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

ENSG00000133028 ∙ NCBI:6341 ∙ OMIM:603644 ∙ HGNC:10603 ∙ Uniprot:O75880 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 4	AR	General	Genetic 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 unclear	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	11013136; 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	21		27
missense		2	62	3		67
nonsense			2			2
start loss			2			2
frameshift	2	2	1			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			4	3		7
non coding			12	19	27	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		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 12, 2018)
17-10680397-G-C		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Benign (Jan 12, 2018)
17-10680517-GT-G		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jun 14, 2016)
17-10680525-T-C		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
17-10680593-A-G		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-10680716-T-C		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
17-10680770-G-C		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-10680793-G-A		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
17-10680799-T-T		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Benign (Jun 14, 2018)
17-10680809-G-A		Leigh syndrome • Mitochondrial complex IV deficiency, nuclear type 1	Benign/Likely benign (Jul 09, 2018)
17-10680834-G-A		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-10680847-A-G		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Benign/Likely benign (Jul 09, 2018)
17-10680849-A-T		Leigh syndrome	Likely benign (Jan 13, 2018)
17-10680992-T-C		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-10681038-T-C		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-10681039-T-C		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 12, 2018)
17-10681058-T-G		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Uncertain significance (Jan 13, 2018)
17-10681101-C-T		not specified	Likely benign (May 01, 2017)
17-10681144-A-T		not specified • Mitochondrial complex 4 deficiency, nuclear type 4	Uncertain significance (Apr 26, 2022)
17-10681157-T-C		Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome • Mitochondrial complex 4 deficiency, nuclear type 4	Conflicting classifications of pathogenicity (Aug 10, 2023)
17-10681175-C-T			Uncertain significance (Aug 22, 2022)
17-10681177-T-C		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
17-10681190-G-A			Uncertain significance (Nov 20, 2023)
17-10681201-T-C		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
17-10681219-G-A		Inborn genetic diseases	Uncertain significance (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCO1	protein_coding	protein_coding	ENST00000255390	6	18039

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000223	0.923	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.196	177	170	1.04	0.00000849	1920
Missense in Polyphen		41	55.787	0.73494		677
Synonymous	-0.536	73	67.4	1.08	0.00000359	603
Loss of Function	1.59	8	14.6	0.549	7.09e-7	175

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.00	0.00
South Asian	0.000196	0.000196
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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