KMT2E (Histone reader KMT2E) variants and mutations

KMT2E (also known as Histone reader KMT2E) is a human protein-coding gene encoding a histone reader protein. It regulates chromatin and transcription through mechanisms distinct from the catalytic KMT2 methyltransferases and is important for brain development and cell-cycle control. Haploinsufficiency causes O'Donnell-Luria-Rodan syndrome, with developmental delay, intellectual disability, and frequently macrocephaly. This analysis covers 1,961 KMT2E variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes O'Donnell-Luria-Rodan syndrome, Intellectual disability, and hereditary disease. Example KMT2E variants include S2N, S2R, and I3L.

Variant analysis overview

Gene: KMT2E
Protein: Histone reader KMT2E
UniProt accession: Q8IZD2
Organism: Homo sapiens
Variants analyzed: 1961
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 1,822 unspecified-consequence records; 73 missense variants; 53 synonymous variants; 4 stop-gained variants; 3 frameshift variants; 3 splice-region variants; 1 in-frame insertions; 2 in-frame deletions
Prediction scores: 1,606 variants have prediction scores (82% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: O'Donnell-Luria-Rodan syndrome, Intellectual disability, hereditary disease, neurodegenerative disease, Global developmental delay, Seizure, complex neurodevelopmental disorder, autism, neurodevelopmental disorder, Neurodevelopmental delay, lysosomal storage disease, intelligence.

Protein structure and variant hotspots

Protein features: 1 domains; 8 binding sites; 8 post-translational modification sites.
Structural context: 77 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.

Notable KMT2E variants

Examples include S2N, S2R, I3L, I3M, I5F, I5N, I5S, P6A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

KMT2E analysis run — KMT2E (1,961 variants) — completed 2026-08-20