RAG1
Chr 11ARrecombination activating 1
Also known as: RAG-1, RNF74
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.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
497 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 27 | 6 | 18 | 0 | 51 |
Likely Pathogenic | 22 | 12 | 12 | 0 | 46 |
VUS | 0 | 133 | 23 | 1 | 157 |
Likely Benign | 0 | 7 | 1 | 209 | 217 |
Benign | 0 | 3 | 8 | 0 | 11 |
Conflicting | — | 11 | |||
| Total | 49 | 161 | 62 | 210 | 493 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAG1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools