TADA2A

Chr 17

transcriptional adaptor 2A

Also known as: ADA2, ADA2A, KL04P, TADA2L, hADA2

NCBI Gene: 6871 ENSG00000276234 UniProt: O75478 OMIM: 602276

The TADA2A protein is a component of the ATAC histone acetyltransferase complex that acetylates histones H3 and H4, binds double-stranded DNA, and plays a role in chromatin remodeling and transcriptional activation. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly intolerant to loss-of-function variants. This condition primarily affects neurodevelopment and cognitive function.

OMIM ResearchSummary from RefSeq, UniProt

Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated gene transcription by interacting functionally with the general transcription machinery bound at the basal promoter. Adaptor proteins are usually required for this activation, possibly to acetylate and destabilize nucleosomes, thereby relieving chromatin constraints at the promoter. The protein encoded by this gene is a transcriptional activator adaptor and has been found to be part of the PCAF histone acetylase complex. Several alternatively spliced transcript variants encoding different isoforms of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in TADA2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

518 rare PASS variants

Rare truncating (LoF)

1 in 1,800

103 rare PASS variants

Rare synonymous (reference)

1 in 340

212 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TADA2A. 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 210	1 in 2,200
South Asian	~43k	1 in 120	1 in 1,300
Remaining (unassigned)	~30k	1 in 110	1 in 2,200
European (Finnish)	~27k	1 in 530	1 in 4,400
Admixed American	~22k	1 in 110	1 in 1,200
African / African American	~21k	1 in 120	1 in 1,500
East Asian	~20k	1 in 160	1 in 2,800
Ashkenazi Jewish	~13k	1 in 930	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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): 14 of 15 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 15.? see exons ↓