DRAP1

Chr 11

DR1 associated protein 1

Also known as: NC2-alpha

NCBI Gene: 10589 ENSG00000175550 UniProt: Q14919

DRAP1 encodes a transcriptional corepressor that forms a heterodimer with DR1 to inhibit RNA polymerase II transcription by preventing TFIIA and TFIIB from associating with the TATA-binding protein. Mutations in DRAP1 cause autosomal recessive developmental delay with seizures and intellectual disability, typically presenting in infancy with early-onset seizures and severe developmental impairment. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.795), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Transcriptional repression is a general mechanism for regulating transcriptional initiation in organisms ranging from yeast to humans. Accurate initiation of transcription from eukaryotic protein-encoding genes requires the assembly of a large multiprotein complex consisting of RNA polymerase II and general transcription factors such as TFIIA, TFIIB, and TFIID. DR1 is a repressor that interacts with the TATA-binding protein (TBP) of TFIID and prevents the formation of an active transcription complex by precluding the entry of TFIIA and/or TFIIB into the preinitiation complex. The protein encoded by this gene is a corepressor of transcription that interacts with DR1 to enhance DR1-mediated repression. The interaction between this corepressor and DR1 is required for corepressor function and appears to stabilize the TBP-DR1-DNA complex. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

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

0.80

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.130

Z-score 2.00

OE 0.31 (0.14–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.87Z-score

OE missense 0.78 (0.66–0.92)

94 obs / 120.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.14–0.80)

0≤0.351.4

Missense OE?0.78 (0.66–0.92)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 3 / 9.8Missense obs/exp: 94 / 120.8Syn Z: -1.67

Background carrier burden — how many people carry a rare variant somewhere in DRAP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

281 rare PASS variants

Rare truncating (LoF)

1 in 8,500

35 rare PASS variants

Rare synonymous (reference)

1 in 220

130 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DRAP1. 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 370	1 in 480
South Asian	~43k	1 in 380	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 290	≈ 1 in 15,000
European (Finnish)	~27k	1 in 720	1 in 630
Admixed American	~22k	1 in 390	1 in 1,400
African / African American	~21k	1 in 210	1 in 2,500
East Asian	~20k	1 in 160	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 930	1 in 1,400
Middle Eastern	~2,884	1 in 560	≈ 1 in 2,900

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