DMAP1

Chr 1

DNA methyltransferase 1 associated protein 1

Also known as: DNMAP1, DNMTAP1, EAF2, MEAF2, SWC4

NCBI Gene: 55929ENSG00000178028UniProt: Q9NPF5

This gene encodes a subunit of several, distinct complexes involved in the repression or activation of transcription. The encoded protein can independently repress transcription and is targeted to replication foci throughout S phase by interacting directly with the N-terminus of DNA methyltransferase 1. During late S phase, histone deacetylase 2 is added to this complex, providing a means to deacetylate histones in transcriptionally inactive heterochromatin following replication. The encoded protein is also a component of the nucleosome acetyltransferase of H4 complex and interacts with the transcriptional corepressor tumor susceptibility gene 101 and the pro-apoptotic death-associated protein 6, among others. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

75
ClinVar variants
10
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— DMAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 65 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.55LOEUF
pLI 0.041
Z-score 3.22
OE 0.29 (0.17–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.29Z-score
OE missense 0.63 (0.55–0.71)
186 obs / 297.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.29 (0.17–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.55–0.71)
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.1.01
0≤1.21.6
LoF obs/exp: 7 / 24.0Missense obs/exp: 186 / 297.3Syn Z: -0.05

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS65
8
Pathogenic
2
Likely Pathogenic
65
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
1
0
1
0
2
VUS
1
56
8
0
65
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total25617075

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DMAP1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
Monies D et al.·Hum Genet
2017
De novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.
Ha T et al.·Am J Med Genet A
2024
Inherited mutations affecting the SRCAP complex are central in moderate-penetrance predisposition to uterine leiomyomas.
Välimäki N et al.·Am J Hum Genet
2023
LOXL2-mediated chromatin compaction is required to maintain the oncogenic properties of triple-negative breast cancer cells.
Serra-Bardenys G et al.·FEBS J
2024
MDGA2 is a novel tumour suppressor cooperating with DMAP1 in gastric cancer and is associated with disease outcome.
Wang K et al.·Gut
2016
Epigenome-wide methylation differences in a group of lean and obese women - A HUNT Study.
Kvaløy K et al.·Sci Rep
2018
DNA methyltransferase 1-associated protein (DMAP1) is a co-repressor that stimulates DNA methylation globally and locally at sites of double strand break repair.
Lee GE et al.·J Biol Chem
2010
Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma.
Nie E et al.·Oncogene
2019
Ad E1A 243R oncoprotein promotes association of proto-oncogene product MYC with the NuA4/Tip60 complex via the E1A N-terminal repression domain.
Zhao LJ et al.·Virology
2016
Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans.
Doyon Y et al.·Mol Cell Biol
2004Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The DNA methyltransferase DMAP1 is required for tissue maintenance and planarian regeneration.
Rojas S et al.·Dev Biol
2024
Identification, characterization, and CADD analysis of Plasmodium DMAP1 reveals it as a potential molecular target for new anti-malarial discovery.
Lawrence M et al.·J Biomol Struct Dyn
2025
Comprehensive Combined Proteomics and Genomics Analysis Identifies Prognostic Related Transcription Factors in Breast Cancer and Explores the Role of DMAP1 in Breast Cancer.
Li X et al.·J Pers Med
2021🔓 Open Access
MMTR/Dmap1 Sets the Stage for Early Lineage Commitment of Embryonic Stem Cells by Crosstalk with PcG Proteins.
Lee YJ et al.·Cells
2020🔓 Open Access
ARID1A Regulates Transcription and the Epigenetic Landscape via POLE and DMAP1 while ARID1A Deficiency or Pharmacological Inhibition Sensitizes Germ Cell Tumor Cells to ATR Inhibition.
Kurz L et al.·Cancers (Basel)
2020🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools