COX16

Chr 14AR

cytochrome c oxidase assembly factor COX16

Also known as: C14orf112, HSPC203, MC4DN22, hCOX16

NCBI Gene: 51241ENSG00000133983UniProt: Q9P0S2

Involved in mitochondrial cytochrome c oxidase assembly. Located in mitochondrial inner membrane. Implicated in mitochondrial complex IV deficiency nuclear type 22. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 22MIM #619355
AR
28
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COX16
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 15 VUS of 28 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.
1.78LOEUF
pLI 0.000
Z-score -0.10
OE 1.04 (0.58–1.78)
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.
0.25Z-score
OE missense 0.90 (0.71–1.15)
48 obs / 53.2 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.1.04 (0.58–1.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.71–1.15)
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.1.14
0≤1.21.6
LoF obs/exp: 7 / 6.7Missense obs/exp: 48 / 53.2Syn Z: -0.46

ClinVar Variant Classifications

28 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS15
Likely Benign3
8
Pathogenic
2
Likely Pathogenic
15
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
13
2
0
15
Likely Benign
0
0
0
3
3
Benign
0
0
0
0
0
Total01312328

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

View in ClinVar →

Protein Context — Lollipop Plot

COX16 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COX16-related developmental disorder

strong
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 22

MIM #619355

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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