KMT2B

Chr 19AD

lysine methyltransferase 2B

Also known as: CXXC10, DYT28, HRX2, MLL1B, MLL2, MLL4, MRD68, TRX2

The KMT2B protein is a histone methyltransferase that contains a SET domain and functions as a transcriptional regulator through chromatin modification. Loss-of-function mutations cause autosomal dominant childhood-onset dystonia (dystonia 28) and intellectual developmental disorder, with haploinsufficiency being the underlying pathogenic mechanism. The condition typically presents with progressive dystonia beginning in childhood and may be associated with developmental delays.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD2 OMIM phenotypes
Clinical SummaryKMT2B
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder with motor features · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — KMT2B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

Constraint data not available from gnomAD.

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongKMT2B-related complex early-onset dystoniaLOFAD
DN
0.16100th %ile
GOF
0.2597th %ile
LOF
0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation

Literature Evidence

LOFMost mutations are de novo and expected to mediate epigenetic dysregulation by inducing KMT2B haploinsufficiency.PMID:31768667

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KMT2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Dystonia.
Balint B et al.·Nat Rev Dis Primers
2018Review
Genetics and Pathogenesis of Dystonia.
Thomsen M et al.·Annu Rev Pathol
2024Review
Update on KMT2B-Related Dystonia.
Zech M et al.·Curr Neurol Neurosci Rep
2019Review
Top 5 results · since 2015Search PubMed ↗