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SCO1

synthesis of cytochrome C oxidase 1, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 17:10672473-10698375

Previous symbols: [ "SCOD1" ]

Links

ENSG00000133028NCBI:6341OMIM:603644HGNC:10603Uniprot:O75880AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • cytochrome-c oxidase deficiency disease (Definitive), mode of inheritance: AR
  • mitochondrial complex 4 deficiency, nuclear type 4 (Strong), mode of inheritance: AR
  • mitochondrial complex 4 deficiency, nuclear type 4 (Moderate), mode of inheritance: AR
  • mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Mitochondrial complex IV deficiency, nuclear type 4ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Attention deficit-hyperactivity disorder, susceptibility to refers to a susceptibility locus and/or evidence or clinical applicability unclearBiochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic11013136; 22231385

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCO1 gene.

  • not provided (129 variants)
  • Cytochrome-c oxidase deficiency disease (48 variants)
  • Leigh syndrome (46 variants)
  • Mitochondrial complex 4 deficiency, nuclear type 4 (24 variants)
  • Inborn genetic diseases (16 variants)
  • not specified (13 variants)
  • Cytochrome-c oxidase deficiency disease;Infantile encephalopathy (2 variants)
  • SCO1-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCO1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
6
clinvar
21
clinvar
27
missense
2
clinvar
62
clinvar
3
clinvar
67
nonsense
2
clinvar
2
start loss
2
clinvar
2
frameshift
2
clinvar
2
clinvar
1
clinvar
5
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
4
3
7
non coding
12
clinvar
19
clinvar
27
clinvar
58
Total 2 5 86 43 27

Highest pathogenic variant AF is 0.0000197

Variants in SCO1

This is a list of pathogenic ClinVar variants found in the SCO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
17-10680388-T-C Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 12, 2018)891558
17-10680397-G-C Cytochrome-c oxidase deficiency disease • Leigh syndrome Benign (Jan 12, 2018)321780
17-10680517-GT-G Leigh syndrome • Cytochrome-c oxidase deficiency disease Uncertain significance (Jun 14, 2016)321781
17-10680525-T-C Leigh syndrome • Cytochrome-c oxidase deficiency disease Uncertain significance (Jan 13, 2018)321782
17-10680593-A-G Leigh syndrome • Cytochrome-c oxidase deficiency disease Uncertain significance (Jan 13, 2018)891822
17-10680716-T-C Leigh syndrome • Cytochrome-c oxidase deficiency disease Uncertain significance (Jan 13, 2018)321783
17-10680770-G-C Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 13, 2018)321784
17-10680793-G-A Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 13, 2018)889379
17-10680799-T-T Leigh syndrome • Cytochrome-c oxidase deficiency disease Benign (Jun 14, 2018)321785
17-10680809-G-A Leigh syndrome • Cytochrome-c oxidase deficiency disease Benign/Likely benign (Jul 09, 2018)321786
17-10680834-G-A Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 13, 2018)321787
17-10680847-A-G Cytochrome-c oxidase deficiency disease • Leigh syndrome Benign/Likely benign (Jul 09, 2018)321788
17-10680849-A-T Leigh syndrome Likely benign (Jan 13, 2018)890068
17-10680992-T-C Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 13, 2018)321789
17-10681038-T-C Leigh syndrome • Cytochrome-c oxidase deficiency disease Uncertain significance (Jan 13, 2018)890644
17-10681039-T-C Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 12, 2018)890645
17-10681058-T-G Cytochrome-c oxidase deficiency disease • Leigh syndrome Uncertain significance (Jan 13, 2018)321790
17-10681101-C-T not specified Likely benign (May 01, 2017)380438
17-10681144-A-T not specified • Mitochondrial complex 4 deficiency, nuclear type 4 Uncertain significance (Apr 26, 2022)811095
17-10681157-T-C Cytochrome-c oxidase deficiency disease • Leigh syndrome • Mitochondrial complex 4 deficiency, nuclear type 4 Conflicting classifications of pathogenicity (Aug 10, 2023)321791
17-10681175-C-T Uncertain significance (Aug 22, 2022)2430904
17-10681177-T-C Inborn genetic diseases Uncertain significance (Aug 13, 2021)2244554
17-10681190-G-A Uncertain significance (Nov 20, 2023)2716117
17-10681201-T-C Inborn genetic diseases Uncertain significance (Jun 05, 2023)2556511
17-10681219-G-A Inborn genetic diseases Uncertain significance (May 08, 2023)2545273

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCO1protein_codingprotein_codingENST00000255390 618039
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0002230.9231257130351257480.000139
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1961771701.040.000008491920
Missense in Polyphen4155.7870.73494677
Synonymous-0.5367367.41.080.00000359603
Loss of Function1.59814.60.5497.09e-7175

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001190.000119
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0002290.000229
Middle Eastern0.000.00
South Asian0.0001960.000196
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Copper metallochaperone essential for the maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). Not required for the synthesis of MT-CO2/COX2 but plays a crucial role in stabilizing MT-CO2/COX2 during its subsequent maturation. Involved in transporting copper to the Cu(A) site on MT-CO2/COX2 (PubMed:15659396, PubMed:16735468, PubMed:17189203, PubMed:19336478, PubMed:15229189). Plays an important role in the regulation of copper homeostasis by controlling the abundance and cell membrane localization of copper transporter CTR1 (By similarity). {ECO:0000250|UniProtKB:Q5SUC9, ECO:0000269|PubMed:15229189, ECO:0000269|PubMed:15659396, ECO:0000269|PubMed:16735468, ECO:0000269|PubMed:17189203, ECO:0000269|PubMed:19336478}.;
Pathway
Electron Transport Chain;Copper homeostasis;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

pRec
0.144

Intolerance Scores

loftool
0.208
rvis_EVS
-0.18
rvis_percentile_EVS
39.95

Haploinsufficiency Scores

pHI
0.0396
hipred
Y
hipred_score
0.638
ghis
0.583

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.751

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sco1
Phenotype
growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype;

Gene ontology

Biological process
generation of precursor metabolites and energy;copper ion transport;cellular copper ion homeostasis;respiratory chain complex IV assembly;mitochondrial respiratory chain complex IV assembly;negative regulation of proteasomal protein catabolic process
Cellular component
mitochondrion;myofibril;integral component of mitochondrial inner membrane;host cell mitochondrial intermembrane space
Molecular function
copper ion binding;protein binding