Combined immunodeficiency due to partial RAG1 deficiency: genes and variants

Genes linked to Combined immunodeficiency due to partial RAG1 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.

  13 disease-causing and 15 uncertain variants in RAG1 are linked to Combined immunodeficiency due to partial RAG1 deficiency.

Known disease-causing variants in Combined immunodeficiency due to partial RAG1 deficiency

Which prediction tools work for Combined immunodeficiency due to partial RAG1 deficiency

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

• REVEL: 100 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
• PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 85 out of 100

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 Combined immunodeficiency due to partial RAG1 deficiency variants (52 disease-causing).
• Combined immunodeficiency with skin granulomas is also caused by RAG1 variants; they fall mostly in different places as the Combined immunodeficiency due to partial RAG1 deficiency variants (49 disease-causing).
• Histiocytic medullary reticulosis is also caused by RAG1 variants; they fall mostly in different places as the Combined immunodeficiency due to partial RAG1 deficiency variants (11 disease-causing).
• Severe combined immunodeficiency disease is also caused by RAG1 variants; they fall partly in the same places as the Combined immunodeficiency due to partial RAG1 deficiency variants (8 disease-causing).
• Recombinase activating gene 1 deficiency is also caused by RAG1 variants; they fall mostly in different places as the Combined immunodeficiency due to partial RAG1 deficiency variants (8 disease-causing).

Diseases related to Combined immunodeficiency due to partial RAG1 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
• Recombinase activating gene 1 deficiency, also linked to RAG1

Frequently asked questions

Which genes are linked to Combined immunodeficiency due to partial RAG1 deficiency?

In CATVariant, Combined immunodeficiency due to partial RAG1 deficiency is linked to 1 analyzed protein: RAG1 (V(D)J recombination-activating protein 1).

How many genetic variants are linked to Combined immunodeficiency due to partial RAG1 deficiency?

61 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 15 are of uncertain significance or have conflicting reports.

Which uncertain variants in Combined immunodeficiency due to partial RAG1 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 Combined immunodeficiency due to partial RAG1 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 13 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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