ArticleThe Journal of allergy and clinical immunology2023
A gain-of-function variation in PLCG1 causes a new immune dysregulation disease.
Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Proteomic Mendelian randomization and machine learning reveal causal plasma biomarkers in cardiorenal comorbidity.Renal failure · 2026Article
- Optogenetic control of PLC-γ1 activity directs cell motility.The Journal of cell biology · 2026Article
- Potential link between Gordonibacter pamelaeae and phospholipase C gamma 1 in osteoarthritis.AMB Express · 2026Article
- Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.Molecular genetics and genomics : MGG · 2026Article
- PrPStem cell reports · 2026Article
- Integrated analysis of single-cell RNA sequencing, transcriptomics, and thermal proteome profiling identifies PLCG1 as the therapeutic target of isopimpinellin in treating rheumatoid arthritis.Cellular & molecular biology letters · 2026Article
- Integrated analysis of differential m6A methylation and transcriptome profiles in ovaries of young and aged Qira black sheep.BMC genomics · 2026Article
- D-glucose uptake inhibits bovine alphaherpesvirus 1 post-binding cell process entry via inhibition of PLC-γ1 signaling in a glucose transporter 1-independent manner.Microbiology spectrum · 2026Article
- Genetic admixture and adaptive signatures of Guanling cattle revealed by whole-genome sequence.BMC genomics · 2026Article
- Quantifying pathway perturbations based on gene network rewiring in sepsis progression toward death or survival.Frontiers in bioinformatics · 2026Article
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Early-onset systemic lupus erythematosus in a patient with an inborn error of immunity caused by a NRAS mutation and treated with telitacicept.Molecular and cellular pediatrics · 2025Article
- A novel inositol phosphate metabolism signature predicts survival prognosis in low grade glioma.Discover oncology · 2025Article
- Inflammation related proteins and PLCG1 may contribute to papillary thyroid carcinoma risk through a potential regulatory axis.Discover oncology · 2025Article
- Optogenetic control of PLC-γ1 activity polarizes cell motility.bioRxiv : the preprint server for biology · 2025Article
- Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.medRxiv : the preprint server for health sciences · 2025Article
- Hyperactive PLCG1 induces cell-autonomous and bystander T cell activation and drug resistance.EMBO reports · 2025Article
- Heterozygous variants ineLife · 2025Article
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HTActa neuropsychiatrica · 2025Review
- Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundPhospholipase C (PLC) γ1 is a critical enzyme regulating nuclear factor-κB (NF-κB), extracellular signal-related kinase, mitogen-activated protein kinase, and nuclear factor of activated T cells signaling pathways, yet germline PLCG1 mutation in human disease has not been reported.
objectiveWe aimed to investigate the molecular pathogenesis of a PLCG1 activating variant in a patient with immune dysregulation.
methodsWhole exome sequencing was used to identify the patient's pathogenic variants. Bulk RNA sequencing, single-cell RNA sequencing, quantitative PCR, cytometry by time of flight, immunoblotting, flow cytometry, luciferase assay, IP-One ELISA, calcium flux assay, and cytokine measurements in patient PBMCs and T cells and COS-7 and Jurkat cell lines were used to define inflammatory signatures and assess the impact of the PLCG1 variant on protein function and immune signaling.
resultsWe identified a novel and de novo heterozygous PLCG1 variant, p.S1021F, in a patient presenting with early-onset immune dysregulation disease. We demonstrated that the S1021F variant is a gain-of-function variant, leading to increased inositol-1,4,5-trisphosphate production, intracellular Ca
conclusionsOur study highlights the critical role of PLCγ1 in maintaining immune homeostasis. We illustrate immune dysregulation as a consequence of PLCγ1 activation and provide insight into therapeutic targeting of PLCγ1.
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Registered trials
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.