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Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the RAG1 gene.[5]
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.[6]
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.[7] Defects in this gene can cause several different diseases.[5]
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.[8]
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[9] and result in a distinct phenotype of combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A),[10][11][12] as well as other milder forms, such as antibody deficiency,[13] Idiopathic CD4+ T lymphopenia [14] or vasculitis.[15] RAG deficiency can be measured by in vitro quantification of recombination activity.[16][17][18] 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.[6]
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