ArticleThe Journal of clinical investigation2010
Analysis of mutations from SCID and Omenn syndrome patients reveals the central role of the Rag2 PHD domain in regulating V(D)J recombination.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- An antagonistically pleiotropic gene regulates vertebrate growth, maturity, and lifespan.Nature communications · 2026Article
- Inborn Errors of Immunity and Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- The DNA binding domain and the C-terminal region of DNA Ligase IV specify its role in V(D)J recombination.PloS one · 2023Article
- Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus.Viruses · 2022Article
- Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients.Journal of clinical immunology · 2022Article
- Binding and allosteric transmission of histone H3 Lys-4 trimethylation to the recombinase RAG-1 are separable functions of the RAG-2 plant homeodomain finger.The Journal of biological chemistry · 2020Article
- Recombination activity of human recombination-activating gene 2 (RAG2) mutations and correlation with clinical phenotype.The Journal of allergy and clinical immunology · 2019Article
- RAG gene defects at the verge of immunodeficiency and immune dysregulation.Immunological reviews · 2019Review
- RAG Deficiency: Two Genes, Many Diseases.Journal of clinical immunology · 2018Review
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
- Human RAG mutations: biochemistry and clinical implications.Nature reviews. Immunology · 2016Review
- Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome.Immunologic research · 2016Article
- DNA Ligase IV regulates XRCC4 nuclear localization.DNA repair · 2014Article
- Optimized cell transplantation using adult rag2 mutant zebrafish.Nature methods · 2014Article
- A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency.The Journal of allergy and clinical immunology · 2014Article
- RAG2's acidic hinge restricts repair-pathway choice and promotes genomic stability.Cell reports · 2013Article
- Reciprocal regulation of Rag expression in thymocytes by the zinc-finger proteins, Zfp608 and Zfp609.Genes and immunity · 2013Article
- Role of non-homologous end joining in V(D)J recombination.Immunologic research · 2012Review
- A novel homozygous mutation in recombination activating gene 2 in 2 relatives with different clinical phenotypes: Omenn syndrome and hyper-IgM syndrome.The Journal of allergy and clinical immunology · 2012Article
- Roles for histone H3K4 methyltransferase activities during immunoglobulin class-switch recombination.Biochimica et biophysica acta · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Rag2 plays an essential role in the generation of antigen receptors. Mutations that impair Rag2 function can lead to severe combined immunodeficiency (SCID), a condition characterized by complete absence of T and B cells, or Omenn syndrome (OS), a form of SCID characterized by the virtual absence of B cells and the presence of oligoclonal autoreactive T cells. Here, we present a comparative study of a panel of mutations that were identified in the noncanonical plant homeodomain (PHD) of Rag2 in patients with SCID or OS. We show that PHD mutant mouse Rag2 proteins that correspond to those found in these patients greatly impaired endogenous recombination of Ig gene segments in a Rag2-deficient pro-B cell line and that this correlated with decreased protein stability, impaired nuclear localization, and/or loss of the interaction between Rag2 and core histones. Our results demonstrate that point mutations in the PHD of Rag2 compromise the functionality of the entire protein, thus explaining why the phenotype of cells expressing PHD point mutants differs from those expressing core Rag2 protein that lacks the entire C-terminal region and is therefore devoid of the regulation imposed by the PHD. Together, our findings reveal the various deleterious effects of PHD Rag2 mutations and demonstrate the crucial role of this domain in regulating antigen receptor gene assembly. We believe these results reveal new mechanisms of immunodeficiency in SCID and OS.
Indexed as
Identifiers
What OpenQuestion holds
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.