COX16

Chr 14AR

cytochrome c oxidase assembly factor COX16

Also known as: C14orf112, HSPC203, MC4DN22, hCOX16

COX16 encodes a protein required for assembly of mitochondrial respiratory chain complex IV (cytochrome c oxidase), specifically promoting copper insertion into cytochrome c oxidase subunit II and facilitating merging of assembly intermediates. Mutations cause mitochondrial complex IV deficiency, nuclear type 22, which follows autosomal recessive inheritance. This gene appears relatively tolerant to loss-of-function variants based on constraint metrics.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.781 OMIM phenotype
Clinical SummaryCOX16
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.78LOEUF
pLI 0.000
Z-score -0.10
OE 1.04 (0.581.78)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.25Z-score
OE missense 0.90 (0.711.15)
48 obs / 53.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.04 (0.581.78)
00.351.4
Missense OE0.90 (0.711.15)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 7 / 6.7Missense obs/exp: 48 / 53.2Syn Z: -0.46
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCOX16-related developmental disorderLOFAR

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

DN
0.78top 25%
GOF
0.6832th %ile
LOF
0.3259th %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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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