TADA2B

Chr 4

transcriptional adaptor 2B

Also known as: ADA2(beta), ADA2B

NCBI Gene: 93624 ENSG00000173011 UniProt: Q86TJ2 OMIM: 608790

TADA2B encodes a transcriptional adaptor protein that coordinates histone acetyltransferase activity and links transcription factors to basal transcriptional machinery. Mutations cause intellectual disability with speech delay and dysmorphic facies, inherited in an autosomal dominant pattern. The gene shows high constraint against loss-of-function variants, suggesting intolerance to haploinsufficiency.

OMIM ResearchSummary from RefSeq, UniProt

TADA2B functions as a transcriptional adaptor protein that potentiates transcription through coordination of histone acetyltransferase (HAT) activity and by linking activation factors to basal transcriptional machinery (Barlev et al., 2003 [PubMed 12972612]).[supplied by OMIM, Apr 2010]

OMIM 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

0.49

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.724

Z-score 2.82

OE 0.15 (0.06–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.80Z-score

OE missense 0.52 (0.45–0.59)

136 obs / 263.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.06–0.49)

0≤0.351.4

Missense OE?0.52 (0.45–0.59)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 2 / 12.9Missense obs/exp: 136 / 263.8Syn Z: -0.39

Background carrier burden — how many people carry a rare variant somewhere in TADA2B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

468 rare PASS variants

Rare truncating (LoF)

1 in 7,900

33 rare PASS variants

Rare synonymous (reference)

1 in 220

258 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TADA2B. 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 5,600
South Asian	~43k	1 in 250	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 240	≈ 1 in 30,000
European (Finnish)	~27k	1 in 890	≈ 1 in 7,500
Admixed American	~22k	1 in 260	none seen
African / African American	~21k	1 in 300	≈ 1 in 4,200
East Asian	~20k	1 in 280	≈ 1 in 9,800
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 200	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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