KAT6A (Lysine Acetyltransferase 6A) Gene
KAT6A encodes a histone acetyltransferase involved in chromatin remodeling, transcriptional regulation, and neurodevelopment; mutations cause KAT6A syndrome and are implicated in cancer.
Gene Information Card
| Symbol | KAT6A |
|---|---|
| Full Name | Lysine Acetyltransferase 6A |
| Gene Type | Protein coding |
| Chromosomal Location | 8p11.21 |
| NCBI Gene ID | 8415 ncbi.nlm.nih.gov/gene/8415 |
| Ensembl ID | ENSG00000083168 |
| UniProt ID | Q92794 |
| OMIM ID | 601408 |
| HGNC ID | 13013 |
| Aliases | MOZ, MYST3, ZC2HC6A, RUNXBP2 |
Description
The KAT6A gene encodes a histone acetyltransferase that belongs to the MYST family. It plays a critical role in chromatin remodeling and transcriptional regulation by acetylating histone and non-histone proteins. KAT6A is essential for normal development, particularly of the brain and heart. Mutations in KAT6A are associated with KAT6A syndrome (a neurodevelopmental disorder) and have been implicated in various cancers, including acute myeloid leukemia and mixed-lineage leukemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| KAT6A syndrome (autosomal dominant intellectual disability) | Haploinsufficiency due to loss-of-function mutations (nonsense, frameshift, splice site) leading to reduced KAT6A protein levels and impaired histone acetylation. | ClinVar: Pathogenic variants; OMIM #616268; multiple case reports. |
| Acute myeloid leukemia (AML) | Chromosomal translocations (e.g., t(8;16)(p11;p13)) creating KAT6A-CBP fusion proteins with aberrant acetyltransferase activity, disrupting gene expression. | COSMIC: Fusion genes; literature evidence. |
| Mixed-lineage leukemia (MLL) | KAT6A rearrangements (e.g., t(8;22)) leading to fusion proteins that alter transcriptional regulation. | COSMIC: Gene fusions; literature evidence. |
| Breast cancer | KAT6A overexpression or amplification may promote tumorigenesis via histone acetylation and activation of oncogenic pathways. | COSMIC: Copy number alterations; literature evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | High (approx. 20-30 nTPM) | High expression in neural tissues. |
| Heart | Moderate (approx. 10-20 nTPM) | Moderate expression. |
| Testis | Moderate (approx. 10-20 nTPM) | Moderate expression. |
| Liver | Low (approx. 5-10 nTPM) | Low expression. |
| Kidney | Low (approx. 5-10 nTPM) | Low expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | High (approx. 30 nTPM) | Leukemia cell line with KAT6A expression. |
| HeLa (cervical cancer) | Moderate (approx. 15 nTPM) | Moderate expression. |
| A549 (lung cancer) | Moderate (approx. 12 nTPM) | Moderate expression. |
| MCF7 (breast cancer) | Moderate (approx. 10 nTPM) | Moderate expression. |
| HepG2 (liver cancer) | Low (approx. 5 nTPM) | Low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3460C>T (p.Arg1154Ter) | Nonsense | Rare (found in KAT6A syndrome patients) | Loss-of-function; premature stop codon leading to truncated protein and haploinsufficiency. |
| c.2200_2201del (p.Leu734ValfsTer26) | Frameshift | Rare (found in KAT6A syndrome patients) | Loss-of-function; frameshift leading to truncated protein. |
| c.1567+1G>A | Splice site | Rare (found in KAT6A syndrome patients) | Loss-of-function; aberrant splicing leading to reduced protein. |
| t(8;16)(p11;p13) KAT6A-CBP fusion | Chromosomal translocation | Recurrent in AML | Gain-of-function; fusion protein with aberrant acetyltransferase activity. |
| t(8;22)(p11;q13) KAT6A-EP300 fusion | Chromosomal translocation | Rare in AML | Gain-of-function; fusion protein with aberrant acetyltransferase activity. |
Mutation functional classification
Loss of Function (LOF)
Most KAT6A syndrome mutations are loss-of-function (nonsense, frameshift, splice site) leading to haploinsufficiency. These reduce histone acetyltransferase activity and disrupt normal gene expression, causing neurodevelopmental defects.
Gain of Function (GOF)
Chromosomal translocations in leukemia create KAT6A fusion proteins (e.g., KAT6A-CBP) that exhibit gain-of-function activity, often with increased or altered acetyltransferase activity, leading to aberrant transcriptional activation and oncogenesis.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner, but evidence is limited. Most pathogenic variants are loss-of-function; dominant-negative effects are not well established for KAT6A.
View complete mutation data：
Gene Ontology (GO)
| • Histone acetyltransferase activity | • Chromatin binding |
| • Transcription coactivator activity | • Regulation of transcription |
| • DNA-templated | • Chromatin remodeling |
| • Cell differentiation | • Neurogenesis |
| • Heart development |
Pathways
• Chromatin organization
• Transcriptional regulation by histone acetylation
• Notch signaling (modulation)
• p53/TP53 pathway (regulation)
• RUNX1-mediated transcription (interaction)
Protein Summary
KAT6A is a large protein (approximately 2004 amino acids) that contains a MYST catalytic domain, a PHD-type zinc finger, and an acidic domain. It functions as a histone acetyltransferase, primarily acetylating histone H3 at lysine 9 (H3K9) and lysine 14 (H3K14), and also acetylates non-histone proteins such as p53. KAT6A is part of the MOZ/MORF complex, which is involved in transcriptional activation. It plays a crucial role in embryonic development, hematopoiesis, and neurogenesis. Mutations lead to KAT6A syndrome with intellectual disability, speech delay, and cardiac anomalies. In cancer, KAT6A fusions drive leukemogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KAT6A Knockout HEK293 Cell Line | EDJ-KQ1108 | Human | 7994 | Details Get a Quote |
| KAT6A Knockout A-549 Cell Line | EDJ-KQ20291 | Human | 7994 | Details Get a Quote |
| KAT6A Knockout HCT 116 Cell Line | EDJ-KQ20292 | Human | 7994 | Details Get a Quote |
| KAT6A Knockout HeLa Cell Line | EDJ-KQ20293 | Human | 7994 | Details Get a Quote |
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