COX17

Chr 3

cytochrome c oxidase copper chaperone COX17

Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein which is not a structural subunit, but may be involved in the recruitment of copper to mitochondria for incorporation into the COX apoenzyme. This protein shares 92% amino acid sequence identity with mouse and rat Cox17 proteins. This gene is no longer considered to be a candidate gene for COX deficiency. A pseudogene COX17P has been found on chromosome 13. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
GOFmechanismLOEUF 1.54
Clinical SummaryCOX17
Population Constraint (gnomAD)
Low constraint (pLI 0.20) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
8 VUS of 9 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.54LOEUF
pLI 0.199
Z-score 0.98
OE 0.36 (0.131.54)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.23Z-score
OE missense 0.89 (0.671.20)
32 obs / 35.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.36 (0.131.54)
00.351.4
Missense OE?0.89 (0.671.20)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 1 / 2.8Missense obs/exp: 32 / 35.9Syn Z: -0.08

This gene — mechanism propensity

DN
0.6164th %ile
GOF
0.6736th %ile
LOF
0.2581th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

9 submitted variants in ClinVar

Classification Summary

VUS8
8
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
8
0
0
8
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total08008

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap COX17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

COX17 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →