RAG1

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Protein-coding gene in the species Homo sapiens

title: "RAG1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/RAG1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the RAG1 gene.

The RAG1 and RAG2 genes are largely conserved in humans. 55.99% and 55.98% of the encoded amino acids contain no reported variants, respectively.

Function

The protein encoded by this gene is involved in antibody and T-cell receptor V(D)J recombination. RAG-1 is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG-2. The RAG-1/2 complex recognizes recombination signal sequences (RSSs) that flank the V, D and J regions in the genes that encode the heavy and light chains of antibodies and components of T-cell receptors. The complex binds to the RSSs and nicks the DNA. This leads to the removal of the intervening DNA and the eventual ligation of the V, D and J sequences. Defects in this gene can cause several different diseases.

Clinical significance

Because of these effects, Rag1 deletion is used in mouse models of disease to impair T cell and B cell development, and functionally deletes mature T and B cells from the immune system.

In humans, RAG deficiency was first recognised as a form of immune dysregulation known as Omenn syndrome. RAG deficiency is considered an autosomal recessive disease. The disorder is generally identified in infants. Complete loss-of-function in RAG1/2, the main components responsible for V(D)J recombination activity, produces severe immunodeficiency in humans. Hypomorphic RAG variants can retain partial recombination activity and result in a distinct phenotype of combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A), as well as other milder forms, such as antibody deficiency, Idiopathic CD4+ T lymphopenia or vasculitis. RAG deficiency can be measured by in vitro quantification of recombination activity. 71 RAG1 and 39 RAG2 variants have been functionally assayed to date (2019) (less than 10% of the potential point mutations that may cause disease). However, top candidate variants have been ranked by their predicted clinical relevance.

Use in phylogenetics

RAG1 is frequently used as a marker in phylogenetic studies. That is, RAG1 sequences are often used to construct phylogenetic trees in order to investigate the relationships between species or higher taxa. Although the selection of RAG1 was somewhat arbitrary, it is one of several universal nuclear protein-coding loci (NPCL) that are applicable across diverse taxa and show good phylogenetic discrimination. For instance, RAG1 has been successfully used to make phylogenetic inferences within all major groups of fish and reptiles. In many cases, RAG1 is used together with mitochondrial sequences as these evolve much faster and thus provide information about more closely related taxa. A combination of nuclear and mitochondrial DNA is usually recommended due to fact that they may yield discrepant phylogenetic relationships, a phenomenon called mito-nuclear discordance.

References

References

  1. "Entrez Gene: Recombination activating gene 1".
  2. (2013). "Kuby Immunology". W. H. Freeman and Company.
  3. "B6.129S7-Rag1tm1Mom/J Mouse Strain Details".
  4. (May 1998). "Partial V(D)J recombination activity leads to Omenn syndrome". Cell.
  5. (May 2008). "An immunodeficiency disease with RAG mutations and granulomas". The New England Journal of Medicine.
  6. (November 2015). "Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency". The Journal of Clinical Investigation.
  7. (August 2014). "Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States". JAMA.
  8. (2015-07-17). "Leaky RAG Deficiency in Adult Patients with Impaired Antibody Production against Bacterial Polysaccharide Antigens". PLOS ONE.
  9. (June 2011). "Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations". Blood.
  10. (2020-10-21). "Vasculitis as a Major Morbidity Factor in Patients With Partial RAG Deficiency". Frontiers in Immunology.
  11. (June 2018). "Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency". The Journal of Allergy and Clinical Immunology.
  12. (April 2014). "A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency". The Journal of Allergy and Clinical Immunology.
  13. (February 2019). "Recombination activity of human recombination-activating gene 2 (RAG2) mutations and correlation with clinical phenotype". The Journal of Allergy and Clinical Immunology.
  14. (October 2019). "Predicting the Occurrence of Variants in RAG1 and RAG2". Journal of Clinical Immunology.
  15. (2009-09-01). "Length variation in the N-terminal domain of the recombination-activating gene 1 (RAG1) across squamates". Molecular Phylogenetics and Evolution.
  16. (2012-06-14). "The Development of Three Long Universal Nuclear Protein-Coding Locus Markers and Their Application to Osteichthyan Phylogenetics with Nested PCR". PLOS ONE.
  17. (2024-02-08). "Systematic revision of the Eyelash Palm-Pitviper Bothriechis schlegelii (Serpentes, Viperidae), with the description of five new species and revalidation of three". Evolutionary Systematics.
  18. (2019-03-26). "Taxonomic and conservation implications of population genetic admixture, mito-nuclear discordance, and male-biased dispersal of a large endangered snake, Drymarchon couperi". PLOS ONE.

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