ATAD3A: ATPase Family AAA Domain Containing 3A
A mitochondrial AAA-ATPase implicated in mitochondrial dynamics, cholesterol metabolism, and hereditary neurological disorders.
Gene Information Card
| Symbol | ATAD3A |
|---|---|
| Full Name | ATPase family AAA domain containing 3A |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 55210 ncbi.nlm.nih.gov/gene/55210 |
| Ensembl ID | ENSG00000197785 |
| UniProt ID | Q9NVI7 |
| OMIM ID | 612316 |
| HGNC ID | 25567 |
| Aliases | ATAD3, MGC2498 |
Description
ATAD3A encodes a mitochondrial inner membrane AAA-ATPase that is essential for mitochondrial dynamics, nucleoid organization, and cholesterol metabolism. It is involved in the maintenance of mitochondrial DNA and protein synthesis. Mutations in ATAD3A are associated with autosomal dominant and recessive neurological disorders, including Harel-Yoon syndrome, characterized by developmental delay, hypotonia, optic atrophy, and cardiomyopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Harel-Yoon syndrome | Dominant-negative or loss-of-function mutations impair mitochondrial ATPase activity, leading to mitochondrial dysfunction and neurodegeneration. | OMIM #617183; ClinVar |
| Optic atrophy 10 | Missense mutations disrupt mitochondrial dynamics and axonal integrity, causing optic nerve degeneration. | OMIM #616732; ClinVar |
| Mitochondrial DNA depletion syndrome | ATAD3A mutations reduce mitochondrial DNA copy number, leading to energy deficiency in affected tissues. | PubMed; ClinVar |
| Cardiomyopathy | Altered ATAD3A function affects mitochondrial cholesterol metabolism and ATP production, contributing to cardiac dysfunction. | OMIM; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | High |
| Heart | 10.1 | High |
| Liver | 8.5 | Medium |
| Skeletal Muscle | 7.2 | Medium |
| Kidney | 6.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| HepG2 | 12.8 | Liver cancer cell line |
| SH-SY5Y | 18.4 | Neuroblastoma cell line |
| MCF7 | 9.7 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg239Trp | Missense | Rare | Dominant-negative effect; reduces ATPase activity and disrupts mitochondrial dynamics. |
| p.Arg239Gln | Missense | Rare | Similar to Arg239Trp; associated with Harel-Yoon syndrome. |
| p.Ala249Val | Missense | Rare | Loss-of-function; impairs mitochondrial DNA maintenance. |
| c.1062+1G>A | Splice site | Rare | Splicing defect leading to truncated protein; loss-of-function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., splice site) reduce ATAD3A protein levels or ATPase activity, impairing mitochondrial function and causing recessive phenotypes.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some missense mutations may exert dominant-negative effects rather than gain-of-function.
Dominant Negative (DN)
Missense mutations like p.Arg239Trp act in a dominant-negative manner, interfering with the function of the wild-type allele in oligomeric complexes.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis activity | • Mitochondrial inner membrane |
| • Mitochondrial nucleoid | • Cholesterol binding |
| • Protein homodimerization activity | • Mitochondrial DNA replication |
Pathways
• Mitochondrial dynamics
• Cholesterol metabolism
• Mitochondrial DNA maintenance
Protein Summary
ATAD3A is a 586-amino acid protein localized to the mitochondrial inner membrane. It contains an AAA-ATPase domain that hydrolyzes ATP to drive conformational changes. The protein forms homo-oligomers and interacts with mitochondrial DNA and proteins involved in cholesterol transport. It plays a critical role in mitochondrial nucleoid organization, mitochondrial fission/fusion, and steroidogenesis. Defects in ATAD3A lead to mitochondrial dysfunction and are linked to several neurological and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATAD3A Knockout HEK293 Cell Line | EDJ-KQ11743 | Human | 55210 | Details Get a Quote |
| ATAD3A Knockout A-549 Cell Line | EDJ-KQ41401 | Human | 55210 | Details Get a Quote |
| ATAD3A Knockout HCT 116 Cell Line | EDJ-KQ41402 | Human | 55210 | Details Get a Quote |
| ATAD3A Knockout HeLa Cell Line | EDJ-KQ41403 | Human | 55210 | Details Get a Quote |
