SCO2

Chr 22ARAD

synthesis of cytochrome C oxidase 2

NCBI Gene: 9997ENSG00000284194UniProt: O43819

Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2); together with SCO1, facilitates the incorporation of copper into the Cu(A) site of MT-CO2/COX2 (PubMed:15229189, PubMed:17189203, PubMed:19336478, PubMed:35750769). Could also act as a thiol-disulfide oxidoreductase to regulate the redox state of the cysteines in SCO1 during maturation of MT-CO2/COX2 (PubMed:19336478)

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 2MIM #604377
AR
Myopia 6MIM #608908
AD
993
ClinVar variants
66
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SCO2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 199 VUS of 993 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.
1.76LOEUF
pLI 0.000
Z-score -0.21
OE 1.08 (0.65–1.76)
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.
-1.61Z-score
OE missense 1.36 (1.22–1.52)
219 obs / 161.4 exp
Tolerant

Tolerant to missense variation

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.1.08 (0.65–1.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.36 (1.22–1.52)
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.1.21
0≤1.21.6
LoF obs/exp: 9 / 8.4Missense obs/exp: 219 / 161.4Syn Z: -1.39

ClinVar Variant Classifications

993 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic16
VUS199
Likely Benign223
Benign4
Conflicting7
50
Pathogenic
16
Likely Pathogenic
199
VUS
223
Likely Benign
4
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
0
31
0
50
Likely Pathogenic
9
2
5
0
16
VUS
3
179
11
6
199
Likely Benign
0
6
18
199
223
Benign
2
0
1
1
4
Conflicting
—7
Total3318766206499

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

View in ClinVar →

Protein Context — Lollipop Plot

SCO2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SCO2-related myopia

strong
ADUndeterminedUncertain
Eye
G2P ↗

SCO2-related fatal infantile cardioencephalomyopathy due to cytochrome c oxidase 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 2

MIM #604377

Molecular basis of disorder known

Autosomal recessive

Myopia 6

MIM #608908

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
Unveiling ac4C modification pattern: a prospective target for improving the response to immunotherapeutic strategies in melanoma.
Liu J et al.·J Transl Med
2025
Near-infrared oximetry of the brain.
Madsen PL et al.·Prog Neurobiol
1999Review
Mitochondrial cardioencephalomyopathy due to a novel SCO2 mutation in a Brazilian patient: case report and literature review.
Gurgel-Giannetti J et al.·JAMA Neurol
2013Review
TCF19 and p53 regulate transcription of TIGAR and SCO2 in HCC for mitochondrial energy metabolism and stress adaptation.
Mondal P et al.·FASEB J
2021
The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c Oxidase.
Swaminathan AB et al.·Biomolecules
2022Review
Defects in mitochondrial respiratory complexes III and IV, and human pathologies.
Borisov VB·Mol Aspects Med
2002Review
Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency.
Darin N et al.·Neuropediatrics
2003Review
Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality.
Tay SK et al.·Arch Neurol
2004Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Bulk and Single-Cell Transcriptomics Reveal That SCO2 Drives Psoriasis via Activating CCR7+ Dendritic Cell.
Chen D et al.·Int J Mol Sci
2026🔓 Open Access
4E analysis of supercritical carbon dioxide (sCO2) cycles: evaluating energy, exergy, environmental sustainability, and economic impacts in combined systems.
Ahmadi M et al.·Sci Rep
2025🔓 Open Access
3E analysis of sCO2 recuperator cycle with multi effect desalination and organic Rankine cycle to enhance environmental sustainability.
Ahmadi M et al.·Sci Rep
2025🔓 Open Access
Biohythane Production in Hydrogen-Oriented Dark Fermentation of Aerobic Granular Sludge (AGS) Pretreated with Solidified Carbon Dioxide (SCO2).
Kazimierowicz J et al.·Int J Mol Sci
2023🔓 Open Access
Protein Transduction Domain-Mediated Delivery of Recombinant Proteins and In Vitro Transcribed mRNAs for Protein Replacement Therapy of Human Severe Genetic Mitochondrial Disorders: The Case of Sco2 Deficiency.
Miliotou AN et al.·Pharmaceutics
2023🔓 Open Access
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