Possible mitochondrial disorder - nuclear genes

Gene: COX5A

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 11:42 a.m. | Last Modified: 4 Dec 2024, 11:42 a.m.

Panel Version: 3.113

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

To date, two COX5A variants have been associated with Mitochondrial complex IV deficiency, nuclear type 20 (OMIM:619064) in two unrelated cases (PMID: 28247525;35246835). Analysis of patient fibroblasts has revealed a reduced enzymatic activity and protein levels of complex IV and several of its subunits, plus, lentiviral complementation rescues the complex IV deficiency (PMID: 28247525;35246835).

Created: 9 Jan 2024, 12:35 p.m. | Last Modified: 9 Jan 2024, 12:35 p.m.

Panel Version: 3.85

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 9 Jan 2024, 11:02 a.m. | Last Modified: 9 Jan 2024, 11:02 a.m.

Panel Version: 3.85

I don't know

Second family reported - one patient with a homozygous missense variant in COX5A

Created: 23 Aug 2023, 12:44 p.m. | Last Modified: 23 Aug 2023, 12:44 p.m.

Panel Version: 3.48

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Mitochondrial complex IV deficiency, nuclear type 20

Publications

• 35246835

I don't know

Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: One family (2 sibs) and functional studies

Created: 10 May 2019, 1:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
No OMIM phenotype

Publications

• 28247525

Green List (high evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.

Created: 4 Feb 2019, 1:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pulmonary arterial hypertension, lactic acidemia, and failure to thrive

Publications

• 28247525

Comment when marking as ready: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter.

Created: 10 May 2019, 1:31 p.m.

Comment on list classification: This gene has been demoted to Amber until further evidence is provided. This gene is currently Red on the Mitochondrial disorders panel (code 112, Version 1.151) - further evidence needs to be submitted to support promoting this gene family member to Green.

Created: 29 Mar 2019, 2:27 p.m.

Comment when marking as ready: Candidate gene therefore on the red list.

Created: 26 Feb 2016, 4:59 p.m.

I don't know

no mutation reports in literature;

good candidate gene for complex IV deficiency (encodes a subunit of the enzyme)

Created: 4 Feb 2016, 1:18 p.m.