PIGL Gene

HGNC Family	Phosphatidylinositol glycan anchor biosynthesis (PIG)
Name	phosphatidylinositol glycan anchor biosynthesis, class L
Description	This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPIGL encodes a de‐N‐acetylase that is essential for the early steps of glycosylphosphatidylinositol (GPI) anchor biosynthesis, a process critical for attaching a wide array of proteins to the cell membrane. Disruption of PIGL function, as demonstrated in patients with CHIME syndrome, leads to reduced surface expression of GPI‐anchored proteins, which in turn manifests clinically as colobomas, congenital heart defects, ichthyosiform dermatosis, intellectual disability, and ear anomalies. Exome analyses further implicate pathogenic variants in PIGL among individuals with neurodevelopmental disorders, underscoring its central role in the GPI‐anchor biogenesis pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its involvement in CHIME syndrome, mutations in PIGL may lead to other phenotypes such as hyperphosphatasia with mental retardation syndrome (HPMRS). Frameshift mutations that cause premature truncation in PIGL result in a partial impairment of GPI‐anchored protein expression, clinically correlating with elevated serum alkaline phosphatase, severe developmental delay, and distinctive dysmorphic features. Moreover, the discovery of intragenic deletions mediated by repetitive Alu elements highlights a broader mutational spectrum that predisposes to disease‐causing copy‐number variations within PIGL."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in GPI-anchor biosynthesis, recent investigations have uncovered a novel nuclear function for PIGL in modulating the tumor microenvironment in hepatocellular carcinoma. Specifically, nuclear PIGL interferes with the cMyc/BRD4 complex on remote promoters, leading to decreased expression of chemokines such as CCL2 and CCL20, which in turn limits the recruitment of immunosuppressive cells like macrophages and regulatory T cells. This phosphorylation-regulated subcellular localization, mediated by FGFR2-dependent modification at Y81, not only impacts tumor cell survival but also serves as a potential biomarker to optimize combination therapies using lenvatinib and programmed death-1 blockade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bobby G Ng, Karl Hackmann, Melanie A Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the glycosylphosphatidylinositol gene PIGL cause CHIME syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.02.010"}], "href": "https://doi.org/10.1016/j.ajhg.2012.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22444671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22444671"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alistair T Pagnamenta, Yoshiko Murakami, John M Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2017.32"}], "href": "https://doi.org/10.1038/ejhg.2017.32"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28327575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28327575"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ikuma Fujiwara, Yoshiko Murakami, Tetsuya Niihori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in PIGL in a patient with Mabry syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.36987"}], "href": "https://doi.org/10.1002/ajmg.a.36987"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25706356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25706356"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Amy Knight Johnson, Gerald Bradley Schaefer, Jennifer Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alu-mediated deletion of PIGL in a Patient with CHIME syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38181"}], "href": "https://doi.org/10.1002/ajmg.a.38181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28371479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28371479"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hua Yu, Tiezhu Shi, Linli Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated nuclear PIGL disrupts the cMyc/BRD4 axis and improves PD-1 blockade therapy by dampening tumor immune evasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Immunol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41423-023-01048-3"}], "href": "https://doi.org/10.1038/s41423-023-01048-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37280393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37280393"}]}]}]}
Synonyms	CHIME
Proteins	PIGL_HUMAN
NCBI Gene ID	9487
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PIGL has 7,495 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for PIGL from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PIGL Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PIGL gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PIGL gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PIGL gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PIGL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PIGL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PIGL gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PIGL gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PIGL gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PIGL gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PIGL gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PIGL gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PIGL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PIGL gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PIGL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PIGL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PIGL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PIGL gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PIGL gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PIGL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PIGL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PIGL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PIGL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PIGL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PIGL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PIGL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PIGL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PIGL gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PIGL gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PIGL protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PIGL gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving PIGL gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PIGL gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PIGL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PIGL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PIGL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PIGL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PIGL gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PIGL gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PIGL gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PIGL from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.