COA3

Chr 17AR

cytochrome c oxidase assembly factor 3

Also known as: CCDC56, COX25, HSPC009, MC4DN14, MITRAC12, hCOA3

NCBI Gene: 28958ENSG00000183978UniProt: Q9Y2R0

This gene encodes a member of the cytochrome c oxidase assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for cytochrome c oxidase function. [provided by RefSeq, Nov 2012]

Primary Disease Associations & Inheritance

?Mitochondrial complex IV deficiency, nuclear type 14MIM #619058
AR
0
Active trials
50
ClinVar variants
6
Pathogenic / LP
-0.2
Missense Z
1.53
LOEUF
6
Pubs (2 yr)
Clinical Summary— COA3
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 34 VUS of 50 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.53LOEUF
pLI 0.065
Z-score 0.87
OE 0.52 (0.21–1.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.19Z-score
OE missense 1.07 (0.88–1.30)
71 obs / 66.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.21–1.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.88–1.30)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.66
0≤1.21.6
LoF obs/exp: 2 / 3.8Missense obs/exp: 71 / 66.7Syn Z: 1.47

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS34
Likely Benign10
6
Pathogenic
34
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
2
29
3
0
34
Likely Benign
0
1
3
6
10
Benign
0
0
0
0
0
Total23012650

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

View in ClinVar →

Protein Context — Lollipop Plot

COA3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Mitochondrial complex IV deficiency, nuclear type 14

MIM #619058

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver.
Aich A et al.·Nat Commun
2024Functional
Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature.
Ostergaard E et al.·J Med Genet
2015Case report
Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy.
Dong HL et al.·Brain
2021
Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients.
Fritsch H et al.·Genes (Basel)
2024Cohort
N6-methyladenosine methylation regulatory pattern of pulmonary lymphoepithelioma-like carcinoma based on exosomal transcriptome analysis.
Yu M et al.·Mol Carcinog
2023
EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming.
Meng F et al.·Nat Commun
2019
Molecular characterization of human HSPCs with different cell fates in vivo using single-cell transcriptome analysis and lentiviral barcoding technology.
Hua J et al.·Clin Transl Med
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The Cyclic Oligoadenylate Signaling Pathway of Type III CRISPR-Cas Systems
Huang F et al.·Front Microbiol
2021
Genetic prediction of the relationship between mitochondrial proteins and diabetic polyneuropathy risk: a Mendelian randomization study.
Wang Z et al.·Endocr Res
2025
Integrated transcriptomic and network analysis reveals candidate immune-metabolic biomarkers in children with the inattentive type of ADHD.
Shao Q et al.·Front Psychiatry
2025
Assessing causality between mitochondrial-associated proteins with musculoskeletal diseases: A Mendelian randomization study
Li JC et al.·Medicine (Baltimore)
2025
Integrative genomics analysis highlights functionally relevant genes for equine behaviour.
Holtby AR et al.·Anim Genet
2023Functional
Comparative Proteomics of Rat Olfactory Bulb Reveal Insights into Susceptibility and Resiliency to Chronic-stress-induced Depression or Anxiety.
Liu D et al.·Neuroscience
2021
Top 6 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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