SCO1

Summary

SCO1 (synthesis of cytochrome C oxidase 1, HGNC:10603) is a protein-coding gene on chromosome 17p13.1, encoding Cytochrome c oxidase assembly factor SCO1 (O75880). Copper metallochaperone essential for the maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). It is a selective cancer dependency (DepMap: 17.4% of cell lines).

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.

Source: NCBI Gene 6341 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 229 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 61
• Cancer dependency (DepMap): dependent in 17.4% of screened cell lines
• MANE Select transcript: NM_004589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10603
Approved symbol	SCO1
Name	synthesis of cytochrome C oxidase 1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000133028
Ensembl biotype	protein_coding
OMIM	603644
Entrez	6341

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000255390, ENST00000577335, ENST00000577427, ENST00000579396, ENST00000582053, ENST00000901622, ENST00000901623, ENST00000901624, ENST00000901625

RefSeq mRNA: 1 — MANE Select: NM_004589 NM_004589

CCDS: CCDS11158

Canonical transcript exons

ENST00000255390 — 6 exons

Exon	Start	End
ENSE00000907741	10686727	10686842
ENSE00000907742	10691872	10691964
ENSE00000907743	10692764	10692961
ENSE00001523689	10697235	10697533
ENSE00003635579	10695741	10695831
ENSE00003705723	10672474	10681253

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 93.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7903 / max 97.7120, expressed in 1814 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164615	20.7903	1814

Top tissues by expression

257 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	93.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.54	gold quality
mucosa of transverse colon	UBERON:0004991	91.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.10	gold quality
ileal mucosa	UBERON:0000331	89.24	gold quality
myocardium	UBERON:0002349	89.15	gold quality
tibialis anterior	UBERON:0001385	88.97	silver quality
heart left ventricle	UBERON:0002084	88.93	gold quality
calcaneal tendon	UBERON:0003701	88.78	gold quality
cardiac ventricle	UBERON:0002082	88.63	gold quality
gastrocnemius	UBERON:0001388	88.25	gold quality
right lobe of liver	UBERON:0001114	88.20	gold quality
kidney epithelium	UBERON:0004819	88.09	gold quality
muscle of leg	UBERON:0001383	88.03	gold quality
adrenal tissue	UBERON:0018303	87.88	gold quality
right adrenal gland cortex	UBERON:0035827	87.85	gold quality
right adrenal gland	UBERON:0001233	87.61	gold quality
heart	UBERON:0000948	87.56	gold quality
deltoid	UBERON:0001476	87.55	gold quality
right atrium auricular region	UBERON:0006631	87.45	gold quality
cardiac atrium	UBERON:0002081	87.35	gold quality
adult mammalian kidney	UBERON:0000082	87.26	gold quality
muscle organ	UBERON:0001630	87.25	gold quality
left adrenal gland	UBERON:0001234	86.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.78	gold quality
transverse colon	UBERON:0001157	86.64	gold quality
left adrenal gland cortex	UBERON:0035825	86.32	gold quality
adrenal gland	UBERON:0002369	86.19	gold quality
duodenum	UBERON:0002114	86.01	gold quality
rectum	UBERON:0001052	85.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting SCO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-7112-3P	97.67	68.77	948

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• SCO1 facilitates the transfer of copper from SCO2 to the CuA site at an early stage of COX assembly in mitochondria. (PMID:15229189)
• data suggest that both Cu(I) and Cu(II) binding are critical for normal Sco function. (PMID:16091356)
• Cox17-mediated copper metallation of Sco1, as well as the subsequent failure of Cu(A) site maturation, is the basis for the inefficient assembly of the cytochrome c oxidase complex in SCO1 patients (PMID:16520371)
• Sco1 has evolved to bind a metal atom via the di-Cys motif to act as a copper chaperone, the oxidized form of the nickel-bound protein suggests that it may also maintain the thioredoxin function. (PMID:16735468)
• These results suggest a mitochondrial pathway for the regulation of cellular copper content that involves signaling through SCO1 and SCO2, perhaps by their thiol redox or metal-binding state. (PMID:17189203)
• Cu(I)HCox17(2S-S), i.e., the copper-loaded form of the protein, can transfer simultaneously copper(I) and two electrons to the human cochaperone Sco1 (HSco1) in the oxidized state, i.e., with its metal-binding cysteines forming a disulfide bond. (PMID:18458339)
• a fraction of Sco1 physically associates with the cytochrome c oxidase complex in human muscle mitochondria, suggesting a possible direct relationship between CcO and the regulation of cellular copper homeostasis (PMID:19295170)
• SCO2 acts upstream of SCO1, and that it is indispensable for CO II synthesis. (PMID:19336478)
• Results describe the tissue distribution of SCO1 and SCO2 in mouse and human tissues. (PMID:20864674)
• COX19 is necessary for the transduction of a SCO1-dependent mitochondrial redox signal that regulates ATP7A-mediated cellular copper efflux. (PMID:23345593)
• COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase. (PMID:24403053)
• Results find that COA6 associates with COX2 and is crucial for its maturation and complex IV biogenesis. Also, COA6 interacts with the copper chaperone SCO1 which indicates that COA6 is intrinsically involved in the copper delivery process for COX2. (PMID:26160915)
• Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. (PMID:26351686)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sco1	ENSDARG00000067593
mus_musculus	Sco1	ENSMUSG00000069844
rattus_norvegicus	Sco1	ENSRNOG00000072761
drosophila_melanogaster	Scox	FBGN0262467
caenorhabditis_elegans		WBGENE00015297

