Recombinase activating gene 1 deficiency: genes and variants
Recombinase activating gene 1 deficiency is linked to 1 analyzed protein (RAG1). 8 DNA variants are known to cause it; 17 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Recombinase activating gene 1 deficiency
RAG1: V(D)J recombination-activating protein 1
It initiates V(D)J recombination by cutting antigen-receptor gene segments, creating the enormous receptor diversity required for adaptive immunity. Biallelic severe loss-of-function variants cause severe combined immunodeficiency, while hypomorphic alleles can cause Omenn syndrome or combined immunodeficiency with autoimmunity.
8 disease-causing and 17 uncertain variants in RAG1 are linked to Recombinase activating gene 1 deficiency.
Where Recombinase activating gene 1 deficiency variants cluster
- RAG1 NBD (positions 392–459): 5 of 8 disease-causing changes, 9.6× more than its size predicts.
Known disease-causing variants in Recombinase activating gene 1 deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| RAG1 R394W | 394 | NBD | Disease-causing (★★★) |
| RAG1 R394Q | 394 | NBD | Disease-causing (★★★) |
| RAG1 R396H | 396 | NBD | Disease-causing (★★★) |
| RAG1 R716Q | 716 | Disease-causing (★★★) | |
| RAG1 R561C | 561 | Disease-causing (★★★) | |
| RAG1 R699W | 699 | Disease-causing (★★★) | |
| RAG1 R404Q | 404 | NBD | Disease-causing (★★★) |
| RAG1 A444V | 444 | NBD | Disease-causing (★★★) |
Which prediction tools work for Recombinase activating gene 1 deficiency
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 97 out of 100
- CADD: 96 out of 100
- phyloP: 85 out of 100
- PolyPhen-2: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive is also caused by RAG1 variants; they fall mostly in different places as the Recombinase activating gene 1 deficiency variants (52 disease-causing).
- Combined immunodeficiency with skin granulomas is also caused by RAG1 variants; they fall mostly in different places as the Recombinase activating gene 1 deficiency variants (49 disease-causing).
- Combined immunodeficiency due to partial RAG1 deficiency is also caused by RAG1 variants; they fall mostly in different places as the Recombinase activating gene 1 deficiency variants (13 disease-causing).
- Histiocytic medullary reticulosis is also caused by RAG1 variants; they fall mostly in different places as the Recombinase activating gene 1 deficiency variants (11 disease-causing).
- Severe combined immunodeficiency disease is also caused by RAG1 variants; they fall mostly in different places as the Recombinase activating gene 1 deficiency variants (8 disease-causing).
Diseases related to Recombinase activating gene 1 deficiency
- Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, also linked to RAG1
- Combined immunodeficiency with skin granulomas, also linked to RAG1
- Severe combined immunodeficiency disease, also linked to RAG1
- Histiocytic medullary reticulosis, also linked to RAG1
- Inherited Immunodeficiency Diseases, also linked to RAG1
- Combined immunodeficiency due to partial RAG1 deficiency, also linked to RAG1
Frequently asked questions
Which genes are linked to Recombinase activating gene 1 deficiency?
In CATVariant, Recombinase activating gene 1 deficiency is linked to 1 analyzed protein: RAG1 (V(D)J recombination-activating protein 1).
How many genetic variants are linked to Recombinase activating gene 1 deficiency?
41 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.
Which uncertain variants in Recombinase activating gene 1 deficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Recombinase activating gene 1 deficiency?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 8 disease-causing and 18 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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