KDM6B (Lysine-specific demethylase 6B) variants and mutations

KDM6B (also known as Lysine-specific demethylase 6B) is a human protein-coding gene encoding a lysine-specific demethylase 6B protein. It removes repressive H3K27 methylation and helps activate developmental, inflammatory, and differentiation programs. Heterozygous pathogenic variants can cause a neurodevelopmental disorder with intellectual disability and variable craniofacial or skeletal features. This analysis covers 2,502 KDM6B variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes neurodevelopmental disorder with coarse facies and mild distal skeletal abnormal, hereditary disease, and syndromic intellectual disability. Example KDM6B variants include H2R, H2Y, and R3Q.

Variant analysis overview

Gene: KDM6B
Protein: Lysine-specific demethylase 6B
UniProt accession: O15054
Organism: Homo sapiens
Variants analyzed: 2502
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 2,334 unspecified-consequence records; 83 synonymous variants; 70 missense variants; 1 stop-gained variants; 5 in-frame deletions; 1 in-frame insertions; 4 splice-region variants; 1 frameshift variants; 3 substitution
Prediction scores: 1,816 variants have prediction scores (73% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: neurodevelopmental disorder with coarse facies and mild distal skeletal abnormal, hereditary disease, syndromic intellectual disability, autosomal recessive non-syndromic intellectual disability, Neurodevelopmental abnormality, Neurodevelopmental delay, Intellectual disability, autism spectrum disorder, Abnormality of the skeletal system, arthropathy, developmental disability, musculoskeletal system disorder.

Protein structure and variant hotspots

Protein features: 1 domains; 7 binding sites; 1 post-translational modification sites.
Structural context: 144 variants have structural context.
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, ClinGen, MaveDB, LitVar.

Notable KDM6B variants

Examples include H2R, H2Y, R3Q, R3W, R3R, A4E, A4S, A4V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

KDM6B analysis run — KDM6B (2,502 variants) — completed 2026-08-20