COX6B1

Chr 19AR

cytochrome c oxidase subunit 6B1

Also known as: COX6B, COXG, COXVIb1, MC4DN7

NCBI Gene: 1340ENSG00000126267UniProt: P14854

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIb. Mutations in this gene are associated with severe infantile encephalomyopathy. Three pseudogenes COX6BP-1, COX6BP-2 and COX6BP-3 have been found on chromosomes 7, 17 and 22q13.1-13.2, respectively. [provided by RefSeq, Jan 2010]

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 7MIM #619051
AR
83
ClinVar variants
16
Pathogenic / LP
0.12
pLI score
0
Active trials
Clinical Summary— COX6B1
🧬
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.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 29 VUS of 83 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.
1.17LOEUF
pLI 0.121
Z-score 1.34
OE 0.37 (0.15–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?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.
0.75Z-score
OE missense 0.72 (0.56–0.94)
40 obs / 55.7 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.0.37 (0.15–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.56–0.94)
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.0.79
0≤1.21.6
LoF obs/exp: 2 / 5.4Missense obs/exp: 40 / 55.7Syn Z: 0.76

ClinVar Variant Classifications

83 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.

Gene2Phenotype Curations

COX6B1-related mitochondrial complex IV deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex IV deficiency, nuclear type 7

MIM #619051

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel homozygous pathogenic missense variant in COX6B1: Further delineation of the phenotype.
Jennions E et al.·Am J Med Genet A
2024Case report
Proteomic Analysis Reveals Oxidative Phosphorylation and JAK-STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris.
Cheng Y et al.·Exp Dermatol
2024
[miR-30b-3p Inhibits the Proliferation and Invasion of Lung Adenocarcinoma 
by Targeting COX6B1].
Chen L et al.·Zhongguo Fei Ai Za Zhi
2022
The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.
Čunátová K et al.·J Biol Chem
2026
The pathomechanism of cytochrome c oxidase deficiency includes nuclear DNA damage.
Douiev L et al.·Biochim Biophys Acta Bioenerg
2018Functional
Integrative analysis of metabolism subtypes and identification of prognostic metabolism-related genes for glioblastoma.
Li J et al.·Biosci Rep
2024
Construction of oxidative phosphorylation-related prognostic risk score model in uveal melanoma.
Zhan Z et al.·BMC Ophthalmol
2024Functional
Cytochrome c oxidase deficiency, oxidative stress, possible antioxidant therapy and link to nuclear DNA damage.
Douiev L et al.·Eur J Hum Genet
2018
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