TADA2A

Chr 17

transcriptional adaptor 2A

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

NCBI Gene: 6871 ENSG00000276234 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…

LOEUF 0.85

Clinical Summary— TADA2A

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

54 VUS of 73 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.23

OE 0.57 (0.39–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.46Z-score

OE missense 0.74 (0.66–0.84)

186 obs / 251.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.39–0.85)

0≤0.351.4

Missense OE?0.74 (0.66–0.84)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 18 / 31.5Missense obs/exp: 186 / 251.3Syn Z: -1.04

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	54	54
Likely Benign	0	0
Benign	0	0
Total	54	54

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

View in ClinVar →

136 pathogenic / likely-pathogenic (of 150) ClinVar copy-number / structural variants overlap TADA2A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →