Agammaglobulinemia: genes and variants
Agammaglobulinemia is linked to 4 analyzed proteins (SPI1, PIK3R1, CD79B and CD79A). 4 DNA variants are known to cause it; 308 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: agammaglobulinemia 10, autosomal dominant; Agammaglobulinemia 3, autosomal recessive; Agammaglobulinemia 6, autosomal recessive; agammaglobulinemia 7, autosomal recessive
Genes linked to Agammaglobulinemia
SPI1: Transcription factor PU.1
It directs transcriptional programs required for myeloid and B-cell development. Altered dosage can block differentiation and cooperate in leukemia, while rare germline variants can cause immunodeficiency or predisposition to myeloid disease.
3 disease-causing and 2 uncertain variants in SPI1 are linked to Agammaglobulinemia.
PIK3R1: Phosphatidylinositol 3-kinase regulatory subunit alpha
Its p85-family products stabilize and regulate class IA PI3K catalytic subunits and couple receptors to PI3K activation. Pathogenic variants can cause activated PI3K-delta syndrome type 2 or SHORT syndrome depending on how they alter pathway output.
0 disease-causing and 189 uncertain variants in PIK3R1 are linked to Agammaglobulinemia.
CD79B: B-cell antigen receptor complex-associated protein beta chain
Together with CD79A, it transduces signals from surface immunoglobulin into B cells through immunoreceptor tyrosine-based activation motifs. Somatic activating mutations are common in certain diffuse large B-cell lymphomas and promote chronic B-cell receptor signaling.
1 disease-causing and 48 uncertain variants in CD79B are linked to Agammaglobulinemia.
CD79A: B-cell antigen receptor complex-associated protein alpha chain
Together with CD79B, it carries the intracellular signaling motifs that allow the B-cell receptor to transmit antigen-binding signals. Biallelic loss-of-function variants can block B-cell development and cause agammaglobulinemia.
0 disease-causing and 69 uncertain variants in CD79A are linked to Agammaglobulinemia.
Known disease-causing variants in Agammaglobulinemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SPI1 H211P | 211 | ETS | Disease-causing (★) |
| SPI1 V241G | 241 | ETS | Disease-causing (★) |
| CD79B G137S | 137 | Ig-like V-type | Disease-causing |
| SPI1 F53L | 53 | Disease-causing |
Diseases related to Agammaglobulinemia
- Inherited Immunodeficiency Diseases, also linked to CD79A
- Vascular malformation, also linked to PIK3R1
- CLOVES syndrome, also linked to PIK3R1
- PIK3R1-related immunodeficiency and SHORT syndrome, also linked to PIK3R1
Frequently asked questions
Which genes are linked to Agammaglobulinemia?
In CATVariant, Agammaglobulinemia is linked to 4 analyzed proteins: SPI1 (Transcription factor PU.1), PIK3R1 (Phosphatidylinositol 3-kinase regulatory subunit alpha), CD79B (B-cell antigen receptor complex-associated protein beta chain) and CD79A (B-cell antigen receptor complex-associated protein alpha chain).
How many genetic variants are linked to Agammaglobulinemia?
409 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 308 are of uncertain significance or have conflicting reports.
Which uncertain variants in Agammaglobulinemia 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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