ATAD3B
Chr 1ATPase family AAA domain containing 3B
Also known as: AAA-TOB3, TOB3
ATAD3B encodes a mitochondrial inner membrane protein that negatively regulates ATAD3A's interaction with matrix nucleoid complexes and may organize mitochondrial networks in stem cells by reducing mitochondrial metabolism and fragmenting the mitochondrial network. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. The gene shows tolerance to loss-of-function variants in the general population (LOEUF 1.477), suggesting pathogenic variants may require specific functional consequences rather than simple protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
427 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 131 | 0 | 131 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 1 | 185 | 34 | 0 | 220 |
Likely Benign | 0 | 14 | 3 | 3 | 20 |
Benign | 0 | 3 | 6 | 1 | 10 |
Conflicting | — | 3 | |||
| Total | 1 | 202 | 183 | 4 | 393 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATAD3B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools