SCO2

Chr 22ARAD

synthesis of cytochrome C oxidase 2

Also known as: CEMCOX1, ECGF1, Gliostatin, MC4DN2, MYP6, PD-ECGF, SCO1L, TP

SCO2 encodes a metallochaperone essential for the assembly of cytochrome c oxidase subunit II, which is required for mitochondrial complex IV function and aerobic ATP production. Mutations cause mitochondrial complex IV deficiency with fatal infantile encephalocardiomyopathy and myopia 6, inherited in autosomal recessive and autosomal dominant patterns. The pathogenic mechanism involves impaired cytochrome c oxidase assembly leading to defective mitochondrial respiratory chain function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 1.762 OMIM phenotypes
Clinical SummarySCO2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.76LOEUF
pLI 0.000
Z-score -0.21
OE 1.08 (0.651.76)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.61Z-score
OE missense 1.36 (1.221.52)
219 obs / 161.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.08 (0.651.76)
00.351.4
Missense OE1.36 (1.221.52)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 9 / 8.4Missense obs/exp: 219 / 161.4Syn Z: -1.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSCO2-related myopiaOTHERAD
definitiveSCO2-related fatal infantile cardioencephalomyopathy due to cytochrome c oxidase deficiencyLOFAR
DN
0.6550th %ile
GOF
0.6150th %ile
LOF
0.3549th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNOverexpression of either wild-type SCO protein in the reciprocal patient background resulted in a dominant-negative phenotype, suggesting a physical interaction between SCO1 and SCO2.PMID:15229189

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SCO2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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