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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SCO1
synthesis of cytochrome C oxidase 1
Chromosome 17 Β· 17p13.1
NCBI Gene: 6341Ensembl: ENSG00000133028.13HGNC: HGNC:10603UniProt: O75880
83PubMed Papers
21Diseases
0Drugs
12Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrial respiratory chain complex IV assemblymitochondrionmitochondrial inner membranemyofibrilmitochondrial complex IV deficiency, nuclear type 4leigh syndrome due to mitochondrial complex iv deficiencyIsolated cytochrome C oxidase deficiencyneurodegenerative disease
✦AI Summary

SCO1 (synthesis of cytochrome c oxidase 1) is a mitochondrial copper metallochaperone essential for cytochrome c oxidase (COX) biogenesis. SCO1 functions as a copper-binding protein with conserved cysteines and histidyl residues that coordinate both Cu(I) and Cu(II) ions 1. Together with its paralog SCO2, SCO1 mediates copper delivery to the Cu(A) site of COX subunit II (MT-CO2/COX2) during COX assembly 23. SCO1 and SCO2 have non-overlapping, cooperative functions, with SCO2 acting upstream to facilitate CO II synthesis and serving as a thiol-disulfide oxidoreductase for SCO1's copper-coordinating cysteines 3. In this model, COX17 delivers copper to SCO2, which transfers it to SCO1 for subsequent delivery to the CuA site 2. SCO1 mutations impair copper binding affinity and redox properties, reducing copper transfer efficiency to COX 4. Mutations in SCO1 cause mitochondrial complex IV deficiency with tissue-specific phenotypes 5. Loss of scox function in Drosophila demonstrates that intact COX assembly and activity are required for processes dependent on adequate energy supply 6. SCO1 plays an important role in copper homeostasis regulation through effects on copper transporter CTR1 abundance and localization.

Sources cited
1
SCO1 functions as a copper-binding protein with conserved cysteines and histidyl residues that bind Cu(I) and Cu(II) ions
PMID: 16091356
2
SCO1 and SCO2 have cooperative functions in copper delivery to COX; COX17 delivers copper to SCO2, which transfers to SCO1 for CuA site maturation
PMID: 15229189
3
SCO2 acts upstream of SCO1 for CO II synthesis and functions as thiol-disulfide oxidoreductase for SCO1's copper-coordinating cysteines
PMID: 19336478
4
SCO1 mutations alter structure around metal-binding site, affecting copper(I) binding affinity and reducing copper transfer efficiency
PMID: 17182746
5
SCO1 mutations are associated with mitochondrial COX deficiency disorders
PMID: 11027508
6
Loss of SCO function impairs COX assembly and activity, affecting processes dependent on adequate energy supply
PMID: 20388558
7
SCO1 is involved in copper metabolism pathways affecting mitochondrial function
PMID: 37055935
Disease Associationsβ“˜21
mitochondrial complex IV deficiency, nuclear type 4Open Targets
0.78Strong
leigh syndrome due to mitochondrial complex iv deficiencyOpen Targets
0.55Moderate
Isolated cytochrome C oxidase deficiencyOpen Targets
0.51Moderate
neurodegenerative diseaseOpen Targets
0.48Moderate
mitochondrial diseaseOpen Targets
0.37Weak
fatal infantile encephalocardiomyopathyOpen Targets
0.37Weak
Leigh syndromeOpen Targets
0.19Weak
genetic disorderOpen Targets
0.19Weak
respiratory system diseaseOpen Targets
0.03Suggestive
pulmonary arterial hypertensionOpen Targets
0.02Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.01Suggestive
Infantile encephalopathyOpen Targets
0.01Suggestive
