Combined immunodeficiency: genes and variants
Combined immunodeficiency is linked to 2 analyzed proteins (IL2RG and BCL11B). 2 DNA variants are known to cause it; 2 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: combined immunodeficiency, X-linked
Genes linked to Combined immunodeficiency
IL2RG: Cytokine receptor common subunit gamma
It is the shared signaling chain used by receptors for several interleukins required for lymphocyte development and survival. Loss-of-function variants cause X-linked severe combined immunodeficiency with profound T-cell and natural-killer-cell deficiency.
1 disease-causing and 1 uncertain variants in IL2RG are linked to Combined immunodeficiency.
BCL11B: B-cell lymphoma/leukemia 11B
It regulates transcriptional programs required for T-cell development, craniofacial development, and nervous-system maturation. Heterozygous pathogenic variants can cause a syndromic neurodevelopmental disorder with immunologic abnormalities and variable craniofacial features.
1 disease-causing and 0 uncertain variants in BCL11B are linked to Combined immunodeficiency.
Weakly linked (only a few uncertain records): POLD1 and TFRC.
Known disease-causing variants in Combined immunodeficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| IL2RG Y125C | 125 | Extracellular | Disease-causing (★) |
| BCL11B N441K | 441 | C2H2-type 2 | Disease-causing |
Same protein, different disease
- X-linked severe combined immunodeficiency is also caused by IL2RG variants; they fall mostly in different places as the Combined immunodeficiency variants (30 disease-causing).
- Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities is also caused by BCL11B variants; they fall mostly in different places as the Combined immunodeficiency variants (3 disease-causing).
Diseases related to Combined immunodeficiency
- X-linked severe combined immunodeficiency, also linked to IL2RG
- Renal cell carcinoma, also linked to IL2RG
- Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, also linked to BCL11B
Frequently asked questions
Which genes are linked to Combined immunodeficiency?
In CATVariant, Combined immunodeficiency is linked to 2 analyzed proteins: IL2RG (Cytokine receptor common subunit gamma) and BCL11B (B-cell lymphoma/leukemia 11B).
How many genetic variants are linked to Combined immunodeficiency?
13 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Combined immunodeficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
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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