Paralogs (1): SCO2 (ENSG00000284194)

Protein

Protein identifiers

Cytochrome c oxidase assembly factor SCO1 — O75880 (reviewed: O75880)

All UniProt accessions (3): O75880, J3QL56, J3QR42

UniProt curated annotations — full annotation on UniProt →

Function. Copper metallochaperone essential for the maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). Together with SCO2, involved in delivering copper to the Cu(A) site on MT-CO2/COX2. Plays an important role in the regulation of copper homeostasis by controlling the abundance and cell membrane localization of copper transporter CTR1.

Subunit / interactions. Homodimer. Interacts with COA6. Found in a complex with TMEM177, COX20, COA6, MT-CO2/COX2, COX18 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20 in a MT-CO2/COX2- and COX18-dependent manner. Interacts with COX16.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Predominantly expressed in tissues characterized by high rates of oxidative phosphorylation (OxPhos), including muscle, heart, and brain.

Disease relevance. Mitochondrial complex IV deficiency, nuclear type 4 (MC4DN4) [MIM:619048] An autosomal recessive mitochondrial disorder characterized by hypotonia, encephalopathy, metabolic acidosis, poor feeding, hepatomegaly, and hypertrophic cardiomyopathy in some patients. Death occurs in infancy. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SCO1/2 family.

RefSeq proteins (1): NP_004580* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003782	SCO1/SenC	Family
IPR017276	Synth_of_cyt-c-oxidase_Sco1/2	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF02630

UniProt features (33 total): strand 10, helix 8, binding site 3, sequence variant 2, topological domain 2, turn 2, region of interest 2, transit peptide 1, chain 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2GGT	X-RAY DIFFRACTION	2.4
1WP0	X-RAY DIFFRACTION	2.8
2GQK	SOLUTION NMR
2GQL	SOLUTION NMR
2GQM	SOLUTION NMR
2GT5	SOLUTION NMR
2GT6	SOLUTION NMR
2GVP	SOLUTION NMR
2HRF	SOLUTION NMR
2HRN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75880-F1	77.95	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 169; 173; 260

Disulfide bonds (1): 169–173

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-611105	Respiratory electron transport

MSigDB gene sets: 155 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, WEI_MYCN_TARGETS_WITH_E_BOX, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_MONOATOMIC_ION_HOMEOSTASIS, BASAKI_YBX1_TARGETS_UP, WONG_MITOCHONDRIA_GENE_MODULE, GOBP_COPPER_ION_HOMEOSTASIS, DANG_BOUND_BY_MYC, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, GOCC_ORGANELLE_INNER_MEMBRANE, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, BENPORATH_MYC_MAX_TARGETS

GO Biological Process (3): intracellular copper ion homeostasis (GO:0006878), mitochondrial respiratory chain complex IV assembly (GO:0033617), respiratory chain complex IV assembly (GO:0008535)

GO Molecular Function (4): copper ion binding (GO:0005507), copper chaperone activity (GO:0016531), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), myofibril (GO:0030016), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Respiratory electron transport	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular monoatomic cation homeostasis	1
copper ion homeostasis	1
mitochondrion	1
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
cytochrome complex assembly	1
transition metal ion binding	1
copper ion binding	1
metallochaperone activity	1
binding	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
contractile muscle fiber	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCO1	COX17	Q14061	989
SCO1	COX10	Q12887	950
SCO1	SURF1	Q15526	948
SCO1	MT-CO2	P00403	925
SCO1	COX11	Q9Y6N1	916
SCO1	COX15	Q7KZN9	910
SCO1	COA6	Q5JTJ3	905
SCO1	COX6B1	P14854	870
SCO1	MT-CO1	P00395	828
SCO1	MT-CO3	P00414	795
SCO1	ATOX1	O00244	789
SCO1	TACO1	Q9BSH4	773
SCO1	COA5	Q86WW8	750
SCO1	FASTKD2	Q9NYY8	740
SCO1	LRPPRC	P42704	703

