RAG2

Chr 11

recombination activating 2

Also known as: RAG-2

NCBI Gene: 5897 ENSG00000175097 UniProt: P55895

The RAG2 protein forms a complex with RAG1 that mediates DNA cleavage during V(D)J recombination, the process that assembles diverse immunoglobulin and T-cell receptor genes in developing B and T lymphocytes. Mutations cause autosomal recessive severe combined immunodeficiency including Omenn syndrome, characterized by absent B cells and severe immune dysfunction often presenting in infancy. RAG2 acts as a chromatin sensor that recruits the RAG complex to specific histone modifications and is essential for generating functional adaptive immune responses.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCombined cellular and humoral immune defects with granulomas

UniProtSevere combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive

UniProtOmenn syndrome

Clinical highlights

Gene-disease validity (ClinGen)

recombinase activating gene 2 deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.79

LOEUF

LOF

Mechanism· G2P

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