DNMT1

Chr 19AD

DNA methyltransferase 1

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

NCBI Gene: 1786 ENSG00000130816 UniProt: P26358 OMIM: 126375

This gene encodes DNA methyltransferase 1, the primary enzyme responsible for maintaining DNA methylation patterns during replication, which is essential for epigenetic gene regulation. Mutations cause autosomal dominant cerebellar ataxia with deafness and narcolepsy, and hereditary sensory neuropathy type IE. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0), reflecting its critical role in cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cerebellar ataxia, deafness, and narcolepsy, autosomal dominantMIM #604121

Neuropathy, hereditary sensory, type IEMIM #614116

Clinical highlights

Gene-disease validity (ClinGen)

autosomal dominant cerebellar ataxia, deafness and narcolepsy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — DNMT1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.08 (0.04–0.14)

0≤0.351.4

Missense OE?0.55 (0.51–0.59)

0≤0.61.4

Synonymous OE?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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — DNMT1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Glioblastoma, IDH-wildtypeMGMT-Methylated Glioblastoma

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

RECRUITING

NCT06419946Phase PHASE3Vastra Gotaland RegionStarted 2025-02-01

TemozolomideLomustine

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

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

BRCA1 MutationBRCA2 MutationBRCA Mutation

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

RECRUITING

NCT06177171Phase PHASE1Varun Monga, MBBSStarted 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;

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