IntAct

58 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
WDR19	TULP3	psi-mi:“MI:0914”(association)	0.860
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
PRELID3B	TRIAP1	psi-mi:“MI:0914”(association)	0.710
SCO1	COX17	psi-mi:“MI:0407”(direct interaction)	0.660
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
SCO1	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
COMT	SCO1	psi-mi:“MI:0915”(physical association)	0.560
SCO1	E6	psi-mi:“MI:0915”(physical association)	0.370
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
PPEF1	ILVBL	psi-mi:“MI:0914”(association)	0.350
STK38L		psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
OPA3	TIMM23	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
OPA3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
CAV2	SURF4	psi-mi:“MI:0914”(association)	0.350
CAV2	CYB5B	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
C3orf62	SCO1	psi-mi:“MI:0914”(association)	0.350
NTRK3	ILVBL	psi-mi:“MI:0914”(association)	0.350
CALM2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (188): SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), SCO1 (Negative Genetic), SCO1 (Negative Genetic)

ESM2 similar proteins: A1A4J8, A6H784, D3ZS74, D4A6D7, E9QBI7, O42899, O43819, O60341, O75880, P00258, P10109, P23833, P24483, P30048, P38072, Q05B51, Q0VCH8, Q12931, Q2KHU5, Q2NKY8, Q2TBI4, Q3ULF4, Q4VAE3, Q5EA41, Q5REY3, Q5RH02, Q5SUC9, Q69ZP3, Q6DKK2, Q6PI78, Q6ZQ88, Q7ZUC7, Q8BMS4, Q8JZQ2, Q8LAL0, Q8N490, Q8VCL2, Q920A7, Q95N00, Q96HS1

Diamond homologs: A1A4J8, A6H784, O42899, O43819, O75880, P23833, P38072, P47206, Q1RIN4, Q1RKK4, Q4UKW2, Q4UNH4, Q52720, Q5RH02, Q5SUC9, Q68WF1, Q8LAL0, Q8VCL2, Q8VYP0, Q92H76, Q92JM5, Q9ZCW7, Q9ZEB4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein degradation	5	13.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to ethanol	5	12.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

229 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	114
Likely benign	52
Benign	28

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1034098	NM_004589.4(SCO1):c.263dup (p.Lys89fs)	Pathogenic
120177	NM_004589.4(SCO1):c.394G>A (p.Gly132Ser)	Pathogenic
4703181	NM_004589.4(SCO1):c.385C>T (p.Arg129Ter)	Pathogenic
6177	NM_004589.4(SCO1):c.364_364+1del	Pathogenic
3581622	NM_004589.4(SCO1):c.348del (p.Glu118fs)	Likely pathogenic
3581625	NM_004589.4(SCO1):c.269_270del (p.Pro90fs)	Likely pathogenic
4687312	NM_004589.4(SCO1):c.685G>A (p.Gly229Ser)	Likely pathogenic

SpliceAI

1257 predictions. Top by Δscore:

Variant	Effect	Δscore
17:10686719:TTAC:T	donor_loss	1.0000
17:10686720:TACT:T	donor_loss	1.0000
17:10686721:A:AC	donor_gain	1.0000
17:10686722:C:CC	donor_gain	1.0000
17:10686723:TCAC:T	donor_loss	1.0000
17:10686724:CAC:C	donor_loss	1.0000
17:10686725:A:AC	donor_gain	1.0000
17:10686726:C:CG	donor_gain	1.0000
17:10686726:CT:C	donor_gain	1.0000
17:10686726:CTA:C	donor_gain	1.0000
17:10686726:CTAT:C	donor_gain	1.0000
17:10686838:AAATT:A	acceptor_gain	1.0000
17:10686839:AATT:A	acceptor_gain	1.0000
17:10686841:TT:T	acceptor_gain	1.0000
17:10686843:C:CC	acceptor_gain	1.0000
17:10691867:AATAC:A	donor_loss	1.0000
17:10691868:ATACC:A	donor_loss	1.0000
17:10691869:TACC:T	donor_loss	1.0000
17:10691870:A:T	donor_loss	1.0000
17:10691871:C:CT	donor_loss	1.0000
17:10691871:CCTT:C	donor_gain	1.0000
17:10691873:TTTC:T	donor_gain	1.0000
17:10692960:CT:C	acceptor_gain	1.0000
17:10692963:T:C	acceptor_gain	1.0000
17:10695739:A:AC	donor_gain	1.0000
17:10695740:C:CC	donor_gain	1.0000
17:10695740:CT:C	donor_gain	1.0000
17:10695740:CTCT:C	donor_gain	1.0000
17:10686722:CT:C	donor_gain	0.9900
17:10686722:CTCA:C	donor_gain	0.9900

