SPI1 (Transcription factor PU.1) variants and mutations

SPI1 (also known as Transcription factor PU.1) is a human protein-coding gene encoding a transcription factor PU.1 protein. 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. This analysis covers 595 SPI1 variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes agammaglobulinemia 10, autosomal dominant, agammaglobulinemia, and neurodegenerative disease. Example SPI1 variants include L2F, L2I, and Q3*.

Variant analysis overview

Gene: SPI1
Protein: Transcription factor PU.1
UniProt accession: P17947
Organism: Homo sapiens
Variants analyzed: 595
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 309 unspecified-consequence records; 4 stop lost; 1 stop retained variant; 162 missense variants; 74 synonymous variants; 27 frameshift variants; 9 stop-gained variants; 7 in-frame deletions; 1 in-frame insertions; 1 protein altering variant
Prediction scores: 479 variants have prediction scores (81% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: agammaglobulinemia 10, autosomal dominant, agammaglobulinemia, neurodegenerative disease, Alzheimer disease, autosomal agammaglobulinemia, multiple sclerosis, Parkinson disease, lysosomal storage disease, hypertensive disorder, acute myeloid leukemia, essential hypertension, Increased blood pressure.

Protein structure and variant hotspots

Protein features: 4 binding sites; 2 post-translational modification sites.
PTM context: 1 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable SPI1 variants

Examples include L2F, L2I, Q3*, Q3E, Q3P, Q3R, A4E, A4T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SPI1 analysis run — SPI1 (595 variants) — completed 2026-08-20