COX6B1

Chr 19AR

cytochrome c oxidase subunit 6B1

Also known as: COX6B, COXG, COXVIb1, MC4DN7

NCBI Gene: 1340ENSG00000126267UniProt: P14854OMIM: 124089

The COX6B1 protein is a nuclear-encoded structural subunit of cytochrome c oxidase (complex IV) that regulates assembly of this terminal mitochondrial respiratory chain enzyme responsible for electron transfer from cytochrome c to oxygen. Mutations cause mitochondrial complex IV deficiency nuclear type 7, presenting as severe infantile encephalomyopathy with autosomal recessive inheritance. The pathogenic mechanism involves impaired complex IV assembly leading to defective mitochondrial respiration.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.171 OMIM phenotype
Clinical Summary— COX6B1
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 29 VUS of 90 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 0.121
Z-score 1.34
OE 0.37 (0.15–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.75Z-score
OE missense 0.72 (0.56–0.94)
40 obs / 55.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.15–1.17)
0≤0.351.4
Missense OE0.72 (0.56–0.94)
0≤0.61.4
Synonymous OE0.79
0≤1.21.6
LoF obs/exp: 2 / 5.4Missense obs/exp: 40 / 55.7Syn Z: 0.76
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOX6B1-related mitochondrial complex IV deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6453th %ile
GOF
0.6249th %ile
LOF
0.2483th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS29
Likely Benign27
Benign6
Conflicting5
14
Pathogenic
2
Likely Pathogenic
29
VUS
27
Likely Benign
6
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
2
0
0
2
VUS
0
20
9
0
29
Likely Benign
0
0
18
9
27
Benign
0
0
5
1
6
Conflicting
—5
Total022461083

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

View in ClinVar →

Protein Context — Lollipop Plot

COX6B1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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
Identification of potential biomarkers associated with mitochondrial oxidative stress in idiopathic pulmonary arterial hypertension via bioinformatic and experimental analysis
Zhu Y et al.·Sci Rep
2025
Genetic Evidence Prioritizes Neurocognitive Decline as a Causal Driver of Sleep Disturbances: A Multi-Omics Analysis Identifying Causal Genes and Therapeutic Targets
Du Y et al.·Curr Issues Mol Biol
2025
Gene crosstalk between COVID-19 and preeclampsia revealed by blood transcriptome analysis
Chu Y et al.·Front Immunol
2024
Phosphorylation regulation of cardiac proteins in Babesia microti infected mice in an effort to restore heart function
Yang X et al.·Parasit Vectors
2022
Integrated analysis of ATAC-seq and RNA-seq reveals ADSCP2 regulates oxidative phosphorylation pathway in hypertrophic scar fibroblasts
Li Q et al.·PeerJ
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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