SCO1

Chr 17AR

synthesis of cytochrome C oxidase 1

Also known as: MC4DN4, SCOD1

NCBI Gene: 6341 ENSG00000133028 OMIM: 603644

The protein functions as a copper metallochaperone essential for assembly of cytochrome c oxidase (complex IV) by facilitating incorporation of subunits 1 and 2 into the holoenzyme within the mitochondrial inner membrane. Mutations cause mitochondrial complex IV deficiency with autosomal recessive inheritance through a predicted dominant-negative mechanism. The low pLI score indicates tolerance to heterozygous loss-of-function variants, consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.991 OMIM phenotype

Clinical Summary— SCO1

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.59

OE 0.55 (0.32–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.20Z-score

OE missense 1.04 (0.92–1.18)

177 obs / 169.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.32–0.99)

0≤0.351.4

Missense OE?1.04 (0.92–1.18)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 8 / 14.6Missense obs/exp: 177 / 169.8Syn Z: -0.54

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSCO1-related mitochondrial complex IV deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.6053th %ile

LOF

0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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