DMAP1

Chr 1AR

DNA methyltransferase 1 associated protein 1

Also known as: DNMAP1, DNMTAP1, EAF2, MEAF2, MRT86, 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…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 86MIM #621738

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intellectual developmental disorder, autosomal recessive 86; no ClinGen or GenCC tier

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.55

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in DMAP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

491 rare PASS variants

Rare truncating (LoF)

1 in 2,300

68 rare PASS variants

Rare synonymous (reference)

1 in 75

248 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DMAP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,900
South Asian	~43k	1 in 210	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 110	1 in 2,500
European (Finnish)	~27k	1 in 230	≈ 1 in 27,000
Admixed American	~22k	1 in 120	≈ 1 in 7,600
African / African American	~21k	1 in 150	≈ 1 in 9,300
East Asian	~20k	1 in 310	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 720	none seen
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