DNMT1 Gene: DNA Methyltransferase 1 – Function, Mutations, and Disease Associations
Comprehensive guide to DNMT1: genomic location, protein function, expression, mutations, and associated disorders including hereditary sensory neuropathy and cancer.
Gene Information Card
| Symbol | DNMT1 |
|---|---|
| Full Name | DNA methyltransferase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 1786 ncbi.nlm.nih.gov/gene/1786 |
| Ensembl ID | ENSG00000130816 |
| UniProt ID | P26358 |
| OMIM ID | 126375 |
| HGNC ID | 2976 |
| Aliases | ADCADN, CXXC9, DNMT, MCMT, HSN1E |
Description
The DNMT1 gene encodes DNA methyltransferase 1, a key enzyme responsible for maintaining DNA methylation patterns during DNA replication. It catalyzes the transfer of methyl groups to cytosine residues in CpG dinucleotides, thereby regulating gene expression, genomic stability, and chromatin structure. DNMT1 is essential for normal development and cellular differentiation, and its dysfunction is linked to various neurological disorders and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory neuropathy type IE (HSN1E) | Mutations in DNMT1 cause reduced methyltransferase activity, leading to aberrant DNA methylation and neuronal dysfunction. | ClinVar, OMIM |
| Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) | DNMT1 mutations disrupt methylation maintenance in neurons, contributing to neurodegeneration. | OMIM, PubMed |
| Colorectal cancer | Somatic DNMT1 overexpression or altered activity contributes to aberrant methylation of tumor suppressor genes. | COSMIC, PubMed |
| Breast cancer | DNMT1 upregulation is associated with hypermethylation of tumor suppressor promoters, promoting tumorigenesis. | COSMIC, PubMed |
| Lung cancer | DNMT1 mutations and overexpression are observed, affecting methylation patterns in oncogenes and tumor suppressors. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 20.1 | High |
| Lung | 12.3 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 9.8 | Medium |
| Colon | 8.7 | Medium |
| Breast | 7.2 | Low |
| Heart | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| A549 | 12.8 | Lung carcinoma; moderate expression |
| MCF7 | 9.4 | Breast cancer; moderate expression |
| HepG2 | 11.1 | Liver cancer; moderate expression |
| K562 | 8.3 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asp490Glu | Missense | Rare | Reduced enzyme activity, associated with HSN1E |
| p.Val606Phe | Missense | Rare | Impaired methylation, linked to ADCA-DN |
| p.Arg569Cys | Missense | Rare | Dominant negative effect, causes neurodegeneration |
| p.Gly605Ala | Missense | Rare | Altered substrate binding, associated with HSN1E |
| p.Pro582Leu | Missense | Rare | Reduced stability, linked to ADCA-DN |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Asp490Glu and p.Val606Phe reduce DNMT1 enzymatic activity, leading to global hypomethylation and genomic instability.
Gain of Function (GOF)
Some somatic mutations in cancer may lead to increased DNMT1 activity, causing hypermethylation of tumor suppressor genes.
Dominant Negative (DN)
Mutations like p.Arg569Cys produce a dominant negative effect, interfering with the wild-type enzyme's function and disrupting methylation patterns.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • DNA (cytosine-5-)-methyltransferase activity |
| • methyltransferase activity | • zinc ion binding |
| • chromatin binding | • regulation of gene expression |
| • DNA methylation | • cell cycle |
| • apoptotic process | • nervous system development |
Pathways
• DNA methylation
• Epigenetic regulation of gene expression
• Cytosine methylation
• Maintenance of methylation patterns during replication
Protein Summary
DNMT1 is a large multidomain protein (1616 amino acids) that localizes to replication foci during S-phase, where it methylates newly synthesized DNA. It contains an N-terminal regulatory domain with a PCNA-binding motif, a CXXC zinc finger domain, and a C-terminal catalytic domain. The protein interacts with multiple partners including UHRF1, which recruits it to hemimethylated sites. DNMT1 is essential for maintaining epigenetic stability, and its dysregulation is implicated in cancer and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNMT1 Knockout HAP1 Cell Line | EDJ-KQ78106 | Human | 1786 | Details Get a Quote |
| DNMT1 Knockout HEK293T Cell Line | EDJ-KQ78134 | Human | 1786 | Details Get a Quote |
| DNMT1 Knockout HCT 116 Cell Line | EDJ-KQ78135 | Human | 1786 | Details Get a Quote |
