RAG2
Chr 11ARrecombination activating 2
Also known as: RAG-2
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.
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
500 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 | 19 | 9 | 20 | 0 | 48 |
Likely Pathogenic | 15 | 42 | 14 | 0 | 71 |
VUS | 2 | 180 | 9 | 5 | 196 |
Likely Benign | 0 | 4 | 2 | 156 | 162 |
Benign | 0 | 1 | 3 | 0 | 4 |
Conflicting | — | 17 | |||
| Total | 36 | 236 | 48 | 161 | 498 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAG2 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools