ATAD3C

Chr 1

ATPase family AAA domain containing 3C

NCBI Gene: 219293ENSG00000215915UniProt: Q5T2N8

The ATAD3C protein is an ATPase that hydrolyzes ATP and is involved in mitochondrial organization. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy. This gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are unaffected.

Summary from RefSeq
Research Assistant →
0
Active trials
0
Pubs (1 yr)
138
P/LP submissions
0%
P/LP missense
1.17
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ATAD3C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
131 unique Pathogenic / Likely Pathogenic· 138 VUS of 307 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 0.98
OE 0.76 (0.51–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.82Z-score
OE missense 1.14 (1.04–1.25)
302 obs / 264.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.76 (0.51–1.17)
0≤0.351.4
Missense OE1.14 (1.04–1.25)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 15 / 19.7Missense obs/exp: 302 / 264.7Syn Z: -1.40
DN
0.79top 25%
GOF
0.6443th %ile
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

307 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic124
Likely Pathogenic7
VUS138
Likely Benign14
Benign4
Conflicting2
124
Pathogenic
7
Likely Pathogenic
138
VUS
14
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
124
0
124
Likely Pathogenic
0
0
7
0
7
VUS
0
110
28
0
138
Likely Benign
0
9
4
1
14
Benign
0
1
3
0
4
Conflicting
—2
Total01201661289

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

View in ClinVar →

Protein Context — Lollipop Plot

ATAD3C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients