KMT2B

Chr 19AD

lysine methyltransferase 2B

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

NCBI Gene: 9757ENSG00000272333UniProt: Q9UMN6

This gene encodes a protein which contains multiple domains including a CXXC zinc finger, three PHD zinc fingers, two FY-rich domains, and a SET (suppressor of variegation, enhancer of zeste, and trithorax) domain. The SET domain is a conserved C-terminal domain that characterizes proteins of the MLL (mixed-lineage leukemia) family. This gene is ubiquitously expressed in adult tissues. It is also amplified in solid tumor cell lines, and may be involved in human cancer. Two alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene, however, the full length nature of the shorter transcript is not known. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Dystonia 28, childhood-onsetMIM #617284
AD
Intellectual developmental disorder, autosomal dominant 68MIM #619934
AD
658
ClinVar variants
19
Pathogenic / LP
—
pLI score
1
Active trials
Clinical Summary— KMT2B
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder with motor features · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 340 VUS of 658 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

658 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic7
VUS340
Likely Benign229
Benign60
Conflicting10
12
Pathogenic
7
Likely Pathogenic
340
VUS
229
Likely Benign
60
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
1
0
12
Likely Pathogenic
3
2
2
0
7
VUS
1
319
17
3
340
Likely Benign
0
36
74
119
229
Benign
0
26
2
32
60
Conflicting
—10
Total1538396154658

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

KMT2B-related complex early-onset dystonia

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dystonia 28, childhood-onset

MIM #617284

Molecular basis of disorder known

Autosomal dominant

Intellectual developmental disorder, autosomal dominant 68

MIM #619934

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — KMT2B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
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
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
Pérez-Dueñas B et al.·Mov Disord
2022
KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.
Cif L et al.·Brain
2020
Update on KMT2B-Related Dystonia.
Zech M et al.·Curr Neurol Neurosci Rep
2019Review
Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders.
Faundes V et al.·Am J Hum Genet
2018
Methylation assay in KMT2B-related dystonia: a novel diagnostic validation tool.
da Silva Carvalho GF et al.·Clin Epigenetics
2024
Clinical phenotypes, genotypes and treatment in Chinese dystonia patients with KMT2B variants.
Li XY et al.·Parkinsonism Relat Disord
2020Cohort
Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases.
Marogianni C et al.·Mol Biol Rep
2021Meta-analysis
Update on the Genetics of Dystonia.
Lohmann K et al.·Curr Neurol Neurosci Rep
2017Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
DystoniaMovement DisordersCombined Dystonia

Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia

NOT YET RECRUITING
NCT06999096Phase NAUniversity Hospital, Strasbourg, FranceStarted 2025-08
Long-read whole genome sequencing

External Resources

Links to major genomics databases and tools