COX19

Chr 7

cytochrome c oxidase assembly factor COX19

NCBI Gene: 90639 ENSG00000240230 UniProt: Q49B96

COX19 encodes an assembly factor for cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) that acts as a COX11 chaperone supporting copper coordination and stimulates copper delivery to COX1 and COX2. Mutations cause mitochondrial complex IV deficiency, an autosomal recessive disorder typically presenting in infancy or early childhood with neurodegeneration, developmental delay, and multi-organ dysfunction. The gene shows low constraint to loss-of-function variation, consistent with recessive inheritance patterns.

ResearchSummary from RefSeq, UniProt

COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.91

Clinical Summary— COX19

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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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ClinVar Variants

14 VUS of 19 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.004

Z-score -0.37

OE 1.26 (0.51–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.02Z-score

OE missense 1.44 (1.17–1.77)

62 obs / 43.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.26 (0.51–1.91)

0≤0.351.4

Missense OE?1.44 (1.17–1.77)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 3 / 2.4Missense obs/exp: 62 / 43.1Syn Z: -1.04

This gene — mechanism propensity

0.81top 10%

GOF

0.5856th %ile

LOF

0.2191th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

19 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	14	14
Likely Benign	2	2
Benign	0	0
Total	16	16

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

40 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap COX19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →