SCO2

Summary

SCO2 (synthesis of cytochrome C oxidase 2, HGNC:10604) is a protein-coding gene on chromosome 22q13.33, encoding Cytochrome c oxidase assembly factor SCO2 (O43819). Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2); together with SCO1, facilitates the incorporation of copper into the Cu(A) site of MT-CO2/COX2.

Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. Human COX is a multimeric protein complex that requires several assembly factors; this gene encodes one of the COX assembly factors. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6.

Source: NCBI Gene 9997 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leigh syndrome (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 87 total — 5 pathogenic, 5 likely-pathogenic
• GTEx eGene: eQTL in 22 tissues, sQTL in 35 (q < 0.05)
• Phenotypes (HPO): 170
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.76 (unconstrained)
• MANE Select transcript: NM_005138

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10604
Approved symbol	SCO2
Name	synthesis of cytochrome C oxidase 2
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SCO1L
Ensembl gene	ENSG00000284194
Ensembl biotype	protein_coding
OMIM	604272
Entrez	9997

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

MANE Select: ENST00000395693

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4

ENST00000395693, ENST00000252785, ENST00000535425, ENST00000543927, ENST00000638598, ENST00000862162, ENST00000862163, ENST00000862164, ENST00000862165, ENST00000862166, ENST00000862167, ENST00000862168, ENST00000862169, ENST00000928020, ENST00001133054

RefSeq mRNA: 4 — MANE Select: NM_005138 NM_001169109, NM_001169110, NM_001169111, NM_005138

CCDS: CCDS14095

Canonical transcript exons

ENST00000395693 — 2 exons

Exon	Start	End
ENSE00001522509	50525472	50525598
ENSE00003902118	50523568	50524424

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8442 / max 59.4095, expressed in 1799 samples.

Highest expression (Bgee): uterine tube, granulocyte, mucosa of transverse colon, monocyte, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SCO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 57 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	4.9e-57	-0.78	22:50525724:T:C
Cells Cultured fibroblasts	sqtl	2.0e-44	+1.19	22:50526017:A:T
Testis	sqtl	4.9e-39	+1.99	22:50531639:C:T
Cells EBV-transformed lymphocytes	sqtl	2.1e-37	+1.25	22:50526017:A:T
Whole Blood	eqtl	1.6e-35	-0.47	22:50525724:T:C
Lung	sqtl	2.4e-25	-0.72	22:50525724:T:C
Colon Transverse	sqtl	2.7e-23	+0.96	22:50526017:A:T
Adipose Visceral Omentum	sqtl	3.6e-20	+0.77	22:50525724:T:C
Esophagus Mucosa	sqtl	2.3e-18	-0.82	22:50526017:A:T
Adipose Subcutaneous	sqtl	4.8e-17	+0.67	22:50525724:T:C
Skin Sun Exposed Lower leg	sqtl	9.1e-17	+0.65	22:50526017:A:T
Skin Not Sun Exposed Suprapubic	sqtl	1.4e-15	+0.72	22:50526017:A:T
Colon Sigmoid	sqtl	3.7e-14	+0.82	22:50526017:A:T
Lung	eqtl	4.2e-14	-0.36	22:50525724:T:C
Esophagus Muscularis	sqtl	2.9e-12	+0.69	22:50526017:A:T
Stomach	sqtl	5.4e-12	+0.88	22:50526017:A:T
Artery Aorta	sqtl	9.8e-11	+0.77	22:50526017:A:T
Spleen	sqtl	4.1e-10	+0.85	22:50526017:A:T
Esophagus Gastroesophageal Junction	sqtl	5.3e-09	+0.78	22:50526017:A:T
Nerve Tibial	sqtl	1.3e-08	-0.42	22:50525724:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
194754	8.3682	1719
194755	2.2973	1178
194756	2.0937	1201
194757	0.0851	17

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.58	gold quality
granulocyte	CL:0000094	97.35	gold quality
mucosa of transverse colon	UBERON:0004991	96.39	gold quality
monocyte	CL:0000576	95.53	gold quality
mononuclear cell	CL:0000842	95.39	gold quality
leukocyte	CL:0000738	94.87	gold quality
gingival epithelium	UBERON:0001949	94.00	gold quality
gingiva	UBERON:0001828	92.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.09	gold quality
cervix squamous epithelium	UBERON:0006922	92.09	gold quality
palpebral conjunctiva	UBERON:0001812	91.46	gold quality
squamous epithelium	UBERON:0006914	90.83	gold quality
periodontal ligament	UBERON:0008266	90.78	gold quality
right lobe of liver	UBERON:0001114	90.01	gold quality
esophagus squamous epithelium	UBERON:0006920	89.95	gold quality
epithelium of bronchus	UBERON:0002031	89.88	gold quality
bronchial epithelial cell	CL:0002328	89.84	gold quality
blood	UBERON:0000178	89.68	gold quality
esophagus mucosa	UBERON:0002469	89.57	gold quality
bronchus	UBERON:0002185	89.32	gold quality
right lung	UBERON:0002167	89.13	gold quality
lower esophagus mucosa	UBERON:0035834	89.04	gold quality
epithelium of esophagus	UBERON:0001976	88.86	gold quality
transverse colon	UBERON:0001157	88.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.61	gold quality
apex of heart	UBERON:0002098	88.27	gold quality
endothelial cell	CL:0000115	88.21	gold quality
parietal pleura	UBERON:0002400	87.94	gold quality
upper lobe of left lung	UBERON:0008952	87.64	gold quality
omental fat pad	UBERON:0010414	87.24	gold quality
peritoneum	UBERON:0002358	87.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.04	gold quality
pleura	UBERON:0000977	87.03	gold quality
nasal cavity mucosa	UBERON:0001826	86.63	gold quality
right adrenal gland	UBERON:0001233	86.61	gold quality
upper lobe of lung	UBERON:0008948	86.60	gold quality
duodenum	UBERON:0002114	86.58	gold quality
oral cavity	UBERON:0000167	86.37	gold quality
left adrenal gland	UBERON:0001234	86.31	gold quality
left adrenal gland cortex	UBERON:0035825	86.30	gold quality
spleen	UBERON:0002106	86.24	gold quality
right adrenal gland cortex	UBERON:0035827	86.10	gold quality
left uterine tube	UBERON:0001303	86.07	gold quality
visceral pleura	UBERON:0002401	85.85	gold quality
colonic mucosa	UBERON:0000317	85.47	gold quality
heart left ventricle	UBERON:0002084	85.39	gold quality
esophagus	UBERON:0001043	85.27	gold quality
adrenal cortex	UBERON:0001235	85.02	gold quality
cardiac ventricle	UBERON:0002082	84.99	gold quality
mammalian vulva	UBERON:0000997	84.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.56	gold quality
colon	UBERON:0001155	84.47	gold quality
large intestine	UBERON:0000059	84.39	gold quality
parotid gland	UBERON:0001831	84.37	gold quality
nasal cavity epithelium	UBERON:0005384	84.31	gold quality
nephron tubule	UBERON:0001231	84.28	gold quality
mouth mucosa	UBERON:0003729	84.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.16	gold quality
stromal cell of endometrium	CL:0002255	84.14	gold quality
jejunal mucosa	UBERON:0000399	84.02	gold quality
decidua	UBERON:0002450	83.79	gold quality
adipose tissue	UBERON:0001013	83.62	gold quality
skin of abdomen	UBERON:0001416	83.59	gold quality
small intestine	UBERON:0002108	83.55	gold quality
minor salivary gland	UBERON:0001830	83.52	gold quality
intestine	UBERON:0000160	83.37	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.28	gold quality
pancreatic ductal cell	CL:0002079	83.22	gold quality
saliva-secreting gland	UBERON:0001044	83.19	gold quality
body of stomach	UBERON:0001161	83.10	gold quality
gastrocnemius	UBERON:0001388	83.04	gold quality
liver	UBERON:0002107	82.99	gold quality
descending thoracic aorta	UBERON:0002345	82.97	gold quality
right atrium auricular region	UBERON:0006631	82.94	gold quality
left coronary artery	UBERON:0001626	82.80	gold quality
metanephros cortex	UBERON:0010533	82.73	gold quality
adrenal gland	UBERON:0002369	82.56	gold quality
skin of leg	UBERON:0001511	82.50	gold quality
connective tissue	UBERON:0002384	82.43	gold quality
cervix epithelium	UBERON:0004801	82.43	gold quality
coronary artery	UBERON:0001621	82.38	gold quality
right coronary artery	UBERON:0001625	82.32	gold quality
penis	UBERON:0000989	82.23	gold quality
zone of skin	UBERON:0000014	82.16	gold quality
prefrontal cortex	UBERON:0000451	82.10	gold quality
heart	UBERON:0000948	81.90	gold quality
sigmoid colon	UBERON:0001159	81.89	gold quality
amniotic fluid	UBERON:0000173	81.80	gold quality
epithelium of nasopharynx	UBERON:0001951	81.80	gold quality
middle temporal gyrus	UBERON:0002771	81.54	gold quality
vermiform appendix	UBERON:0001154	81.49	gold quality
thoracic aorta	UBERON:0001515	81.44	gold quality
adult mammalian kidney	UBERON:0000082	81.43	gold quality
lower esophagus	UBERON:0013473	81.42	gold quality
upper leg skin	UBERON:0004262	81.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.36	gold quality
ascending aorta	UBERON:0001496	81.32	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.26	gold quality
endocervix	UBERON:0000458	81.20	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	351.97
E-MTAB-7052	no	201.13
E-MTAB-4850	no	179.46
E-ANND-3	no	1.55

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	34.3	low
Duodenum	tissue	24.1	high
Colon	tissue	20.6	medium
Salivary gland	tissue	20.0	medium
Frontal cortex	tissue	19.0
Small intestine	tissue	18.5	high
Choroid plexus	tissue	17.6
Liver	tissue	17.2	not detected
Adipose tissue	tissue	15.7	not detected
Vagina	tissue	15.0	medium
Fallopian tube	tissue	14.9	medium
Lung	tissue	13.5	low
Appendix	tissue	12.6	medium
Urinary bladder	tissue	12.1	high
Caudate putamen	tissue	12.0
Smooth muscle	tissue	11.9	not detected
Esophagus	tissue	11.6	medium
Pancreas	tissue	10.8	medium
Spleen	tissue	10.8	medium
Thymus	tissue	10.5
Skin 1	tissue	10.4	medium
Locus coeruleus	tissue	10.0
Rectum	tissue	9.9	medium
Pituitary gland	tissue	9.8
Heart muscle	tissue	9.7	medium
Adrenal gland	tissue	9.7	high
Stomach 1	tissue	9.6	medium
Skeletal muscle	tissue	9.6	not detected
Tonsil	tissue	9.6	medium
Tongue	tissue	9.4
Lymph node	tissue	8.5	low
Placenta	tissue	7.7	medium
Kidney	tissue	7.6	medium
Breast	tissue	7.4	low
Hippocampus	tissue	7.3	low
Cerebellum	tissue	7.2	medium
Gallbladder	tissue	7.2	medium
Parathyroid gland	tissue	6.7	not detected
Nucleus accumbens	tissue	6.5
Cervix	tissue	6.4	medium
Seminal vesicle	tissue	6.3	medium
Cerebral cortex	tissue	5.5	medium
Postcentral gyrus	tissue	5.5
Somatosensory cortex	tissue	5.5
Corpus callosum	tissue	5.4
Olfactory bulb	tissue	5.2
Occipital cortex	tissue	5.2
Motor cortex	tissue	5.1
Basal ganglia	tissue	5.0	low
Thalamus	tissue	5.0
Superior colliculi	tissue	5.0
Hippocampal formation	tissue	5.0
Entorhinal cortex	tissue	5.0
Retrosplenial and cingulate cortex	tissue	5.0
Retrosplenial cortex	tissue	5.0
Putamen	tissue	4.8
Ventral forebrain	tissue	4.8
Periaqueductal gray	tissue	4.8
Temporal cortex	tissue	4.8
Insular cortex	tissue	4.8

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Periaquaductal grey, lateral (19.7), Nucleus tractus solitarii (19.3), Anterior thalamic nucleus, ventral (16.3), Dorsolateral tegmental area (16.3), Blood vessel (15.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

Functional genomics

gnomAD constraint: pLI 0.0118, LOEUF 1.76, missense Z -1.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000395693 — one region, missense o/e 1.23.

Literature-anchored findings (GeneRIF, showing 39)

• Mutations can cause fatal cytochrome c oxidase deficiency. Affected myoblasts can be rescued in vitro by transduction of the normal SCO2 gene or by copper administration. (PMID:11751685)
• Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations. (PMID:11931660)
• One novel SCO2 mutation has been identified in a patient with hypertrophic cardiomyopathy. (PMID:12538779)
• SCO2 mutation is associated spinal muscular atrophy type I phenotype (PMID:14994243)
• SCO2 transfers copper to the CuA site at an early stage of COX assembly in mitochondria. (PMID:15229189)
• The consequences of SCO2 and SURF1 mutations suggest the existence of tissue-specific functional differences of these proteins that may serve different tissue-specific requirements for the regulation of COX biogenesis. (PMID:16083427)
• data suggest that both Cu(I) and Cu(II) binding are critical for normal Sco function. (PMID:16091356)
• findings show that p53 modulates the balance between the utilization of respiratory and glycolytic pathways; identifed Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect (PMID:16728594)
• 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)
• structural and metal binding features of human Cu(I)Sco2 are similar to the Sco1 homolog, although the dynamic properties and the conformational disorder are quite different when apo forms and the copper(I)-loaded forms of the two proteins are compared (PMID:17850752)
• report extends knowledge of the pathology of COX deficiency caused by mutations in the SCO2 gene (PMID:18254779)
• Spinal muscular atrophy has been associated with mtDNA depletion or with mutations in the cytochrome-c oxidase assembly gene (SCO2; OMIM 604377). (PMID:18332255)
• Mutations in the SCO2 gene are a cause of prenatal-onset hypertrophic cardiomyopathy. (PMID:18924171)
• SCO2 acts upstream of SCO1, and that it is indispensable for CO II synthesis. (PMID:19336478)
• observations confirm that mutations in the SCO2 gene are frequently associated with the neurogenic pattern of skeletal muscle involvement accompanied by mitochondrial abnormalities (PMID:19353431)
• Mutations of SCO2 gene should be considered as a possible cause of neurogenic skeletal muscle features (including SMA-like) in infants with encephalomyopathy even in the absence of heart involvement and COX deficit. (PMID:19879173)
• recombinant fusion L-Sco2 protein was successfully transduced into the mitochondria of primary fibroblasts derived from SCO2/COX deficient patient and facilitated recovery of COX activity (PMID:20193760)
• Results describe the tissue distribution of SCO1 and SCO2 in mouse and human tissues. (PMID:20864674)
• These results suggest that p53 can modulate the metabolic pathways via the proteins SCO2 and TIGAR in human breast cancer. (PMID:21820150)
• Analysis of the mtDNA revealed that COX deficiency is caused by high levels of mtDNA deletions which accumulate with age in alzheimer disease. (PMID:21925769)
• wild-type p53 gene silencing reduced the expression of synthesis of cytochrome c oxidase 2 (SCO2), an effector necessary for respiratory chain function (PMID:22120717)
• Exogenous addition of the SCO2 gene to hypoxic cancer cells and hypoxic tumors induces apoptosis. (PMID:23319048)
• Autosomal recessive mutations in SCO2 are known to be associated with COX deficiency recognized as fatal infantile cardio-encephalomyopathy (PMID:23364397)
• oroxylin A could increase protein and mRNA expression of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2), which are the key metabolic modulators regulated by p53. (PMID:23612020)
• Mutations in SCO2 are associated with autosomal-dominant high-grade myopia. (PMID:23643385)
• alpha-particle-induced bystander effect is regulated by p53 and its downstream SCO2 in the irradiated hepatoma cells (PMID:23786650)
• COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase. (PMID:24403053)
• mutation in LRPAP1 is associated with high myopia. Further studies are expected to evaluate the pathogenicity of the variants in CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2. (PMID:25525168)
• Letter/Case Report: SCO2 mutations resulting in Leigh disease revealed at autopsy. (PMID:25720770)
• Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies. (PMID:25959673)
• oncoprotein HBXIP enhances glucose metabolism reprogramming through suppressing SCO2 and PDHA1 in breast cancer (PMID:26309161)
• 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)
• oxidative stress-induced glycolysis-to-OXPHOS switch is mediated by synthesis of cytochrome c oxidase 2 (SCO2). These findings demonstrate p53-mediated OXPHOS function as a compensatory alteration in Fanconi anemia (FA)hematopoietic stem cells to ensure a functional but mildly impaired energy metabolism and suggest a cautious approach to manipulating p53 signaling in FA. (PMID:26676373)
• Geranylgeranoic acid increased the SCO2 gene expression, which might enhance aerobic respiration. (PMID:26700591)
• We identified one novel possibility of an extreme myopia-causing mutation in SCO2. No other disease-causing mutation was found in 101 extremely myopic Japanese patients, suggesting that SCO2 plays a limited role in Japanese extreme myopia. (PMID:27052445)
• In gastric cancer, the expression of SCO2 and COX were not shown to be associated with the regulatory role of p53, unlike TIGAR expression. Nevertheless, a significantly high recurrence rate was found in a patient group with high COX expression (PMID:27499152)
• High expression of synthesis of cytochrome c oxidase 2 and TP53-induced glycolysis and apoptosis regulator can predict poor prognosis in human lung adenocarcinoma (PMID:29634976)
• Systemic Mitochondrial Oxidative Phosphorylation Protein Levels Correlate with Neuroimaging Measures in Chronically HIV-Infected Individuals. (PMID:31617381)
• TCF19 and p53 regulate transcription of TIGAR and SCO2 in HCC for mitochondrial energy metabolism and stress adaptation. (PMID:34369624)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	sco2	ENSDARG00000045555
mus_musculus	Sco2	ENSMUSG00000091780

Paralogs (1): SCO1 (ENSG00000133028)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3818630) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
muscle weakness	1
abnormal locomotor behavior	1
abnormal embryonic tissue morphology	1
increased liver copper level	1
abnormal copper level	1
abnormal mitochondrial ATP synthesis coupled electron transport	1
embryonic lethality between implantation and placentation, complete penetrance	1
impaired exercise endurance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Rickettsia conorii str. Malish 7	Q92H76	96.6%	Diamond
Rickettsia felis Marseille-URRWFXCal2	Q4UKW2	96.1%	Diamond
Rickettsia typhi str. Wilmington	Q68WF1	87.2%	Diamond
Rickettsia prowazekii str. Madrid E	Q9ZCW7	87.2%	Diamond
Bos taurus	A6H784	84.2%	Diamond
Rickettsia bellii RML369-C	Q1RIN4	81.4%	Diamond
Saccharomyces cerevisiae S288C	P23833	59.3%	Diamond
Schizosaccharomyces pombe 972h-	O42899	51.1%	Diamond
Arabidopsis thaliana	Q8VYP0	48.5%	Diamond
Rhodobacter capsulatus SB 1003	Q52720	42.4%	Diamond
Stutzerimonas stutzeri	P47206	38.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KLHDC7B-DT	ncRNA	105373098
KLHDC7B	protein-coding	113730
TYMP	protein-coding	1890
CIMAP1B	protein-coding	440836
SYCE3	protein-coding	644186
LINC03232	ncRNA	102724608
CPT1B	protein-coding	1375
CHKB-CPT1B	ncRNA	386593
NCAPH2	protein-coding	29781
MIOX	protein-coding	55586
LMF2	protein-coding	91289
ADM2	protein-coding	79924
SBF1	protein-coding	6305
PPP6R2	protein-coding	9701

Protein

Protein identifiers

Cytochrome c oxidase assembly factor SCO2 — O43819 (reviewed: O43819)

All UniProt accessions (2): A0A1W2PQK0, O43819

UniProt curated annotations — full annotation on UniProt →

Function. Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2); together with SCO1, facilitates the incorporation of copper into the Cu(A) site of MT-CO2/COX2. Could also act as a thiol-disulfide oxidoreductase to regulate the redox state of the cysteines in SCO1 during maturation of MT-CO2/COX2.

Subunit / interactions. Homodimer. Interacts with COA6. Found in a complex with TMEM177, COX20, COA6, MT-CO2/COX2, COX18 and SCO1. 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. Ubiquitous.

Disease relevance. Mitochondrial complex IV deficiency, nuclear type 2 (MC4DN2) [MIM:604377] An autosomal recessive, severe mitochondrial disorder characterized by hypotonia, global developmental delay, hypertrophic cardiomyopathy, lactic acidosis, gliosis, and neuronal loss in basal ganglia, brainstem and spinal cord. Serum lactate is increased, and laboratory studies show decreased mitochondrial complex IV protein and activity levels in various tissues, including heart and skeletal muscle. Most patients die in infancy of cardiorespiratory failure. The disease is caused by variants affecting the gene represented in this entry. Myopia 6 (MYP6) [MIM:608908] A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SCO1/2 family.

RefSeq proteins (4): NP_001162580, NP_001162581, NP_001162582, NP_005129* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003782	SCO1/SenC	Family
IPR013766	Thioredoxin_domain	Domain
IPR017276	Synth_of_cyt-c-oxidase_Sco1/2	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF02630

UniProt features (34 total): sequence variant 11, strand 8, helix 4, binding site 3, topological domain 2, transit peptide 1, chain 1, turn 1, transmembrane region 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2RLI	Solution structure of Cu(I) human Sco2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43819-F1	84.14	0.64

Human Protein Atlas

Protein class: Predicted membrane proteins, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH uncertain · IF supported

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)

Position	Role
133	Cu cation
137	Cu cation
224	Cu cation

Disulfide bonds (1)

Type	Positions
Redox-active	133–137

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

ID	Pathway	Evidence
R-HSA-9864848	Complex IV assembly	curated
R-HSA-5628897	TP53 Regulates Metabolic Genes	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-1430728	Metabolism	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-611105	Respiratory electron transport	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 424 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MCLACHLAN_DENTAL_CARIES_UP, GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, MODULE_45, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, MODULE_66, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, RICKMAN_METASTASIS_DN, ONKEN_UVEAL_MELANOMA_UP, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ELECTRON_TRANSPORT_CHAIN, GOCC_MITOCHONDRIAL_ENVELOPE, MODULE_88

GO Biological Process (5): eye development (GO:0001654), intracellular copper ion homeostasis (GO:0006878), mitochondrial respiratory chain complex IV assembly (GO:0033617), respiratory chain complex IV assembly (GO:0008535), cytochrome complex assembly (GO:0017004)

GO Molecular Function (5): copper ion binding (GO:0005507), protein-disulfide reductase activity (GO:0015035), copper chaperone activity (GO:0016531), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), myofibril (GO:0030016)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Transcriptional Regulation by TP53	1
Respiratory electron transport	1
Metabolism	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Aerobic respiration and respiratory electron transport	1
Gene expression (Transcription)	1

GO top-level categories

21 GO namespaces:

Category	Terms
sensory organ development	1
visual system development	1
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
protein-containing complex assembly	1
transition metal ion binding	1
disulfide oxidoreductase activity	1
catalytic activity, acting on a protein	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
eye development	BP	mutant phenotype
mitochondrial respiratory chain complex IV assembly	BP	mutant phenotype
mitochondrial inner membrane	CC	direct assay
mitochondrion	CC	direct assay
myofibril	CC	direct assay
protein-disulfide reductase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,600 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCO2	SURF1	Q15526	933
SCO2	COX17	Q14061	930
SCO2	COX10	Q12887	919
SCO2	COX15	Q7KZN9	910
SCO2	MT-CO2	P00403	833
SCO2	ATOX1	O00244	806
SCO2	COX11	Q9Y6N1	789
SCO2	TIGAR	Q9NQ88	770
SCO2	TACO1	Q9BSH4	742
SCO2	MT-CO1	P00395	736
SCO2	COX4I1	P13073	733
SCO2	COA6	Q5JTJ3	732
SCO2	MT-CO3	P00414	706
SCO2	COX6B1	P14854	706
SCO2	TP53	P04637	680

IntAct

Human interaction partners of SCO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
CIDEB	physical association	0.560	3
COX17	direct interaction	0.440	1
EPHA5	association	0.350	1
NDUFB8	association	0.350	1
STK33	association	0.350	1
MAP3K3	physical association	0.000	1

BioGRID (152 interactions; top human partners by supporting records): AIFM1 (Proximity Label-MS; 3 records), ANKRD11 (Cross-Linking-MS (XL-MS); 2 records), ARMC6 (Affinity Capture-MS; 2 records), CIDEB (Two-hybrid; 2 records), CUL3 (Affinity Capture-MS; 2 records), EYA4 (Affinity Capture-MS; 2 records), MET (Affinity Capture-MS; 2 records), MTMR14 (Affinity Capture-MS; 2 records), SCO1 (Proximity Label-MS; 2 records), APP (Reconstituted Complex), ATG14 (Affinity Capture-MS), ATP6V1E1 (Co-fractionation), AURKA (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
TP53	“up-regulates quantity by expression”	SCO2	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for SCO2: 87 ClinVar records (10 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	30
Likely benign	30
Benign	3

Top pathogenic / likely-pathogenic (10)

Showing all 10 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2735939	NM_005138.3(SCO2):c.116_131dup (p.Glu45fs)	Pathogenic	criteria provided, single submitter	1
2780143	NM_005138.3(SCO2):c.172C>T (p.Arg58Ter)	Pathogenic	criteria provided, single submitter	1
1325042	NM_005138.3(SCO2):c.224G>A (p.Trp75Ter)	Likely pathogenic	criteria provided, single submitter	1
3240429	NM_005138.3(SCO2):c.563del (p.Leu188fs)	Likely pathogenic	criteria provided, single submitter	1
3588119	NM_005138.3(SCO2):c.738_750dup (p.Ser251delinsGlyTer)	Likely pathogenic	criteria provided, single submitter	1
3588121	NM_005138.3(SCO2):c.210_229del (p.Leu71fs)	Likely pathogenic	criteria provided, single submitter	1
3588122	NM_001953.5(TYMP):c.1447T>C (p.Ter483Gln)	Likely pathogenic	criteria provided, single submitter	1
831985	NC_000022.11:g.(?50525760)(50529719_?)del	Pathogenic	criteria provided, single submitter	1
5683	NM_005138.3(SCO2):c.179_188dup (p.Ile63fs)	Pathogenic	no assertion criteria provided	1
5684	NM_005138.3(SCO2):c.398G>A (p.Cys133Tyr)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore SCO2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 338):

Position(s)	Effect	Δscore	Sites
22:50525470–50525471	donor_loss	0.9700	5
22:50524425–50524426	acceptor_loss	0.9300	6
22:50525015	donor_gain	0.9300
22:50525281	donor_gain	0.9200
22:50525470	donor_loss	0.9200
22:50525448	donor_gain	0.8900
22:50524433	acceptor_loss	0.8700
22:50525050	donor_gain	0.8600
22:50525531	donor_gain	0.8400
22:50524427	acceptor_loss	0.8300

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000911

Disease associations

OMIM: gene MIM:604272 | disease phenotypes: MIM:604377, MIM:608908, MIM:603041

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
Leigh syndrome	Definitive	Autosomal recessive
cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1	Definitive	Autosomal recessive	3
myopia 6	Strong	Autosomal dominant	2
Charcot-Marie-Tooth disease	Moderate	Autosomal recessive
autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

3 validity classifications:

Disease	Classification	Inheritance
Leigh syndrome	Definitive	AR
mitochondrial disease	Definitive	AR
Charcot-Marie-Tooth disease	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (17 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

17 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Hereditary neuropathy or pain disorder	green
Hypotonic infant	green
Inherited white matter disorders	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorder with complex IV deficiency	green
Mitochondrial disorders	green
Paediatric or syndromic cardiomyopathy	green
Possible mitochondrial disorder, nuclear genes	green
Undiagnosed metabolic disorders	green
White matter disorders and cerebral calcification - childhood onset	green
Early onset or syndromic epilepsy	amber
Paediatric disorders	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (6): cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (MONDO:0011451), myopia 6 (MONDO:0012154), mitochondrial DNA depletion syndrome 1 (MONDO:0011283), Leigh syndrome (MONDO:0009723), Charcot-Marie-Tooth disease (MONDO:0015626), autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect (MONDO:0033850)

Orphanet (2): Fatal infantile cytochrome C oxidase deficiency (Orphanet:1561), Mitochondrial neurogastrointestinal encephalomyopathy (Orphanet:298)

HPO phenotypes

showing 60 of 170 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000124	Renal tubular dysfunction
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000308	Microretrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000577	Exotropia
HP:0000580	Pigmentary retinopathy
HP:0000597	Ophthalmoparesis
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000741	Apathy
HP:0000750	Delayed speech and language development
HP:0000952	Jaundice
HP:0001098	Abnormal fundus morphology
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001276	Hypertonia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001310	Dysmetria
HP:0001324	Muscle weakness
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001348	Brisk reflexes
HP:0001349	Facial diplegia
HP:0001410	Decreased liver function
HP:0001427	Mitochondrial inheritance
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001605	Vocal cord paralysis
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001662	Bradycardia
HP:0001667	Right ventricular hypertrophy
HP:0001695	Cardiac arrest
HP:0001761	Pes cavus

GWAS associations

9 associations:

Study	Trait	p-value
GCST012020_238	Serum metabolite levels	4e-82
GCST90002404_191	Red cell distribution width	3e-33
GCST001765_11	Red blood cell traits	5e-23
GCST90002392_730	Mean corpuscular volume	4e-12
GCST90002390_77	Mean corpuscular hemoglobin	3e-11
GCST004146_29	Chronic lymphocytic leukemia	3e-9
GCST004608_195	Granulocyte percentage of myeloid white cells	7e-9
GCST001198_16	Multiple sclerosis	2e-8
GCST000587_8	Mean corpuscular hemoglobin	4e-8

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0009188	Red cell distribution width

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
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
C536105	Myopia 6 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067029 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11479	SCO2, TYMP	3	5.50	1	capecitabine;fluorouracil

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Copper	affects abundance, affects oxidation, decreases abundance	2
Reactive Oxygen Species	affects cotreatment, increases abundance, increases expression, increases phosphorylation, increases stability (+1 more)	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
cupric chloride	increases activity, increases reaction	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Bezafibrate	increases activity, increases reaction	1
Ethyl Methanesulfonate	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Paraquat	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652395	Binding	Binding affinity to human SCO2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 79 trials:

NCT	Phase	Status	Title
NCT04762758	Phase 3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT01721733	Phase 2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	Phase 2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	Phase 2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	Phase 2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	Phase 2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT00271635	Phase 2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	Phase 2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	Phase 2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	Phase 2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	Phase 2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	Phase 2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	Phase 2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	Phase 2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	Phase 2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT02171104	Phase 2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02544217	Phase 1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT02427178	Phase 1	WITHDRAWN	MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
NCT04378075	Phase 2/3	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
NCT01289704	Phase 2/3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT00541164	Phase 1/2	COMPLETED	Effects of Coenzyme Q10 on Charcot-Marie-Tooth Disease
NCT05361031	Phase 1/2	COMPLETED	The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
NCT07223632	Phase 1/2	ACTIVE_NOT_RECRUITING	Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient
NCT00149045	Not specified	COMPLETED	Follow up and Observation of Charcot Marie Tooth Disease in Families
NCT01193075	Not specified	RECRUITING	Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others
NCT01203085	Not specified	COMPLETED	Development of Charcot Marie Tooth Disease (CMT) Pediatric Scale for Children With CMT
NCT01455623	Not specified	COMPLETED	Development and Validation of a Disability Severity Index for CMT
NCT01918826	Not specified	COMPLETED	Evaluation of the Analgesic Efficiency of the Transcutaneous Neurostimulation in the Charcot Syndrome Marie Tooth on the Pains of Lower Limbs
NCT02001038	Not specified	COMPLETED	Survey of Current Management of Orthopaedic Complications in CMT Patients
NCT02011204	Not specified	COMPLETED	Study of Electrical Impedance Myography (EIM) in ALS
NCT02194010	Not specified	COMPLETED	Disability Severity Scale (DSI) and Hereditary Motor and Sensory Neuropathy Overall Disability Scale (HMSN-R-ODS)
NCT02429947	Not specified	COMPLETED	An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients
NCT02532244	Not specified	COMPLETED	Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02788734	Not specified	COMPLETED	Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies
NCT02979145	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Infant Scale (INC-6611)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03460951	Not specified	COMPLETED	Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy (PIDC)
NCT03715283	Not specified	COMPLETED	Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care
NCT03782883	Not specified	COMPLETED	The Impact of Charcot-Marie-Tooth Disease in the Real World
NCT03810508	Not specified	TERMINATED	A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
NCT03966287	Not specified	COMPLETED	Analysis of Pain and Quality of Life in Patients With Charcot-Marie-Tooth Neuropathy (CMT)
NCT04010188	Not specified	RECRUITING	A Registered Cohort Study on Charcot-Marie-Tooth Disease
NCT04283175	Not specified	COMPLETED	Validation Study of Posturology Platforms for Evaluating Postural Control of Hemiparetic and Neuro-muscular Patients
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT04786522	Not specified	COMPLETED	Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
NCT04967716	Not specified	UNKNOWN	Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases
NCT04980807	Not specified	COMPLETED	Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls
NCT05011006	Not specified	TERMINATED	NT-3 Levels and Function in Individuals With CMT
NCT05827419	Not specified	TERMINATED	Hearing and Balance Disorders in Peripheral Neuropathy
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT06203093	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Biological Sample Collection for IPSC Generation and Biobanking
NCT06666816	Not specified	RECRUITING	Observational Study to Observe Variations of Gait Parameters in Patients With Neuromuscular Diseases

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SCO2 across ~30M SureChEMBL compounds — explore on Sugi Predict.