DNMT3A gene
The DNMT3A gene encodes an enzyme critical for establishing DNA methylation patterns during development and regulating blood cell maturation.
Normal Function
The DNMT3A gene provides instructions for making an enzyme called DNA methyltransferase 3 alpha. This enzyme is involved in DNA methylation, the addition of methyl groups to DNA molecules, specifically at cytosines. This process is vital for gene silencing, regulating lipid and protein reactions, and controlling neurotransmitter signaling.
DNA methyltransferase 3 alpha is particularly important for establishing DNA methylation patterns during development before birth. It also functions in early cells, such as hematopoietic stem cells, where it promotes maturation (differentiation) into various blood cell types.
Health Conditions Related to Genetic Changes
DNMT3A overgrowth syndrome
At least 16 mutations in the DNMT3A gene cause DNMT3A overgrowth syndrome. This condition is characterized by:
- Faster than normal growth before and after birth
- Distinctive facial appearance
- Intellectual disability
These mutations, found in all body cells, lead to a decrease in normal enzyme function and a reduction in DNA methylation. This disrupts the regulation of important developmental genes. In some cases, the entire DNMT3A gene and neighboring genes are deleted.
Cytogenetically normal acute myeloid leukemia
Mutations in the DNMT3A gene are associated with cytogenetically normal acute myeloid leukemia (CN-AML), a form of blood cancer. Up to one-third of people with CN-AML have a somatic mutation in this gene.
These mutations are not inherited and typically change single amino acids in the enzyme, making it less able to fully methylate DNA. This altered methylation pattern may turn on genes that are normally silenced, preventing hematopoietic stem cells from differentiating normally and leading to the overproduction of immature white blood cells.
Systemic mastocytosis
The DNMT3A gene is also associated with systemic mastocytosis.
Other cancers
Somatic DNMT3A gene mutations are also found in T-cell acute lymphoblastic leukemia. These mutations disrupt normal methylation patterns, blocking cell differentiation in a manner similar to that seen in acute myeloid leukemia.
Other Names for This Gene
- DNA (cytosine-5)-methyltransferase 3A
- DNA (cytosine-5-)-methyltransferase 3 alpha
- DNA cytosine methyltransferase 3A2
- DNA MTase HsaIIIA
- DNM3A_HUMAN
- DNMT3A2
- M.HsaIIIA