PIK3R1 (P27986) variants and mutations

PIK3R1 (also known as P27986) is a human protein-coding gene encoding a phosphatidylinositol 3-kinase regulatory subunit alpha protein. 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. This analysis covers 1,967 PIK3R1 variants and mutations. Of these, 43% have computational variant effect predictions. Disease context includes SHORT syndrome, immunodeficiency 36 with lymphoproliferation, and agammaglobulinemia 7, autosomal recessive. Example PIK3R1 variants include M1?, S2R, and S2N.

Variant analysis overview

Gene: PIK3R1
Protein: P27986
UniProt accession: P27986
Organism: Homo sapiens
Variants analyzed: 1967
Variant scope: all variants
Completed: 2026-08-18

Variant and mutation evidence

Variant composition: 1,776 unspecified-consequence records; 9 frameshift variants; 88 missense variants; 86 synonymous variants; 3 in-frame deletions; 2 in-frame insertions; 3 substitution
Prediction scores: 853 variants have prediction scores (43% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: SHORT syndrome, immunodeficiency 36 with lymphoproliferation, agammaglobulinemia 7, autosomal recessive, cancer, autosomal agammaglobulinemia, activated PI3K-delta syndrome, bone development disease, endometrial cancer, isolated agammaglobulinemia, neurodegenerative disease, vascular malformation, hereditary disease.

Protein structure and variant hotspots

Protein features: 4 domains; 6 post-translational modification sites.
Structural context: 1,246 variants have structural context.
PTM context: 13 variants overlap post-translational modification sites.

Data sources

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

Notable PIK3R1 variants

Examples include M1?, S2R, S2N, S2S, A3D, A3A, A3T, A3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

PIK3R1 analysis run — PIK3R1 (1,967 variants) — completed 2026-08-18