DNMT1

Chr 19AD

DNA methyltransferase 1

Also known as: ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT, m.HsaI

NCBI Gene: 1786ENSG00000130816UniProt: P26358

This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Cerebellar ataxia, deafness, and narcolepsy, autosomal dominantMIM #604121
AD
Neuropathy, hereditary sensory, type IEMIM #614116
AD
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
9
Active trials
Clinical Summary— DNMT1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.14LOEUF
pLI 1.000
Z-score 8.21
OE 0.08 (0.04–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.99Z-score
OE missense 0.55 (0.51–0.59)
537 obs / 975.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.51–0.59)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 7 / 91.9Missense obs/exp: 537 / 975.6Syn Z: -0.36

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DNMT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant

MIM #604121

Molecular basis of disorder known

Autosomal dominant

Neuropathy, hereditary sensory, type IE

MIM #614116

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Glioblastoma

A Study Using Radiation Therapy and Temozolomide to Treat Glioblastoma in Patients Over 70

ACTIVE NOT RECRUITING
NCT01985087Phase PHASE1, PHASE2University of LouisvilleStarted 2014-09
Hypofractionated radiotherapyTemozolomide
NeoplasmsSolid Tumors

5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in People With Advanced Solid Tumors

RECRUITING
NCT03366116Phase PHASE1National Cancer Institute (NCI)Started 2018-11-05
aza-TdC
Overweight and ObesityLupus Erythematosus

Methyl-donor Nutrient Supplementation and Methylation Profile in Lupus Patients With Obesity

ENROLLING BY INVITATION
NCT05097365Phase NAUniversity of Sao PauloStarted 2022-01-01
Vitamin B12 + folic acid supplementationPlacebo supplementation
Peripheral T Cells Lymphoma (PTCL)

Zeprumetostat, Azacitidine Combined With Lipo-MIT in R/R PTCL

RECRUITING
NCT07372352Phase PHASE2The First Affiliated Hospital of Soochow UniversityStarted 2026-01-15
ZeprumetostatAzacitidine (AZA)Mitoxantrone Hydrochloride Liposome
Glioblastoma, IDH-wildtypeMGMT-Methylated Glioblastoma

Lomustine in Addition to Standard of Care in Patients With MGMT Methylated Glioblastoma

NOT YET RECRUITING
NCT06419946Phase PHASE3Vastra Gotaland RegionStarted 2024-12-01
TemozolomideLomustine
BRCA1 MutationBRCA2 MutationBRCA Mutation

Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors

RECRUITING
NCT06177171Phase PHASE1Pamela MunsterStarted 2024-02-07
OlaparibASTX727
Glioma

Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

RECRUITING
NCT07077616Phase EARLY_PHASE1Biogenea Pharmaceuticals Ltd.Started 2025-07-01
Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;
Polycystic Ovary Syndrome

Ovary Syndrome for Efficient Diagnosis and Targeted Therapy

NOT YET RECRUITING
NCT06102629Phase NAAsian Institute of Gastroenterology, IndiaStarted 2023-11-05
laparoscopy / laparotomyNO INTERVENTION
MesotheliomaMalignant Mesothelioma (MM)Early-stage Mesothelioma

Alrizomadlin (APG-115) in Subjects With BAP1 Cancer Syndrome and Early-Stage Mesothelioma

NOT YET RECRUITING
NCT06654050Phase PHASE2National Cancer Institute (NCI)Started 2026-03-12
alrizomadlin

External Resources

Links to major genomics databases and tools