Recombinase activating gene 2 deficiency: genes and variants

Genes linked to Recombinase activating gene 2 deficiency

• RAG2: V(D)J recombination-activating protein 2

  Together with RAG1, it restricts and activates V(D)J recombination during lymphocyte development so immunoglobulin and T-cell receptor genes can be assembled. Biallelic loss-of-function variants cause severe combined immunodeficiency or hypomorphic immune-dysregulation syndromes.

  25 disease-causing and 22 uncertain variants in RAG2 are linked to Recombinase activating gene 2 deficiency.

Where Recombinase activating gene 2 deficiency variants cluster

• RAG2 PHD-type (positions 416–484): 11 of 25 disease-causing changes, 3.4× more than its size predicts.

Known disease-causing variants in Recombinase activating gene 2 deficiency

Which prediction tools work for Recombinase activating gene 2 deficiency

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• SIFT: 100 out of 100
• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 97 out of 100
• phyloP: 90 out of 100

Same protein, different disease

• Combined immunodeficiency with skin granulomas is also caused by RAG2 variants; they fall partly in the same places as the Recombinase activating gene 2 deficiency variants (33 disease-causing).
• Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive is also caused by RAG2 variants; they fall partly in the same places as the Recombinase activating gene 2 deficiency variants (32 disease-causing).
• Histiocytic medullary reticulosis is also caused by RAG2 variants; they fall in the same places as the Recombinase activating gene 2 deficiency variants (14 disease-causing).
• Severe combined immunodeficiency disease is also caused by RAG2 variants; they fall partly in the same places as the Recombinase activating gene 2 deficiency variants (7 disease-causing).

Diseases related to Recombinase activating gene 2 deficiency

• Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, also linked to RAG2
• Combined immunodeficiency with skin granulomas, also linked to RAG2
• Severe combined immunodeficiency disease, also linked to RAG2
• Histiocytic medullary reticulosis, also linked to RAG2
• Inborn error of immunity, also linked to RAG2
• Common variable immunodeficiency, also linked to RAG2

Frequently asked questions

Which genes are linked to Recombinase activating gene 2 deficiency?

In CATVariant, Recombinase activating gene 2 deficiency is linked to 1 analyzed protein: RAG2 (V(D)J recombination-activating protein 2).

How many genetic variants are linked to Recombinase activating gene 2 deficiency?

61 variants: 25 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 22 are of uncertain significance or have conflicting reports.

Which uncertain variants in Recombinase activating gene 2 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 2 deficiency?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 25 disease-causing and 9 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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