SETD1B (Q9UPS6) variants and mutations

SETD1B (also known as Q9UPS6) is a human protein-coding gene encoding a histone-lysine N-methyltransferase protein. A histone methyltransferase that places H3K4 methyl marks and helps regulate gene expression. Pathogenic variants can cause a neurodevelopmental disorder with intellectual disability and seizures. This analysis covers 2,368 SETD1B variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes intellectual developmental disorder with seizures and language delay, hereditary disease, and neurodevelopmental disorder. Example SETD1B variants include E2D, E2Q, and N3S.

Variant analysis overview

Gene: SETD1B
Protein: Q9UPS6
UniProt accession: Q9UPS6
Organism: Homo sapiens
Variants analyzed: 2368
Variant scope: all variants
Completed: 2026-10-09

Variant and mutation evidence

Variant composition: 2,217 unspecified-consequence records; 93 missense variants; 102 synonymous variants; 6 in-frame deletions; 7 frameshift variants; 2 in-frame insertions; 2 splice-region variants; 1 stop-gained variants; 3 substitution
Prediction scores: 2,314 variants have prediction scores (98% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: intellectual developmental disorder with seizures and language delay, hereditary disease, neurodevelopmental disorder, complex neurodevelopmental disorder, autosomal dominant non-syndromic intellectual disability, Global developmental delay, Abnormality of the skeletal system, epilepsy, Neurodevelopmental delay, lung adenocarcinoma, head and neck squamous cell carcinoma, gastric adenocarcinoma.

Protein structure and variant hotspots

Protein features: 3 domains; 1 binding sites; 8 post-translational modification sites.
Structural context: 242 variants have structural context.
PTM context: 7 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Diseases linked to SETD1B

Notable SETD1B variants

Examples include E2D, E2Q, N3S, N3T, N3K, N3N, S4G, S4I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SETD1B analysis run — SETD1B (2,368 variants) — completed 2026-10-09