ATAD3B

Chr 1

ATPase family AAA domain containing 3B

Also known as: AAA-TOB3, TOB3

NCBI Gene: 83858 ENSG00000160072 UniProt: Q5T9A4

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is localized to the mitochondrial inner membrane, where it can bind to a highly-related protein, ATAD3A. ATAD3A appears to interact with matrix nucleoid complexes, and the encoded protein negatively regulates that interaction. This gene is expressed almost exclusively in pluripotent embryonic stem cells and some cancer cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.48

Clinical Summary— ATAD3B

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Population Constraint (gnomAD)

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

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 193 VUS of 258 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.48LOEUF

pLI 0.000

Z-score -0.50

OE 1.10 (0.83–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.79Z-score

OE missense 1.39 (1.30–1.49)

557 obs / 399.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.10 (0.83–1.48)

0≤0.351.4

Missense OE?1.39 (1.30–1.49)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 32 / 29.1Missense obs/exp: 557 / 399.9Syn Z: -3.46

This gene — mechanism propensity

0.74top 25%

GOF

0.76top 25%

LOF

0.3357th %ile

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.

GOFprediction above median

DNprediction above median

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

258 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

VUS193

Likely Benign18

Benign6

Conflicting2

Pathogenic

193

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	6	0	6
Likely Pathogenic	0	0	0	0	0
VUS	2	187	4	0	193
Likely Benign	0	14	1	3	18
Benign	0	3	2	1	6
Conflicting	—				2
Total	2	204	13	4	225

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

View in ClinVar →

137 pathogenic / likely-pathogenic (of 174) ClinVar copy-number / structural variants overlap ATAD3B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →