonic stem cells (due to absent PIG-A expression) could form embryoid bodies and differentiate into the three germ layers but failed to form trophoblasts; the trophoblast differentiation defect was due to absence of GPI-anchored BMP co-receptors, impairing full BMP4 signaling activation. PIG-A-null hES cell clones, BMP4 differentiation assay, BMP signaling assays, flow cytometry Cell Stem Cell Medium 18397754
2012 A germline nonsense mutation in PIGA (p.Arg412*) results in partial (not absent) GPI-anchor biosynthesis; transfection of the mutant construct into PIGA-null cells showed partial restoration of GPI-anchored protein surface expression, establishing that this hypomorphic allele retains residual function. Transfection complementation assay in PIGA-null cells, flow cytometry for GPI-anchored protein surface expression American Journal of Human Genetics Medium 22305531
2014 Four distinct PIGA mutations causing early-onset epileptic encephalopathy showed variable loss of PIGA enzymatic activity; transient expression of PIGA mutants in PIGA-deficient JY5 cells only partially or barely restored GPI-anchored protein surface expression, and the degree of activity loss correlated with clinical severity. Transfection complementation assay in PIGA-null JY5 cells, flow cytometry for GPI-anchored protein expression on blood granulocytes and transfected cells Neurology Medium 24706016
2014 An early frameshift mutation in PIGA (c.76dupT; p.Y26Lfs*3) produces a truncated hypomorphic protein via translation initiation at the second methionine (position 37); complementation assays confirmed that the shorter PIGA cDNA partially rescues CD59 surface expression in PIGA-null cells. Complementation assay in PIGA-null cell line, CD59 flow cytometry, molecular analysis of alternative translation initiation Human Mutation Medium 24357517
2017 A hypomorphic PIGA mutation (c.1234C>T) impairs neuronal differentiation in human iPSC-derived neural progenitors, with decreased proliferation, aberrant synapse formation, and abnormal membrane depolarization; neural progenitors also showed increased susceptibility to complement-mediated cytotoxicity, indicating defective complement regulation. Human iPSC model with PIGAc.1234C>T mutation, neural differentiation assays, electrophysiology, complement cytotoxicity assay PloS One Medium 28441409
1997 Restrictive GPI anchor synthesis in cwh6/gpi3 (yeast GPI3/PIG-A ortholog) mutant cells retards ER exit of cell wall protein precursors, causes ER proliferation, and results in secretion rather than cell wall incorporation of GPI-dependent cell wall proteins. Yeast conditional mutant analysis, subcellular fractionation, pulse-chase protein trafficking, ER morphology analysis Journal of Bacteriology Medium 9079905
1998 PIG-A mutations do not directly confer resistance to apoptosis: stable introduction of PIG-A cDNA into GPI-negative JY5 cells (restoring GPI-anchored protein surface expression) did not alter rates of apoptosis induced by Fas antibody, serum starvation, or gamma-irradiation, indicating that the PIG-A mutation and GPI-anchor absence are not the direct cause of apoptosis resistance in PNH. Stable transfection and retroviral transduction of PIG-A cDNA into GPI-null cells, apoptosis assays (Fas, serum starvation, irradiation) Blood Medium 9746796
2020 Jawsamycin selectively inhibits the fungal Spt14/Gpi3 (GPI3/PIG-A ortholog) catalytic subunit of the UDP-glycosyltransferase complex at the first step of GPI biosynthesis, with good selectivity over the human PIG-A functional homolog, demonstrating that the enzymatic activity of PIG-A/Spt14 is targetable by small molecules. Reporter gene-based screen in S. cerevisiae, antifungal activity assays, target identification via genetic interaction, in vivo mouse model Nature Communications Medium 32636417

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science (New York, N.Y.) 440 7680492
1994 Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. The EMBO journal 329 8306954
1994 Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria. The New England journal of medicine 212 8272086
2012 The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. American journal of human genetics 132 22305531
2014 The in vivo Pig-a assay: A report of the International Workshop On Genotoxicity Testing (IWGT) Workgroup. Mutation research. Genetic toxicology and environmental mutagenesis 131 25953398
1998 The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1. The EMBO journal 129 9463366
2008 In vivo mutation assay based on the endogenous Pig-a locus. Environmental and molecular mutagenesis 115 18288722
2005 PIG-A mutations in normal hematopoiesis. Blood 107 15687243
1997 Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion. The Journal of clinical investigation 103 9276719
1995 Temperature-sensitive yeast GPI anchoring mutants gpi2 and gpi3 are defective in the synthesis of N-acetylglucosaminyl phosphatidylinositol. Cloning of the GPI2 gene. The Journal of biological chemistry 102 7768896
2010 The in vivo Pig-a gene mutation assay, a potential tool for regulatory safety assessment. Environmental and molecular mutagenesis 97 20857433
1994 Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria. Blood 96 8167330
2014 PIGA mutations cause early-onset epileptic encephalopathies and distinctive features. Neurology 91 24706016
2011 Xenobiotic metabolizing cytochrome P450 in pig, a promising animal model. Current drug metabolism 87 21476973
1997 Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria. Proceedings of the National Academy of Sciences of the United States of America 85 9238050
2008 Erythrocyte-based Pig-a gene mutation assay: demonstration of cross-species potential. Mutation research 78 18790079
1999 Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene. Blood 76 10556176
2015 The genotypic and phenotypic spectrum of PIGA deficiency. Orphanet journal of rare diseases 75 25885527
2009 Pig-a mutation: kinetics in rat erythrocytes following exposure to five prototypical mutagens. Toxicological sciences : an official journal of the Society of Toxicology 75 19965957
1996 PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum. The Journal of biological chemistry 73 8900170
1995 Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type. Blood 72 8541557
1994 Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria. Blood 68 8193350
1995 Somatic mutations of the PIG-A gene found in Japanese patients with paroxysmal nocturnal hemoglobinuria. Blood 67 7531514
2013 A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload. American journal of medical genetics. Part A 63 24259288
1997 Restrictive glycosylphosphatidylinositol anchor synthesis in cwh6/gpi3 yeast cells causes aberrant biogenesis of cell wall proteins. Journal of bacteriology 63 9079905
1994 Mutations in the PIG-A gene causing partial deficiency of GPI-linked surface proteins (PNH II) in patients with paroxysmal nocturnal haemoglobinuria. British journal of haematology 60 7986731
2011 International Pig-a gene mutation assay trial: evaluation of transferability across 14 laboratories. Environmental and molecular mutagenesis 58 21910140
2006 Protein assembly line components in prodigiosin biosynthesis: characterization of PigA,G,H,I,J. Journal of the American Chemical Society 56 17002325
2005 Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP. Blood 56 16195329
1999 X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation. Proceedings of the National Academy of Sciences of the United States of America 53 10377440
2020 Lessons learned from 40 novel PIGA patients and a review of the literature. Epilepsia 52 32452540
2009 The use of PIG-A as a sentinel gene for the study of the somatic mutation rate and of mutagenic agents in vivo. Mutation research 48 20034593
1998 The PIG-A mutation and absence of glycosylphosphatidylinositol-linked proteins do not confer resistance to apoptosis in paroxysmal nocturnal hemoglobinuria. Blood 46 9746796
2013 Interlaboratory trial of the rat Pig-a mutation assay using an erythroid marker HIS49 antibody. Mutation research 45 23792374
2001 GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage and leads to circulating red cells with a partial deficiency in glycosyl phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II cells). Blood 44 11568013
2000 Impaired growth and elevated fas receptor expression in PIGA(+) stem cells in primary paroxysmal nocturnal hemoglobinuria. The Journal of clinical investigation 44 10974022
1995 Heterogeneous PIG-A mutations in different cell lineages in paroxysmal nocturnal hemoglobinuria. Blood 44 7888683
2002 Decreased susceptibility of leukemic cells with PIG-A mutation to natural killer cells in vitro. Blood 43 12130519
2011 Interlaboratory Pig-a gene mutation assay trial: Studies of 1,3-propane sultone with immunomagnetic enrichment of mutant erythrocytes. Environmental and molecular mutagenesis 41 22052433
2013 Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities. American journal of medical genetics. Part A 39 24259184
2001 Circulating PIG-A mutant T lymphocytes in healthy adults and patients with bone marrow failure syndromes. Experimental hematology 39 11750098
2011 Defining EMS and ENU dose-response relationships using the Pig-a mutation assay in rats. Mutation research 38 21729764
2008 Trophoblast differentiation defect in human embryonic stem cells lacking PIG-A and GPI-anchored cell-surface proteins. Cell stem cell 38 18397754
2006 The mutation rate in PIG-A is normal in patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood 38 16543465
1987 Vestibular nuclear complex in the guinea pig: a cytoarchitectonic study and map in three planes. The Journal of comparative neurology 38 3571524
2011 International Pig-a gene mutation assay trial (stage III): results with N-methyl-N-nitrosourea. Environmental and molecular mutagenesis 37 22167885
1999 CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia. British journal of haematology 37 10086790
2016 TSPO PIGA Ligands Promote Neurosteroidogenesis and Human Astrocyte Well-Being. International journal of molecular sciences 36 27367681
2015 A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2. American journal of medical genetics. Part A 36 26545172
2014 Human erythrocyte PIG-A assay: an easily monitored index of gene mutation requiring low volume blood samples. Environmental and molecular mutagenesis 35 25412990
2011 Report on stage III Pig-a mutation assays using N-ethyl-N-nitrosourea-comparison with other in vivo genotoxicity endpoints. Environmental and molecular mutagenesis 35 22167886
2014 The in vitro PIG-A gene mutation assay: mutagenicity testing via flow cytometry based on the glycosylphosphatidylinositol (GPI) status of TK6 cells. Archives of toxicology 34 25417052
2014 Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. Human mutation 33 24357517
2015 Confirmation of Pig-a mutation in flow cytometry-identified CD48-deficient T-lymphocytes from F344 rats. Mutagenesis 32 25820172
2020 Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol. Nature communications 31 32636417
2011 Report on stage III Pig-a mutation assays using benzo[a]pyrene. Environmental and molecular mutagenesis 31 22052432
1998 New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria. Blood 31 9787183
1995 A 6-Mb YAC contig in Xp22.1-p22.2 spanning the DXS69E, XE59, GLRA2, PIGA, GRPR, CALB3, and PHKA2 genes. Genomics 31 7759104
2006 PIG-A mutations in paroxysmal nocturnal hemoglobinuria and in normal hematopoiesis. Leukemia & lymphoma 30 16923549
1990 Epidermal cell kinetics of the pig: a review. Cell and tissue kinetics 29 2202514
2015 CD48-deficient T-lymphocytes from DMBA-treated rats have de novo mutations in the endogenous Pig-a gene. Environmental and molecular mutagenesis 25 26033714
2015 Both PIGA and PIGL mutations cause GPI-a deficient isolates in the Tk6 cell line. Environmental and molecular mutagenesis 23 25970100
1998 Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes. Genomics 23 9479493
2016 A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy. Brain & development 22 26923721
2013 Sensitivity of the Pig-a assay for detecting gene mutation in rats exposed acutely to strong clastogens. Mutagenesis 22 23677247
2020 Deciphering the premature mortality in PIGA-CDG - An untold story. Epilepsy research 21 33508693
2017 The Pig-a Gene Mutation Assay in Mice and Human Cells: A Review. Basic & clinical pharmacology & toxicology 21 28481423
2015 Mouse Pig-a and micronucleus assays respond to N-ethyl-N-nitrosourea, benzo[a]pyrene, and ethyl carbamate, but not pyrene or methyl carbamate. Environmental and molecular mutagenesis 21 26186091
2021 Recent advances of vitamin D in immune, reproduction, performance for pig: a review. Animal health research reviews 20 34075873
2015 Rat Pig-a mutation assay responds to the genotoxic carcinogen ethyl carbamate but not the non-genotoxic carcinogen methyl carbamate. Mutagenesis 20 25833916
2005 PIGA (N,N-Di-n-butyl-5-chloro-2-(4-chlorophenyl)indol-3-ylglyoxylamide), a new mitochondrial benzodiazepine-receptor ligand, induces apoptosis in C6 glioma cells. Chembiochem : a European journal of chemical biology 20 15883977
2019 Pig-a gene mutation database. Environmental and molecular mutagenesis 18 31090953
2016 The in vitro PIG-A gene mutation assay: glycosylphosphatidylinositol (GPI)-related genotype-to-phenotype relationship in TK6 cells. Archives of toxicology 17 27100116
2015 Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane. Mutagenesis 17 25934985
2020 PIG-A gene mutation as a genotoxicity biomarker in human population studies: An investigation in lead-exposed workers. Environmental and molecular mutagenesis 16 32285465
2017 Development of an in vitro PIG-A gene mutation assay in human cells. Mutagenesis 16 28057708
2017 A hypomorphic PIGA gene mutation causes severe defects in neuron development and susceptibility to complement-mediated toxicity in a human iPSC model. PloS one 16 28441409
1999 Genetic instability and the etiology of somatic PIG-A mutations in paroxysmal nocturnal hemoglobinuria. Blood cells, molecules & diseases 16 10389589
2024 Maternal recognition of pregnancy in the pig: A servomechanism involving sex steroids, cytokines and prostaglandins. Animal reproduction science 15 38522133
2020 Human blood PIG-A mutation and micronucleated reticulocyte flow cytometric assays: Method optimization and evaluation of intra- and inter-subject variation. Environmental and molecular mutagenesis 15 32572998
2017 Spectrum of Pig-a mutations in T lymphocytes of rats treated with procarbazine. Mutagenesis 15 29237063
2016 A population study using the human erythrocyte PIG-A assay. Environmental and molecular mutagenesis 15 27581231
2015 Comparison of male versus female responses in the Pig-a mutation assay. Mutagenesis 15 25833915
2013 Assessment of the genotoxic potential of azidothymidine in the comet, micronucleus, and Pig-a assay. Toxicological sciences : an official journal of the Society of Toxicology 15 23811826
2018 A novel PIGA mutation in a Taiwanese family with early-onset epileptic encephalopathy. Seizure 14 29656098
2012 Simple monitoring of gene targeting efficiency in human somatic cell lines using the PIGA gene. PloS one 14 23056640
1995 The PIG-A gene somatic mutation responsible for paroxysmal nocturnal hemoglobinuria. Haematologica 14 8647522
2021 How Does Protein Nutrition Affect the Epigenetic Changes in Pig? A Review. Animals : an open access journal from MDPI 13 33669864
2018 A likely pathogenic variant putatively affecting splicing of PIGA identified in a multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2) family pedigree via whole-exome sequencing. Molecular genetics & genomic medicine 12 29974678
2013 Detection of in vivo mutation in the Hprt and Pig-a genes of rat lymphocytes. Methods in molecular biology (Clifton, N.J.) 12 23896872
2002 The effect of GPI-anchor deficiency on apoptosis in mice carrying a Piga gene mutation in hematopoietic cells. Journal of leukocyte biology 12 12488505
2018 A novel germline PIGA mutation causes early-onset epileptic encephalopathies in Chinese monozygotic twins. Brain & development 11 29502866
2017 Dose-response relationship of temozolomide, determined by the Pig-a, comet, and micronucleus assay. Archives of toxicology 11 28197649
2017 Establishing a novel Pig-a gene mutation assay in L5178YTk+/- mouse lymphoma cells. Environmental and molecular mutagenesis 11 29098723
2003 Intracellular accumulation of pIgA-R and regulators of transcytotic trafficking in cholestatic rat hepatocytes. Hepatology (Baltimore, Md.) 11 14578858
1997 PIG-A gene mutations in four Taiwanese patients with paroxysmal nocturnal haemoglobinuria following aplastic anaemia. British journal of haematology 11 9163589
2022 A Pig-a conditional knock-out mice model mediated by Vav-iCre: stable GPI-deficient and mild hemolysis. Experimental hematology & oncology 10 35033195
2021 Classical, Molecular, and Genomic Cytogenetics of the Pig, a Clinical Perspective. Animals : an open access journal from MDPI 10 33925534
2021 Rab11-FIP1 and Rab11-FIP5 Regulate pIgR/pIgA Transcytosis through TRIM21-Mediated Polyubiquitination. International journal of molecular sciences 10 34638806
2016 In Vivo Pig-a gene mutation assay: Guidance for 3Rs-friendly implementation. Environmental and molecular mutagenesis 10 27770464

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