RAG1 Gene: Recombination Activating Gene 1
Essential for V(D)J recombination, immune diversity, and associated with immunodeficiency and autoimmune disorders.
Gene Information Card
| Symbol | RAG1 |
|---|---|
| Full Name | Recombination Activating Gene 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p12 |
| NCBI Gene ID | 5896 ncbi.nlm.nih.gov/gene/5896 |
| Ensembl ID | ENSG00000166313 |
| UniProt ID | P15918 |
| OMIM ID | 179615 |
| HGNC ID | 9831 |
| Aliases | RAG-1, RNF74, MGC43321 |
Description
The RAG1 gene encodes the recombination activating protein 1, a key component of the V(D)J recombination machinery. This process is essential for the generation of diverse immunoglobulin and T-cell receptor genes, enabling adaptive immunity. RAG1, together with RAG2, introduces DNA double-strand breaks at recombination signal sequences, initiating the assembly of antigen receptor genes. Mutations in RAG1 lead to severe combined immunodeficiency (SCID) and related disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe combined immunodeficiency (SCID) (autosomal recessive T-cell negative, B-cell negative, NK-cell positive) | Loss-of-function mutations in RAG1 impair V(D)J recombination, leading to failure of T and B cell development. | ClinVar, OMIM |
| Omenn syndrome | Hypomorphic mutations in RAG1 result in partial V(D)J recombination activity, causing oligoclonal T cells and autoimmune manifestations. | OMIM, ClinVar |
| Combined immunodeficiency with granulomatous disease | RAG1 mutations can lead to atypical presentations with granulomatous inflammation and autoimmunity. | ClinVar, OMIM |
| Autoimmune diseases (e.g., autoimmune cytopenias, alopecia, myasthenia gravis) | RAG1 mutations may cause immune dysregulation, leading to autoimmunity in some patients. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymphoid tissues (thymus, spleen, lymph nodes) | Not available (nTPM not provided in GTEx) | High expression in developing lymphocytes; not measured in standard tissue panels. |
| Bone marrow | Not available | Expression in hematopoietic progenitors; essential for B cell development. |
| Peripheral blood | Not available | Expression in mature lymphocytes is low but present. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Ramos (Burkitt lymphoma) | Not available | B cell line expressing RAG1; used in V(D)J recombination studies. |
| Nalm6 (B cell precursor leukemia) | Not available | Pre-B cell line with active RAG1 expression. |
| Jurkat (T cell leukemia) | Not available | T cell line; RAG1 expression is low but can be induced. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.256_257delAA (p.Lys86ValfsTer33) | Frameshift | Rare | Loss of function; causes SCID. |
| c.368-2A>G (splice site) | Splice site | Rare | Loss of function; causes SCID. |
| c.2179C>T (p.Arg727Ter) | Nonsense | Rare | Loss of function; causes SCID. |
| c.256C>T (p.Arg86Trp) | Missense | Rare | Hypomorphic; associated with Omenn syndrome. |
| c.368G>A (p.Arg123His) | Missense | Rare | Hypomorphic; associated with combined immunodeficiency. |
Mutation functional classification
Loss of Function (LOF)
Complete loss of RAG1 function abolishes V(D)J recombination, leading to T-B-NK+ SCID.
Gain of Function (GOF)
No gain-of-function mutations have been reported; RAG1 activity is tightly regulated.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with RAG1/RAG2 complex formation, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • zinc ion binding |
| • endonuclease activity | • DNA recombination |
| • V(D)J recombination | • immune system process |
Pathways
• V(D)J recombination (Reactome: R-HSA-5690714)
• Immune system (Reactome: R-HSA-168256)
• Hematopoietic cell lineage (KEGG: hsa04640)
Protein Summary
The RAG1 protein (UniProt P15918) is a 1043-amino acid protein with multiple domains: a zinc-binding RING finger, a core domain, and a C-terminal region. It forms a complex with RAG2 to recognize recombination signal sequences and introduce DNA double-strand breaks. The protein is essential for lymphocyte development and adaptive immunity. Mutations affecting its catalytic activity or DNA binding lead to immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAG1 Knockout HEK293 Cell Line | EDJ-KQ1546 | Human | 5896 | Details Get a Quote |
| IRAG1 Knockout HEK293 Cell Line | EDJ-KQ1850 | Human | 10335 | Details Get a Quote |
| PRAG1 Knockout HEK293 Cell Line | EDJ-KQ14868 | Human | 157285 | Details Get a Quote |
| IRAG1 Knockout HCT 116 Cell Line | EDJ-KQ21714 | Human | 10335 | Details Get a Quote |
| PRAG1 Knockout A-549 Cell Line | EDJ-KQ45326 | Human | 157285 | Details Get a Quote |
| PRAG1 Knockout HCT 116 Cell Line | EDJ-KQ45327 | Human | 157285 | Details Get a Quote |
| PRAG1 Knockout HeLa Cell Line | EDJ-KQ45328 | Human | 157285 | Details Get a Quote |
| RAG1 Knockout HeLa Cell Line | EDJ-KQ54289 | Human | 5896 | Details Get a Quote |
| IRAG1 Knockout HeLa Cell Line | EDJ-KQ55384 | Human | 10335 | Details Get a Quote |
| RAG1 Knockout A-549 Cell Line | EDJ-KQ62785 | Human | 5896 | Details Get a Quote |
| IRAG1 Knockout A-549 Cell Line | EDJ-KQ63865 | Human | 10335 | Details Get a Quote |
| RAG1 Knockout HCT 116 Cell Line | EDJ-KQ71250 | Human | 5896 | Details Get a Quote |
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