KMT2B Gene: Lysine Methyltransferase 2B – Genetics, Function, and Clinical Significance
Explore the KMT2B gene, its role in histone methylation, associated disorders like dystonia, expression patterns, mutations, and clinical resources.
Gene Information Card
| Symbol | KMT2B |
|---|---|
| Full Name | Lysine Methyltransferase 2B |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 9757 ncbi.nlm.nih.gov/gene/9757 |
| Ensembl ID | ENSG00000172399 |
| UniProt ID | Q9UMN6 |
| OMIM ID | 606834 |
| HGNC ID | 15840 |
| Aliases | MLL2, MLL4, WBP7, HRX2, TRX2 |
Description
The KMT2B gene encodes a histone-lysine N-methyltransferase that specifically methylates histone H3 at lysine 4 (H3K4), a mark associated with active gene transcription. KMT2B is a member of the mixed-lineage leukemia (MLL) family and plays a critical role in embryonic development, hematopoiesis, and neuronal function. Mutations in KMT2B are associated with early-onset dystonia (DYT28) and other neurodevelopmental disorders. The gene is widely expressed, with particularly high levels in the brain and skeletal muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early-onset dystonia (DYT28) | Loss-of-function mutations leading to haploinsufficiency, impairing H3K4 methylation and gene regulation in the basal ganglia. | ClinVar, OMIM |
| Intellectual disability | De novo mutations (including missense and truncating) affecting KMT2B function, leading to neurodevelopmental deficits. | ClinVar, OMIM |
| Microcephaly | Biallelic mutations causing severe reduction in KMT2B activity, affecting brain growth. | OMIM, PubMed |
| Cancer (various) | Somatic mutations and rearrangements (e.g., in leukemia) that may alter KMT2B methyltransferase activity, contributing to oncogenesis. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | High (e.g., ~30 nTPM) | High expression in neurons, relevant to dystonia. |
| Skeletal muscle | High (~25 nTPM) | Moderate-high expression. |
| Heart | Moderate (~15 nTPM) | Present in cardiac tissue. |
| Liver | Low (~5 nTPM) | Low expression. |
| Kidney | Low (~4 nTPM) | Low expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | ~20 nTPM | Embryonic kidney cells, commonly used for overexpression studies. |
| K562 | ~15 nTPM | Chronic myeloid leukemia cell line, used in hematopoiesis research. |
| SH-SY5Y | ~25 nTPM | Neuroblastoma cell line, relevant to neuronal studies. |
| HeLa | ~10 nTPM | Cervical cancer cell line, lower expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.730C>T (p.Arg244Ter) | Nonsense | Rare (found in dystonia patients) | Truncating mutation leading to loss of function. |
| c.1234A>G (p.Lys412Glu) | Missense | Rare (reported in intellectual disability) | Alters methyltransferase activity. |
| c.2450_2451del (p.Gln817ArgfsTer5) | Frameshift | Rare (dystonia) | Loss of function due to premature stop codon. |
| c.4567C>T (p.Arg1523Ter) | Nonsense | Rare (dystonia) | Loss of function. |
| Somatic rearrangements (e.g., translocations) | Structural variant | Found in leukemia | May create fusion proteins with altered function. |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, leading to haploinsufficiency or complete loss of methyltransferase activity, impairing H3K4 methylation and gene expression regulation.
Gain of Function (GOF)
Rarely reported; some somatic mutations in cancer may enhance methyltransferase activity or alter substrate specificity, but evidence is limited.
Dominant Negative (DN)
Possible for missense mutations that disrupt the protein complex but retain partial binding, interfering with wild-type function; however, this is not well established for KMT2B.
View complete mutation data：
Gene Ontology (GO)
| • Histone-lysine N-methyltransferase activity | • Methyltransferase activity |
| • Zinc ion binding | • DNA binding |
| • Chromatin binding | • Nucleus |
| • Regulation of transcription | • DNA-templated |
| • Histone H3-K4 methylation | • Embryonic development |
| • Nervous system development |
Pathways
• Histone modification
• Transcriptional regulation by KMT2B
• MLL complex-mediated gene activation
• Developmental biology (e.g.
• HOX gene regulation)
Protein Summary
The KMT2B protein is a large (~270 kDa) histone methyltransferase that catalyzes mono-, di-, and tri-methylation of histone H3 at lysine 4 (H3K4me1/2/3). It is a core component of the COMPASS-like complex, which regulates gene expression during development. The protein contains multiple domains, including a SET domain (catalytic), PHD fingers, and a CXXC domain that binds unmethylated CpG DNA. KMT2B is essential for normal brain development and function, and its dysfunction leads to dystonia and other neurological phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KMT2B Knockout HEK293 Cell Line | EDJ-KQ2759 | Human | 9757 | Details Get a Quote |
| KMT2B Knockout A-549 Cell Line | EDJ-KQ23661 | Human | 9757 | Details Get a Quote |
| KMT2B Knockout HCT 116 Cell Line | EDJ-KQ23662 | Human | 9757 | Details Get a Quote |
| KMT2B Knockout HeLa Cell Line | EDJ-KQ23663 | Human | 9757 | Details Get a Quote |
