COA6

Chr 1AR

cytochrome c oxidase assembly factor 6

Also known as: C1orf31, CEMCOX4, MC4DN13

NCBI Gene: 388753ENSG00000168275UniProt: Q5JTJ3

This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 13MIM #616501
AR
128
ClinVar variants
48
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— COA6
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 35 VUS of 128 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.
1.45LOEUF
pLI 0.006
Z-score 0.81
OE 0.65 (0.32–1.45)
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.
0.72Z-score
OE missense 0.75 (0.60–0.95)
50 obs / 66.5 exp
Tolerant

Mild missense constraint

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.0.65 (0.32–1.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.60–0.95)
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.1.00
0≤1.21.6
LoF obs/exp: 4 / 6.2Missense obs/exp: 50 / 66.5Syn Z: -0.02

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic4
VUS35
Likely Benign27
Benign17
Conflicting1
44
Pathogenic
4
Likely Pathogenic
35
VUS
27
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
42
0
44
Likely Pathogenic
3
0
1
0
4
VUS
1
22
12
0
35
Likely Benign
0
1
11
15
27
Benign
0
3
14
0
17
Conflicting
—1
Total4288015128

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

View in ClinVar →

Protein Context — Lollipop Plot

COA6 · 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 13

MIM #616501

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COA6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c Oxidase.
Swaminathan AB et al.·Biomolecules
2022Review
The Key Role of COA6 in Pancreatic Ductal Adenocarcinoma: Metabolic Reprogramming and Regulation of the Immune Microenvironment.
Jiang L et al.·J Cell Mol Med
2025
Mitochondrial disease genes COA6, COX6B and SCO2 have overlapping roles in COX2 biogenesis.
Ghosh A et al.·Hum Mol Genet
2016
Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.
Abulimiti M et al.·Ann Hematol
2024
COA6 deficiency inhibits hepatocellular carcinoma progression by regulating cuproptosis through the JAK/STAT signaling pathway.
Tian K et al.·Biochim Biophys Acta Mol Cell Res
2026
Oxidative phosphorylation related gene COA6 is a novel indicator for the prognosis and immune response in lung adenocarcinoma.
Liu W et al.·Sci Rep
2024
Cuproptosis-Related Genes CDK1 and COA6 Involved in the Prognosis Prediction of Liver Hepatocellular Carcinoma.
Han S et al.·Dis Markers
2023
COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2.
Stroud DA et al.·Hum Mol Genet
2015
Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies.
Pacheu-Grau D et al.·Cell Metab
2015
Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6.
Maghool S et al.·Life Sci Alliance
2019Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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