KMT2A (Lysine Methyltransferase 2A)
A key epigenetic regulator in hematopoiesis and leukemia
Gene Information Card
| Symbol | KMT2A |
|---|---|
| Full Name | Lysine Methyltransferase 2A |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 4297 ncbi.nlm.nih.gov/gene/4297 |
| Ensembl ID | ENSG00000118058 |
| UniProt ID | Q03164 |
| OMIM ID | 159555 |
| HGNC ID | 7132 |
| Aliases | MLL, ALL-1, CXXC7, HRX, HTRX1, MLL1, TRX1 |
Description
KMT2A (lysine methyltransferase 2A), also known as MLL, encodes a transcriptional coactivator that methylates histone H3 lysine 4 (H3K4). It is essential for normal hematopoiesis and embryonic development. Chromosomal rearrangements involving KMT2A are recurrent in acute leukemias, particularly in infant and therapy-related cases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute lymphoblastic leukemia (ALL) | KMT2A rearrangements (e.g., t(4;11)(q21;q23) producing KMT2A-AFF1 fusion) drive leukemogenesis by aberrant transcriptional activation | ClinVar, COSMIC |
| Acute myeloid leukemia (AML) | KMT2A partial tandem duplications (PTD) or fusions (e.g., KMT2A-MLLT3) alter H3K4 methylation and gene expression | ClinVar, COSMIC |
| Wiedemann-Steiner syndrome | Heterozygous loss-of-function mutations in KMT2A cause this autosomal dominant disorder with intellectual disability and hypertrichosis | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Whole blood | 8.3 | Low |
| Brain | 6.1 | Low |
| Lymph node | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 18.4 | High expression |
| HEK293 | 9.7 | Moderate expression |
| HeLa | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| KMT2A-AFF1 fusion | Chromosomal translocation | Common in infant ALL | Oncogenic fusion protein disrupts normal H3K4 methylation |
| KMT2A partial tandem duplication | Intragenic duplication | ~5-10% of AML | Gain-of-function leading to HOX gene overexpression |
| p.Arg3762* | Nonsense | Rare | Loss-of-function associated with Wiedemann-Steiner syndrome |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations in KMT2A reduce H3K4 methyltransferase activity, linked to Wiedemann-Steiner syndrome.
Gain of Function (GOF)
Partial tandem duplications (PTD) enhance HOX gene activation, contributing to AML.
Dominant Negative (DN)
Some KMT2A fusion proteins (e.g., KMT2A-AFF1) may act as dominant negatives by sequestering wild-type KMT2A complexes.
View complete mutation data：
Gene Ontology (GO)
| • Histone H3K4 methyltransferase activity | • Chromatin binding |
| • Transcription coactivator activity | • Regulation of transcription by RNA polymerase II |
| • Positive regulation of hematopoietic stem cell differentiation |
Pathways
• KMT2A-mediated H3K4 methylation
• HOX gene activation in hematopoiesis
• Mixed lineage leukemia (MLL) fusion protein signaling
Protein Summary
KMT2A (MLL) is a large multidomain protein (3969 amino acids) that catalyzes methylation of histone H3 lysine 4. It contains a SET domain responsible for methyltransferase activity, as well as AT-hooks, CXXC zinc finger, and PHD fingers that mediate DNA and chromatin binding. Proteolytic cleavage generates N-terminal (MLL-N) and C-terminal (MLL-C) fragments that associate to form a stable complex. Rearrangements of KMT2A are among the most common genetic alterations in acute leukemias.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KMT2A Knockout HEK293 Cell Line | EDJ-KQ50442 | Human | 4297 | Details Get a Quote |
| KMT2A Knockout HeLa Cell Line | EDJ-KQ53877 | Human | 4297 | Details Get a Quote |
| KMT2A Knockout A-549 Cell Line | EDJ-KQ62368 | Human | 4297 | Details Get a Quote |
| KMT2A Knockout HCT 116 Cell Line | EDJ-KQ70837 | Human | 4297 | Details Get a Quote |
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