RAG1
Identifiers
Aliases	RAG1, RAG-1, RNF74, recombination activating gene 1, recombination activating 1
External IDs	OMIM: 179615 MGI: 97848 HomoloGene: 387 GeneCards: RAG1
Gene location ( Human) Chr. Chromosome 11 (human) [1] Band 11p12 Start 36,510,709 bp [1] End 36,593,156 bp [1]
Gene location ( Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 E2|2 53.88 cM Start 101,468,627 bp [2] End 101,479,846 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in thymus bone marrow spleen stromal cell of endometrium bone marrow cells islet of Langerhans left adrenal gland thyroid gland left lobe of thyroid gland right lobe of thyroid gland Top expressed in thymus bone marrow body of femur sternocleidomastoid muscle inner cell mass sexually immature organism trachea lens cochlea spermatid More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding sequence-specific DNA binding protein homodimerization activity ubiquitin protein ligase activity histone binding zinc ion binding metal ion binding ubiquitin-protein transferase activity protein binding catalytic activity nuclease activity endonuclease activity hydrolase activity transferase activity identical protein binding double-stranded DNA endodeoxyribonuclease activity Cellular component nucleoplasm nucleus DNA recombinase complex endodeoxyribonuclease complex Biological process positive regulation of T cell differentiation histone monoubiquitination DNA recombination negative regulation of cysteine-type endopeptidase activity involved in apoptotic process adaptive immune response T cell differentiation in thymus nucleic acid phosphodiester bond hydrolysis thymus development negative regulation of thymocyte apoptotic process T cell homeostasis negative regulation of T cell apoptotic process immune response V(D)J recombination pre-B cell allelic exclusion B cell differentiation metabolism regulation of T cell differentiation protein autoubiquitination visual learning regulation of behavioral fear response chromatin organization Sources: Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5896 19373 Ensembl ENSG00000166349 ENSMUSG00000061311 UniProt P15918 P15919 RefSeq (mRNA) NM_000448 NM_009019 RefSeq (protein) NP_000439 NP_001364206 NP_001364207 NP_001364208 NP_001364209 NP_033045 Location (UCSC) Chr 11: 36.51 – 36.59 Mb Chr 2: 101.47 – 101.48 Mb PubMed search [3] [4]
Wikidata
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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]

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. ^[7] Defects in this gene can cause several different diseases. ^[5]

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. ^[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]

References

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