AlphaMissense

1941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:10692828:G:C	F166L	1.000
17:10692828:G:T	F166L	1.000
17:10692830:A:G	F166L	1.000
17:10686838:A:C	F220L	0.998
17:10686838:A:T	F220L	0.998
17:10686840:A:G	F220L	0.998
17:10692821:A:G	C169R	0.998
17:10691905:C:G	D208H	0.997
17:10691921:G:C	S202R	0.997
17:10691921:G:T	S202R	0.997
17:10691923:T:G	S202R	0.997
17:10692834:A:C	F164L	0.997
17:10692834:A:T	F164L	0.997
17:10692836:A:G	F164L	0.997
17:10681245:G:C	H260Q	0.996
17:10681245:G:T	H260Q	0.996
17:10691904:T:G	D208A	0.996
17:10692809:A:G	C173R	0.996
17:10692820:C:T	C169Y	0.996
17:10681247:G:C	H260D	0.995
17:10692808:C:T	C173Y	0.995
17:10692819:G:C	C169W	0.995
17:10692829:A:G	F166S	0.995
17:10692830:A:T	F166I	0.995
17:10691904:T:A	D208V	0.994
17:10691925:A:T	I201N	0.994
17:10692796:A:G	L177P	0.994
17:10692807:A:C	C173W	0.994
17:10692832:C:T	G165D	0.994
17:10692851:A:G	W159R	0.994

dbSNP variants (sampled 300 via entrez): RS1000007306 (17:10685131 T>C), RS1000123198 (17:10685376 T>C), RS1000168686 (17:10696140 G>A), RS1000203612 (17:10691660 A>G), RS1000285433 (17:10689875 T>C), RS1000340334 (17:10691884 T>C), RS1000391063 (17:10695899 T>C,G), RS1000450691 (17:10686031 G>A,C), RS1000634267 (17:10693324 T>C), RS1000647331 (17:10675597 C>A,T), RS1000866525 (17:10675303 G>A,C), RS1000886467 (17:10687560 T>C), RS1000906559 (17:10698501 G>A), RS1000940988 (17:10681317 T>A,G), RS1001123520 (17:10686445 G>A)

Disease associations

OMIM: gene MIM:603644 | disease phenotypes: MIM:220110, MIM:619048, MIM:256000, MIM:605637

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex IV deficiency, nuclear type 4	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (4): mitochondrial complex IV deficiency, nuclear type 1 (MONDO:0700250), mitochondrial complex IV deficiency, nuclear type 4 (MONDO:0033636), Leigh syndrome (MONDO:0009723), myopathy, proximal, and ophthalmoplegia (MONDO:0011577)

Orphanet (3): Leigh syndrome (Orphanet:506), Childhood-onset autosomal recessive myopathy with external ophthalmoplegia (Orphanet:363677), Hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome (Orphanet:79091)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000124	Renal tubular dysfunction
HP:0000218	High palate
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000580	Pigmentary retinopathy
HP:0000597	Ophthalmoparesis
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001348	Brisk reflexes
HP:0001397	Hepatic steatosis
HP:0001410	Decreased liver function
HP:0001427	Mitochondrial inheritance
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001662	Bradycardia
HP:0001712	Left ventricular hypertrophy
HP:0001714	Ventricular hypertrophy
HP:0001903	Anemia
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000410_2	Malaria	7.000000e-07
GCST002183_2	Relative hand skill in reading disability	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520
C565311	Inclusion Body Myopathy 3, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	affects abundance, affects oxidation, affects binding, affects folding, decreases abundance	4
bisphenol A	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Smoke	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
bathocuproine sulfonate	increases oxidation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Coal	decreases expression, increases abundance	1
Folic Acid	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	decreases expression	1
Nickel	affects binding, affects folding	1
Ozone	affects expression, increases abundance	1
Paraquat	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GH	Abcam HEK293T SCO1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

14 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells