COX17

Chr 3

cytochrome c oxidase copper chaperone COX17

NCBI Gene: 10063 ENSG00000138495 UniProt: Q14061 OMIM: 604813

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.199

Z-score 0.98

OE 0.36 (0.13–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.23Z-score

OE missense 0.89 (0.67–1.20)

32 obs / 35.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.13–1.54)

0≤0.351.4

Missense OE?0.89 (0.67–1.20)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 1 / 2.8Missense obs/exp: 32 / 35.9Syn Z: -0.08

Background carrier burden — how many people carry a rare variant somewhere in COX17?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 680

122 rare PASS variants

Rare truncating (LoF)

1 in 1,700

23 rare PASS variants

Rare synonymous (reference)

1 in 1,400

44 rare PASS variants

Rare missense and truncating variants are carried at similar rates in COX17; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 820	1 in 5,300
South Asian	~43k	1 in 280	1 in 3,200
Remaining (unassigned)	~30k	1 in 950	1 in 670
European (Finnish)	~27k	≈ 1 in 7,400	≈ 1 in 17,000
Admixed American	~22k	1 in 860	1 in 1,900
African / African American	~21k	1 in 700	≈ 1 in 6,800
East Asian	~20k	1 in 2,000	1 in 890
Ashkenazi Jewish	~13k	≈ 1 in 3,000	≈ 1 in 10,000
Middle Eastern	~2,869	≈ 1 in 750	≈ 1 in 2,000

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