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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DNMT1
DNA methyltransferase 1
Chromosome 19 Β· 19p13.2
NCBI Gene: 1786Ensembl: ENSG00000130816.18HGNC: HGNC:2976UniProt: I6L9H2
879PubMed Papers
22Diseases
2Drugs
13Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA bindingpositive regulation of gene expressionnegative regulation of gene expressionnegative regulation of gene expression via chromosomal CpG island methylationautosomal dominant cerebellar ataxia, deafness and narcolepsyhereditary sensory neuropathy-deafness-dementia syndromeacute myeloid leukemiamyelodysplastic syndrome
✦AI Summary

DNMT1 is the principal mammalian DNA methyltransferase responsible for maintaining DNA methylation patterns established during development 1. It preferentially methylates hemimethylated CpG residues and associates with DNA replication sites during S phase to preserve epigenetic inheritance 234. Beyond its canonical DNA methylation function, DNMT1 exhibits a dual role by binding mRNA transcripts and facilitating 5-methylcytosine RNA methylation through NSUN2 recruitment, thereby regulating genes involved in mitochondrial function 5. DNMT1 mediates transcriptional repression through direct HDAC2 binding and associates with tumor suppressor gene promoters, contributing to their silencing in cancer cells 67. During erythropoiesis, DNMT1 exerts stage-specific functions: it maintains p21 promoter methylation to regulate cell cycle progression in progenitors and maintains protein homeostasis during terminal differentiation by controlling RPL15-mediated endoplasmic reticulum stress 8. DNMT1 also regulates viral replication through DNA methylation of viral genomes, with human bocavirus NS1 protein promoting DNMT1 degradation to enhance viral RNA processing 9. Mutations in DNMT1's replication focus targeting sequence domain cause autosomal dominant cerebellar ataxia-deafness and narcolepsy through aberrant RNA methylation and mitochondrial dysfunction 5. RAD51 safeguards DNMT1 stability and function by inhibiting UHRF1-mediated degradation and facilitating DNMT1 recruitment to chr19 10.

Sources cited
1
DNMT1 methylates CpG residues and associates with DNA replication sites to maintain methylation patterns
PMID: 17200670
2
DNMT1 preferentially methylates hemimethylated DNA and maintains epigenetic inheritance during replication and across cell cycle phases
PMID: 21745816
3
DNMT1 preferentially methylates hemimethylated DNA
PMID: 26070743
4
DNMT1 is the principal DNA methyltransferase in mammalian cells with multiple regulatory features
PMID: 21507353
5
DNMT1 binds mRNA and recruits NSUN2 for RNA methylation; RFTS mutations cause neurodegeneration through mitochondrial dysfunction
PMID: 40328247
6
DNMT1 mediates transcriptional repression by direct binding to HDAC2
PMID: 10888872
7
DNMT1 associates at tumor suppressor gene promoters leading to gene silencing in cancer cells and maintains repressive state in stem cells
PMID: 24623306
8
DNMT1 regulates erythropoiesis through stage-specific mechanisms controlling cell cycle and endoplasmic reticulum stress
PMID: 38719927
9
DNMT1 regulates viral DNA methylation and replication; viral NS1 protein promotes DNMT1 degradation
PMID: 39541416
10
RAD51 safeguards DNMT1 stability by inhibiting UHRF1 ubiquitination and facilitates DNMT1 chromatin recruitment
PMID: 39621902
Disease Associationsβ“˜22
autosomal dominant cerebellar ataxia, deafness and narcolepsyOpen Targets
0.81Strong
hereditary sensory neuropathy-deafness-dementia syndromeOpen Targets
0.78Strong
acute myeloid leukemiaOpen Targets
0.62Moderate
myelodysplastic syndromeOpen Targets
0.62Moderate
cancerOpen Targets
0.61Moderate
chronic myelomonocytic leukemiaOpen Targets
0.59Moderate
refractory anemia with excess blastsOpen Targets
0.58Moderate
hereditary sensory and autonomic neuropathy type 1Open Targets
0.54Moderate
neoplasmOpen Targets
0.53Moderate
myeloid leukemiaOpen Targets
0.53Moderate
anemiaOpen Targets
0.46Moderate
deafnessOpen Targets
0.43Moderate
neurodegenerative diseaseOpen Targets
0.43Moderate
hearing loss, autosomal recessiveOpen Targets
0.43Moderate
genetic disorderOpen Targets
0.42Moderate
melanomaOpen Targets
0.40Moderate
leukemiaOpen Targets
0.40Moderate
hearing lossOpen Targets
0.38Weak
breast carcinomaOpen Targets
0.37Weak
lymphomaOpen Targets
0.35Weak
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominantUniProt
Neuropathy, hereditary sensory, 1EUniProt
Pathogenic Variants13
NM_001130823.3(DNMT1):c.1709C>T (p.Ala570Val)Pathogenic
Autosomal dominant cerebellar ataxia, deafness and narcolepsy|not provided|Hereditary sensory neuropathy-deafness-dementia syndrome|Inborn genetic diseases
β˜…β˜…β˜†β˜†2024β†’ Residue 570
NM_001130823.3(DNMT1):c.1532A>G (p.Tyr511Cys)Pathogenic
Hereditary sensory neuropathy-deafness-dementia syndrome|not provided|Charcot-Marie-Tooth disease|Autosomal dominant cerebellar ataxia, deafness and narcolepsy
β˜…β˜…β˜†β˜†2024β†’ Residue 511
NM_001130823.3(DNMT1):c.2327G>A (p.Gly776Glu)Likely pathogenic
Hereditary sensory neuropathy-deafness-dementia syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 776
NM_001130823.3(DNMT1):c.1531T>C (p.Tyr511His)Pathogenic
Hereditary sensory neuropathy-deafness-dementia syndrome|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 511
NM_001130823.3(DNMT1):c.1816G>T (p.Val606Phe)Likely pathogenic
Autosomal dominant cerebellar ataxia, deafness and narcolepsy|Hereditary sensory neuropathy-deafness-dementia syndrome|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 606
NM_001130823.3(DNMT1):c.4641G>T (p.Glu1547Asp)Likely pathogenic
Autosomal dominant cerebellar ataxia, deafness and narcolepsy
β˜…β˜†β˜†β˜†2022β†’ Residue 1547
NM_001130823.3(DNMT1):c.4490-1G>CPathogenic
Hereditary sensory neuropathy-deafness-dementia syndrome
β˜…β˜†β˜†β˜†2021
NM_001130823.3(DNMT1):c.4636C>T (p.Pro1546Ser)Likely pathogenic
Spastic ataxia
β˜…β˜†β˜†β˜†2021β†’ Residue 1546
NM_001130823.3(DNMT1):c.1619A>C (p.Tyr540Ser)Likely pathogenic
Hereditary sensory neuropathy-deafness-dementia syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 540
NM_001130823.3(DNMT1):c.1823T>G (p.Leu608Arg)Likely pathogenic
Autosomal dominant cerebellar ataxia, deafness and narcolepsy
β˜…β˜†β˜†β˜†2020β†’ Residue 608
NM_001130823.3(DNMT1):c.2858A>G (p.Asp953Gly)Likely pathogenic
Pituitary stalk interruption syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 953
NM_001130823.3(DNMT1):c.1814G>C (p.Gly605Ala)Likely pathogenic
Autosomal dominant cerebellar ataxia, deafness and narcolepsy|Hereditary sensory neuropathy-deafness-dementia syndrome
β˜…β˜†β˜†β˜†2018β†’ Residue 605
NM_001130823.3(DNMT1):c.1518_1520delinsATA (p.Asp506_Pro507delinsGluTyr)Pathogenic
Hereditary sensory neuropathy-deafness-dementia syndrome
β˜†β˜†β˜†β˜†2011β†’ Residue 506
View on ClinVar β†—
Drug Targets2
AZACITIDINEApproved
DNA (cytosine-5)-methyltransferase 1 inhibitor
refractory anemia with excess blasts
DECITABINEApproved
DNA (cytosine-5)-methyltransferase 1 inhibitor
refractory anemia with excess blasts
Related Genes
H3-5Protein interaction100%SUV39H1Protein interaction100%H3-4Protein interaction100%H3-3BProtein interaction100%H3C12Protein interaction100%H3C13Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
30%
Lung
22%
Ovary
14%
Liver
11%
Heart
10%
Gene Interaction Network
Click a node to explore
DNMT1H3-5SUV39H1H3-4H3-3BH3C12H3C13
PROTEIN STRUCTURE
Preparing viewer…
PDB6X9J Β· 1.79 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.15Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.11 [0.07–0.15]
RankingsWhere DNMT1 stands among ~20K protein-coding genes
  • #200of 20,598
    Most Researched879 Β· top 1%
  • #498of 1,025
    FDA-Approved Drug Targets2
  • #2,554of 5,498
    Most Pathogenic Variants13
  • #207of 17,882
    Most Constrained (LOEUF)0.15 Β· top 5%
Genes detectedDNMT1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
DNA methyltransferase 1 modulates mitochondrial function through bridging m
PMID: 40328247
Mol Cell Β· 2025
1.00
2
DNMT1 regulates human erythropoiesis by modulating cell cycle and endoplasmic reticulum stress in a stage-specific manner.
PMID: 38719927
Cell Death Differ Β· 2024
0.90
3
DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular cancer.
PMID: 16960727
Histochem Cell Biol Β· 2007
0.88
4
Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging.
PMID: 40009784
Gynecol Endocrinol Β· 2025
0.82
5
NS1-mediated DNMT1 degradation regulates human bocavirus 1 replication and RNA processing.
PMID: 39541416
PLoS Pathog Β· 2024
0.80