COA6

Chr 1AR

cytochrome c oxidase assembly factor 6

Also known as: C1orf31, CEMCOX4, MC4DN13

NCBI Gene: 388753 ENSG00000168275 UniProt: Q5JTJ3 OMIM: 614772

The protein functions as a cytochrome c oxidase assembly factor in the mitochondrial intermembrane space, facilitating proper assembly of mitochondrial respiratory complex IV. Mutations cause mitochondrial complex IV deficiency, nuclear type 13, which presents as fatal infantile cardiomyopathy and follows an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function effects.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 13MIM #616501

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.45

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — COA6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.45LOEUF

pLI 0.006

Z-score 0.81

OE 0.65 (0.32–1.45)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.72Z-score

OE missense 0.75 (0.60–0.95)

50 obs / 66.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.32–1.45)

0≤0.351.4

Missense OE?0.75 (0.60–0.95)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 4 / 6.2Missense obs/exp: 50 / 66.5Syn Z: -0.02

Background carrier burden — how many people carry a rare variant somewhere in COA6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

329 rare PASS variants

Rare truncating (LoF)

1 in 2,800

49 rare PASS variants

Rare synonymous (reference)

1 in 430

130 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COA6. 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 250	1 in 2,800
South Asian	~43k	1 in 200	1 in 6,000
Remaining (unassigned)	~30k	1 in 130	1 in 840
European (Finnish)	~27k	1 in 780	≈ 1 in 27,000
Admixed American	~22k	1 in 98	1 in 1,200
African / African American	~21k	1 in 230	≈ 1 in 6,400
East Asian	~20k	1 in 260	1 in 1,400
Ashkenazi Jewish	~13k	1 in 1,300	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 130	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): 2 of 3 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 3.? see exons ↓