SCO1

Chr 17AR

synthesis of cytochrome C oxidase 1

Also known as: MC4DN4, SCOD1

NCBI Gene: 6341ENSG00000133028UniProt: O75880

Mammalian cytochrome c oxidase (COX) catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. In yeast, 2 related COX assembly genes, SCO1 and SCO2 (synthesis of cytochrome c oxidase), enable subunits 1 and 2 to be incorporated into the holoprotein. This gene is the human homolog to the yeast SCO1 gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 4MIM #619048
AR
292
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SCO1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 155 VUS of 292 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.
0.99LOEUF
pLI 0.000
Z-score 1.59
OE 0.55 (0.32–0.99)
Tolerant

Typical tolerance to LoF variation

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.
-0.20Z-score
OE missense 1.04 (0.92–1.18)
177 obs / 169.8 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.0.55 (0.32–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.92–1.18)
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.1.08
0≤1.21.6
LoF obs/exp: 8 / 14.6Missense obs/exp: 177 / 169.8Syn Z: -0.54

ClinVar Variant Classifications

292 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic9
VUS155
Likely Benign71
Benign32
Conflicting10
15
Pathogenic
9
Likely Pathogenic
155
VUS
71
Likely Benign
32
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
12
0
15
Likely Pathogenic
6
2
1
0
9
VUS
2
114
30
9
155
Likely Benign
0
3
33
35
71
Benign
0
0
32
0
32
Conflicting
—10
Total1012010844292

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

View in ClinVar →

Protein Context — Lollipop Plot

SCO1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SCO1-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 4

MIM #619048

Molecular basis of disorder known

Autosomal recessive
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
Loss of function of Sco1 and its interaction with cytochrome c oxidase.
Stiburek L et al.·Am J Physiol Cell Physiol
2009
The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c Oxidase.
Swaminathan AB et al.·Biomolecules
2022Review
Unexpected vascular enrichment of SCO1 over SCO2 in mammalian tissues: implications for human mitochondrial disease.
Brosel S et al.·Am J Pathol
2010
Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency.
Horvath R et al.·Biochem Biophys Res Commun
2000
Selective divalent copper chelation for the treatment of diabetes mellitus.
Cooper GJ·Curr Med Chem
2012Review
Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase.
Leary SC et al.·Hum Mol Genet
2004
Defects in mitochondrial respiratory complexes III and IV, and human pathologies.
Borisov VB·Mol Aspects Med
2002Review
The P174L mutation in human Sco1 severely compromises Cox17-dependent metallation but does not impair copper binding.
Cobine PA et al.·J Biol Chem
2006
Cytochrome c oxidase deficiency.
Shoubridge EA·Am J Med Genet
2001Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Heart is the most susceptible organ in an isogenic background to loss of function mutations in the mitochondrial metallochaperone SCO1.
Ghosh S et al.·Hum Mol Genet
2025🔓 Open Access
[Role of SCO1 in regulating microglial mitochondrial copper accumulation in neurological damage of mice exposed to lead and high-glucose diet].
Wang Z et al.·Wei Sheng Yan Jiu
2025
Lymphopoiesis is attenuated upon hepatocyte-specific deletion of the cytochrome c oxidase assembly factor Sco1.
Pioli KT et al.·iScience
2025🔓 Open Access
Endocrinological features and epileptic encephalopathy in COX deficiency due to SCO1 mutations: case series and review of literature.
Barbato A et al.·Endocr Connect
2024🔓 Open AccessReview
Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex.
Xie L et al.·Cell Rep
2022🔓 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