DNMT1

DNA methyltransferase 1

2 disorders 1 causative 1 untyped 19p13.2 gene with protein product

HGNC:2976 Monarch NCBI Gene 1786 ENSG00000130816 UniProt P26358 OMIM 126375

Previous symbols: DNMT. Aliases: MCMT, CXXC9.

Normal function · from ai-gene-review (P26358, commit 79fe13b38970) · AI-generated, not KB evidence

DNMT1 is the predominant mammalian maintenance DNA methyltransferase responsible for preserving CpG methylation patterns during DNA replication. It plays essential roles in genomic imprinting, X-chromosome inactivation, heterochromatin formation, and silencing of repetitive elements. The protein contains multiple regulatory domains including RFTS, CXXC, BAH domains and a C-terminal catalytic domain that uses SAM as methyl donor to methylate cytosine residues in CpG dinucleotides, with 2-fold preference for hemimethylated sites.

DNMT1 catalyzes the methylation of cytosine residues at the 5-position in CpG dinucleotides using S-adenosyl-L-methionine as methyl donor, with 2-fold preference for hemimethylated sites during DNA replication. This is the primary enzymatic activity that defines DNMT1 as the maintenance DNA methyltransferase, essential for preserving genomic methylation patterns during cell division.

molecular function: DNA (cytosine-5-)-methyltransferase activity

DNMT1 maintains genomic methylation patterns during DNA replication through UHRF1-mediated recruitment to hemimethylated CpG sites, ensuring faithful epigenetic inheritance. This process is fundamental to cellular identity maintenance and involves precise targeting to newly replicated DNA strands.

molecular function: DNA (cytosine-5-)-methyltransferase activity

DNMT1 silences gene expression through CpG island hypermethylation at promoter regions, leading to recruitment of methyl-CpG binding proteins and chromatin remodeling complexes that establish repressive chromatin states. This function is critical for maintaining tissue-specific gene expression patterns and preventing inappropriate gene activation.

molecular function: DNA (cytosine-5-)-methyltransferase activity

DNMT1 maintains heterochromatin structure and genomic stability through methylation of repetitive elements, satellite sequences, and pericentromeric regions. This function is essential for chromosome stability, preventing transposon activation, and proper chromosome segregation during cell division.

molecular function: DNA (cytosine-5-)-methyltransferase activity

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Autosomal Dominant Cerebellar Ataxia Deafness and Narcolepsy	causative germline	mechanism: Aberrant DNMT1-NSUN2 RNA m5C Methylation; DNMT1 Exon 21 RFTS Domain Missense Variant animal model: Mouse (Mus musculus)
Hereditary Sensory and Autonomic Neuropathy Type 1E	untyped Causal

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.