COX20

Chr 1AR

cytochrome c oxidase assembly factor COX20

Also known as: FAM36A, MC4DN11

NCBI Gene: 116228ENSG00000203667UniProt: Q5RI15OMIM: 614698

This gene encodes a protein that assembles cytochrome C oxidase (complex IV) in the mitochondrial respiratory chain. Autosomal recessive mutations cause mitochondrial complex IV deficiency, presenting with ataxia and muscle hypotonia. The pathogenic mechanism involves loss of function mutations that disrupt complex IV assembly.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.481 OMIM phenotype
Clinical Summary— COX20
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
113 unique Pathogenic / Likely Pathogenic· 79 VUS of 280 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
1.48LOEUF
pLI 0.020
Z-score 0.85
OE 0.59 (0.27–1.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.29Z-score
OE missense 0.89 (0.71–1.13)
51 obs / 57.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.27–1.48)
0≤0.351.4
Missense OE0.89 (0.71–1.13)
0≤0.61.4
Synonymous OE1.29
0≤1.21.6
LoF obs/exp: 3 / 5.1Missense obs/exp: 51 / 57.2Syn Z: -1.01
DN
0.93top 5%
GOF
0.7028th %ile
LOF
0.1498th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

280 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic97
Likely Pathogenic16
VUS79
Likely Benign59
Benign17
Conflicting5
97
Pathogenic
16
Likely Pathogenic
79
VUS
59
Likely Benign
17
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
92
0
97
Likely Pathogenic
7
1
8
0
16
VUS
7
56
16
0
79
Likely Benign
2
4
32
21
59
Benign
0
1
14
2
17
Conflicting
—5
Total176616223273

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

View in ClinVar →

Protein Context — Lollipop Plot

COX20 · 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
Top 4 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