small cell osteogenic sarcomaOpen Targets
0.01Suggestive
Decreased total leukocyte countOpen Targets
0.01Suggestive
Mungan syndromeOpen Targets
0.01Suggestive
EncephalopathyOpen Targets
0.01Suggestive
hypertrophic cardiomyopathyOpen Targets
0.01Suggestive
developmental and epileptic encephalopathyOpen Targets
0.01Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.01Suggestive
Epileptic encephalopathyOpen Targets
0.01Suggestive
Mitochondrial complex IV deficiency, nuclear type 4UniProt
Pathogenic Variants12
NM_004589.4(SCO1):c.261del (p.Ser88fs)Pathogenic
not provided|Mitochondrial complex IV deficiency, nuclear type 4
β˜…β˜…β˜†β˜†2026β†’ Residue 88
NM_004589.4(SCO1):c.364_364+1delPathogenic
Mitochondrial complex IV deficiency, nuclear type 4|not provided
β˜…β˜…β˜†β˜†2025
NM_004589.4(SCO1):c.227G>A (p.Trp76Ter)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 4
β˜…β˜…β˜†β˜†2025β†’ Residue 76
NM_004589.4(SCO1):c.551del (p.Val184fs)Pathogenic
not provided|Mitochondrial complex IV deficiency, nuclear type 4
β˜…β˜…β˜†β˜†2024β†’ Residue 184
NM_004589.4(SCO1):c.521C>T (p.Pro174Leu)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 4|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 174
NM_004589.4(SCO1):c.685G>A (p.Gly229Ser)Likely pathogenic
Mitochondrial complex IV deficiency, nuclear type 1
β˜…β˜†β˜†β˜†2025β†’ Residue 229
NM_004589.4(SCO1):c.385C>T (p.Arg129Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 129
NM_004589.4(SCO1):c.32_33dup (p.Met12fs)Likely pathogenic
Mitochondrial complex IV deficiency, nuclear type 4
β˜…β˜†β˜†β˜†2024β†’ Residue 12
NM_004589.4(SCO1):c.269_270del (p.Pro90fs)Likely pathogenic
Mitochondrial complex IV deficiency, nuclear type 4
β˜…β˜†β˜†β˜†2024β†’ Residue 90
NM_004589.4(SCO1):c.348del (p.Glu118fs)Likely pathogenic
Mitochondrial complex IV deficiency, nuclear type 4
β˜…β˜†β˜†β˜†2024β†’ Residue 118
NM_004589.4(SCO1):c.263dup (p.Lys89fs)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 1
β˜…β˜†β˜†β˜†2018β†’ Residue 89
NM_004589.4(SCO1):c.394G>A (p.Gly132Ser)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 4
β˜†β˜†β˜†β˜†2009β†’ Residue 132
View on ClinVar β†—
Related Genes
COX10Protein interaction98%COX11Protein interaction98%COX15Protein interaction98%COX1Protein interaction98%COX2Protein interaction98%UQCRFS1Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Heart
84%
Brain
53%
Lung
47%
Bone Marrow
45%
Ovary
38%
Gene Interaction Network
Click a node to explore
SCO1COX10COX11COX15COX1COX2UQCRFS1
PROTEIN STRUCTURE
Preparing viewer…
PDB2GGT Β· 2.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.21LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.80 [0.55–1.21]
RankingsWhere SCO1 stands among ~20K protein-coding genes
  • #5,755of 20,598
    Most Researched83
  • #2,675of 5,498
    Most Pathogenic Variants12
  • #12,689of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedSCO1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Copper metabolism in cell death and autophagy.
PMID: 37055935
Autophagy Β· 2023
1.00
2
Human Sco1 and Sco2 function as copper-binding proteins.
PMID: 16091356
J Biol Chem Β· 2005
0.90
3
Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase.
PMID: 15229189
Hum Mol Genet Β· 2004
0.80
4
Genetic, functional and evolutionary characterization of scox, the Drosophila melanogaster ortholog of the human SCO1 gene.
PMID: 20388558
Mitochondrion Β· 2010
0.70
5
Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency.
PMID: 11027508
Biochem Biophys Res Commun Β· 2000
0.60