Likely inborn error of metabolism

Gene: COX4I1

Green List (high evidence)

Comment on list classification: This gene should also be rated green on this panel as this has already been rated green on R356 Mitochondrial disorder with complex IV deficiency panel (https://panelapp.genomicsengland.co.uk/panels/537/gene/COX4I1/) and is being currently recommended for promotion to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/COX4I1/)

There are two unrelated cases and functional evidence in support of the association of this gene with Mitochondrial complex IV deficiency.

Created: 6 Jun 2025, 1:38 p.m. | Last Modified: 6 Jun 2025, 1:38 p.m.

Panel Version: 8.6

PMID:28766551 reported a 5-year-old girl identified with homozygous COX4I1 variant (p.(Lys101_Thr102delinsAsnSer)) and mitochondrial complex IV deficiency, which segregated with the disorder in the family.

PMID:31290619 reported two brothers of Iraqi descent, identified with a homozygous missense variant in the COX4I1 gene (p.(Pro152Thr)) and mitochondrial complex IV deficiency, which also segregated with the disorder in the family.

There is also functional evidence available from the above publications.

This gene is also associated with relevant phenotypes in OMIM (MIM #619060).

Created: 6 Jun 2025, 1:35 p.m. | Last Modified: 6 Jun 2025, 1:35 p.m.

Panel Version: 8.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex IV deficiency, nuclear type 16, OMIM:619060

Publications

• 28766551
• 31290619
• 33578848

Comment on list classification: Demoted to red as the evidence for this gene is uncertain.

Created: 8 Feb 2016, 11:27 a.m.

I don't know

no reports of mutations in literature

Created: 3 Feb 2016, 5:15 p.m.