DNMT1 gene
The DNMT1 gene provides instructions for making an enzyme essential for DNA methylation, a process that regulates gene expression and cellular function.
Normal Function
The DNMT1 gene provides instructions for making an enzyme called DNA methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups—consisting of one carbon atom and three hydrogen atoms—to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines.
DNA methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and fats (lipids), and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). DNA methyltransferase 1 is active in the adult nervous system. Although its specific function is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to move (migrate) and connect with each other, and neuron survival.
Health Conditions Related to Genetic Changes
Autosomal dominant cerebellar ataxia, deafness, and narcolepsy
At least four DNMT1 gene mutations have been identified in people with a nervous system disorder called autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCADN). Features of this disorder include:
- Difficulty coordinating movements (ataxia)
- Hearing loss caused by abnormalities of the inner ear (sensorineural deafness)
- Excessive daytime sleepiness (narcolepsy)
- Cognitive decline as the disorder progresses
- Numbness, tingling, or pain in the arms and legs (sensory neuropathy)
Affected individuals usually survive into their forties or fifties. The mutations associated with this disorder affect a region of the DNA methyltransferase 1 enzyme known as the targeting sequence, which helps direct the methylation process to the correct segments of DNA. As a result, methylation is abnormal, affecting the expression of multiple genes and disrupting the maintenance of neurons.
Hereditary sensory and autonomic neuropathy type IE
At least 10 DNMT1 gene mutations have been identified in people with hereditary sensory and autonomic neuropathy type IE (HSAN IE). Similar to ADCADN, individuals with HSAN IE experience sensorineural deafness, sensory neuropathy, cognitive decline, and a shortened lifespan. However, they typically do not have the ataxia or narcolepsy seen in ADCADN, and the sensory neuropathy begins earlier in life. Seizures can also occur.
Most mutations causing HSAN IE occur in exon 20, while those causing ADCADN are mostly in exon 21. Both affect the enzyme's targeting sequence, leading to abnormal methylation and impaired neuronal maintenance.
Charcot-Marie-Tooth disease
The DNMT1 gene is also associated with Charcot-Marie-Tooth disease.
Cancers
Several normal variations (polymorphisms) in the DNMT1 gene have been associated with an increased risk of cancer, including cancers of the breast and stomach. These variations may affect the enzyme's role in gene silencing, leading to abnormal cell growth and division.
Additionally, increased activity (overexpression) of the DNMT1 gene has been identified in certain brain cancers called gliomas. These somatic genetic changes occur only in tumor cells and may result in the silencing of tumor suppressor genes, allowing cells to grow and divide unchecked.
Other Names for This Gene
- AIM
- CXXC finger protein 9
- CXXC-type zinc finger protein 9
- CXXC9
- DNA (cytosine-5)-methyltransferase 1
- DNA (cytosine-5-)-methyltransferase 1
- DNA methyltransferase HsaI
- DNA MTase HsaI
- DNMT
- DNMT1_HUMAN
- HSN1E
- m.HsaI
- MCMT