COX7C

Chr 5

cytochrome c oxidase subunit 7C

NCBI Gene: 1350 ENSG00000127184 UniProt: P15954

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 subunit VIIc, which shares 87% and 85% amino acid sequence identity with mouse and bovine COX VIIc, respectively, and is found in all tissues. A pseudogene COX7CP1 has been found on chromosome 13. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.14LOEUF

pLI 0.564

Z-score 1.47

OE 0.00 (0.00–1.14)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.33Z-score

OE missense 0.84 (0.61–1.15)

27 obs / 32.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.14)

0≤0.351.4

Missense OE?0.84 (0.61–1.15)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 0 / 2.5Missense obs/exp: 27 / 32.3Syn Z: -0.75

Background carrier burden — how many people carry a rare variant somewhere in COX7C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 2,600

59 rare PASS variants

Rare truncating (LoF)

1 in 6,100

15 rare PASS variants

Rare synonymous (reference)

1 in 640

26 rare PASS variants

Rare missense and truncating variants are carried at similar rates in COX7C; 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 2,400	1 in 6,200
South Asian	~43k	1 in 4,100	≈ 1 in 17,000
Remaining (unassigned)	~30k	1 in 3,800	1 in 3,800
European (Finnish)	~27k	≈ 1 in 13,000	≈ 1 in 27,000
Admixed American	~22k	1 in 3,800	1 in 1,400
African / African American	~21k	≈ 1 in 4,200	≈ 1 in 9,200
East Asian	~20k	1 in 1,500	none seen
Ashkenazi Jewish	~13k	≈ 1 in 2,600	none seen
Middle Eastern	~2,883	≈ 1 in 2,900	none seen

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 ↓