RAG1

Chr 11AR

recombination activating 1

Also known as: RAG-1, RNF74

NCBI Gene: 5896 ENSG00000166349 UniProt: P15918 OMIM: 179615

RAG1 encodes the catalytic component of the RAG complex 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. Autosomal recessive mutations cause severe combined immunodeficiency with absent B cells, Omenn syndrome, combined immune defects with granulomas, and T-cell lymphopenia with autoimmunity, affecting both cellular and humoral immunity. The gene is highly intolerant to loss-of-function variants (pLI near 1.0), reflecting its essential role in adaptive immune system development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunityMIM #609889

Combined cellular and humoral immune defects with granulomasMIM #233650

Omenn syndromeMIM #603554

Severe combined immunodeficiency, B cell-negativeMIM #601457

Clinical highlights

Gene-disease validity (ClinGen)

recombinase activating gene 1 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

185

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

📖