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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ATAD3C
ATPase family AAA domain containing 3C
Chromosome 1 · 1p36.33
NCBI Gene: 219293Ensembl: ENSG00000215915.10HGNC: HGNC:32151UniProt: Q5T2N8
34PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrion organizationmitochondrionATP bindingATP hydrolysis activityneurodegenerative diseaseulcerative proctosigmoiditishypertriglyceridemia 2familial hypercholesterolemia
✦AI Summary

ATAD3C is a mitochondrial integral membrane protein and paralog of ATAD3A that arose through gene duplication in primates 1. Although previously considered a pseudogene, ATAD3C is genuinely expressed in human tissues with expression levels similar to ATAD3A 2. ATAD3C functions as a negative regulator of ATAD3A assembly and mitochondrial function. Overexpression of ATAD3C reduces cell proliferation and oxygen consumption while increasing reactive oxygen species production by incorporating into ATAD3A protein complexes and reducing their size 2. This disrupts respiratory chain organization, promoting accumulation of respiratory complex III dimers at the expense of supercomplex assembly 2. ATAD3C is clinically relevant through its involvement in dominant-negative pathological variants. De novo duplications at the ATAD3 locus produce chimeric ATAD3A/ATAD3C fusion proteins causing lethal perinatal cardiomyopathy, hyperlactacidemia, encephalopathy, and corneal clouding 34. These duplications dramatically reduce mitochondrial oxidative phosphorylation complex I activity in cardiac tissue 3. ATAD3 locus duplications now rank among the five most common causes of nuclear-encoded pediatric mitochondrial disease, though diagnosis is frequently missed due to the repetitive nature of this genomic region 3.

Sources cited
1
ATAD3C is an expressed integral membrane protein that negatively regulates ATAD3A complex assembly and mitochondrial function
PMID: 38092275
2
ATAD3 duplications create chimeric ATAD3A/ATAD3C proteins causing lethal perinatal cardiomyopathy and reduced complex I activity
PMID: 33575671
3
ATAD3 duplications produce fusion proteins acting through dominant-negative mechanism in hereditary mitochondrial disease
PMID: 32004445
4
ATAD3C is a paralog gene that arose in primates alongside ATAD3B from ancestral ATAD3A
PMID: 22318359
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.24Weak
ulcerative proctosigmoiditisOpen Targets
0.06Suggestive
hypertriglyceridemia 2Open Targets
0.05Suggestive
familial hypercholesterolemiaOpen Targets
0.05Suggestive
pancreatic triacylglycerol lipase deficiencyOpen Targets
0.05Suggestive
Combined hyperlipidemiaOpen Targets
0.04Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.04Suggestive
sitosterolemia 2Open Targets
0.04Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.04Suggestive
hypercholesterolemia, autosomal dominant, 3Open Targets
0.03Suggestive
hyperlipidemia due to hepatic triglyceride lipase deficiencyOpen Targets
0.03Suggestive
hypercholesterolemia, autosomal dominant, type BOpen Targets
0.03Suggestive
chylomicron retention diseaseOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
inflammatory bowel diseaseOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.01Suggestive
nervous system diseaseOpen Targets
0.00Suggestive
mitochondrial diseaseOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GABPB1Shared pathway100%PYROXD2Shared pathway100%ATAD3BShared pathway72%NIPSNAP2Shared pathway50%AFG1LShared pathway50%TMEM11Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Brain
33%
Lung
32%
Ovary
32%
Heart
7%
Bone Marrow
5%
Gene Interaction Network
Click a node to explore
ATAD3CGABPB1PYROXD2ATAD3BNIPSNAP2AFG1LTMEM11
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5T2N8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.68–1.15]
RankingsWhere ATAD3C stands among ~20K protein-coding genes
  • #11,115of 20,598
    Most Researched34
  • #11,983of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedATAD3C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Recurrent De Novo and Biallelic Variation of ATAD3A, Encoding a Mitochondrial Membrane Protein, Results in Distinct Neurological Syndromes.
PMID: 27640307
Am J Hum Genet · 2016
1.00
2
Fatal perinatal mitochondrial cardiac failure caused by recurrent
PMID: 33575671
Med · 2021
0.90
3
"ATAD3C regulates ATAD3A assembly and function in the mitochondrial membrane".
PMID: 38092275
Free Radic Biol Med · 2024
0.80
4
Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.
PMID: 32004445
Am J Hum Genet · 2020
0.70
5
Associations between antenatal maternal asthma status and placental DNA methylation.
PMID: 35858526
Placenta · 2022
0.60