DMAP1

Chr 1

DNA methyltransferase 1 associated protein 1

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

NCBI Gene: 55929 ENSG00000178028 UniProt: Q9NPF5 OMIM: 605077

The protein functions as a transcriptional regulator that both represses and activates gene expression through interactions with histone-modifying complexes, including histone deacetylases and the NuA4 histone acetyltransferase complex. DMAP1 mutations cause autosomal recessive intellectual disability with variable additional features including microcephaly and seizures. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— DMAP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 59 VUS of 75 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.29 (0.17–0.55)

0≤0.351.4

Missense OE?0.63 (0.55–0.71)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 7 / 24.0Missense obs/exp: 186 / 297.3Syn Z: -0.05

This gene — mechanism propensity

0.6552th %ile

GOF

0.4776th %ile

LOF

0.52top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS59

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	2	56	1	59
Likely Benign	0	0	0	0
Benign	0	0	0	0
Total	3	56	1	60

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap DMAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →