STAT6 (P42226) variants and mutations

STAT6 (also known as P42226) is a human protein-coding gene encoding a signal transducer and activator of transcription 6 protein. It mediates IL-4 and IL-13 signaling that drives type 2 immunity, IgE responses, and alternative macrophage activation. Gain-of-function germline variants can cause severe early-onset allergic disease and immune dysregulation, while pathway inhibition is therapeutically useful in atopic disorders. This analysis covers 1,190 STAT6 variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes hyper-IgE syndrome 6, autosomal dominant, with recurrent infections, asthma, and diffuse large B-cell lymphoma. Example STAT6 variants include M1?, W4*, and G5C.

Variant analysis overview

Gene: STAT6
Protein: P42226
UniProt accession: P42226
Organism: Homo sapiens
Variants analyzed: 1190
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 932 unspecified-consequence records; 1 stop lost; 1 stop retained variant; 93 synonymous variants; 15 frameshift variants; 135 missense variants; 2 in-frame insertions; 3 in-frame deletions; 5 stop-gained variants; 1 splice-region variants; 2 substitution
Prediction scores: 890 variants have prediction scores (75% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: hyper-IgE syndrome 6, autosomal dominant, with recurrent infections, asthma, diffuse large B-cell lymphoma, allergic disease, respiratory system disorder, allergic rhinitis, Wheezing, adult onset asthma, lymphoma, solitary fibrous tumor, childhood onset asthma, Hodgkins lymphoma.

Protein structure and variant hotspots

Protein features: 1 domains; 2 post-translational modification sites.
Structural context: 136 variants have structural context.
PTM context: 3 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 STAT6 variants

Examples include M1?, W4*, G5C, G5D, G5S, S8A, M10I, M10L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

STAT6 analysis run — STAT6 (1,190 variants) — completed 2026-08-19