ATAD2

Chr 8

ATPase family AAA domain containing 2

Also known as: ANCCA, CT137, PRO2000

NCBI Gene: 29028 ENSG00000156802 UniProt: Q6PL18 OMIM: 611941

ATAD2 encodes a chromatin-associated ATPase with two AAA domains and a bromodomain that functions as a transcriptional coactivator, particularly for estrogen receptor signaling and cell cycle progression. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.273), but definitive disease associations in humans have not been established. Variants in this gene may potentially affect transcriptional regulation and chromatin remodeling processes.

OMIM ResearchSummary from RefSeq, UniProt

A large family of ATPases has been described, whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. The proteins that belong to this family either contain one or two AAA (ATPases Associated with diverse cellular Activities) domains. AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes. The protein encoded by this gene contains two AAA domains, as well as a bromodomain. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.27

Clinical Summary— ATAD2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

141 VUS of 183 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.998

Z-score 6.68

OE 0.17 (0.11–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.66Z-score

OE missense 0.83 (0.77–0.88)

589 obs / 713.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.11–0.27)

0≤0.351.4

Missense OE?0.83 (0.77–0.88)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 13 / 75.8Missense obs/exp: 589 / 713.7Syn Z: -0.51

This gene — mechanism propensity

0.3395th %ile

GOF

0.2298th %ile

LOF

0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

183 submitted variants in ClinVar

ClinVar

Classification Summary

VUS141

Likely Benign8

Benign1

141

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	141	0	141
Likely Benign	8	0	8
Benign	0	1	1
Total	149	1	150

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap ATAD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →