Mitochondrial disorder with complex V deficiency

Gene: ATP5G3

Green List (high evidence)

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

Created: 1 Feb 2023, 12:09 p.m. | Last Modified: 1 Feb 2023, 12:09 p.m.

Panel Version: 1.17

Green List (high evidence)

Gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) in August 2022 on behalf of the three GMS Mitochondrial providers, indicating that this gene requires a rating upgrade from Amber to Green.

Created: 30 Aug 2022, 9:10 a.m. | Last Modified: 30 Aug 2022, 9:10 a.m.

Panel Version: 1.10

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels

Created: 25 Aug 2022, 9:45 a.m. | Last Modified: 25 Aug 2022, 9:45 a.m.

Panel Version: 1.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681

Publications

• 34636445
• 34954817

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: no reports of human disease; complex V subunit

Created: 10 May 2019, 12:10 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Publications

• none found

Green List (high evidence)

ATP5G3 has a new gene name: ATP5MC3

Created: 4 Feb 2019, 11:55 a.m.

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. Gene Symbol submitted: ATP5MC3; Suggested intial gene rating: Green.

Created: 4 Feb 2019, 10:48 a.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Added new-gene-name tag, new approved HGNC gene symbol is ATP5MC3

Created: 21 Mar 2018, 1:03 p.m.

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, 12:38 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 1.132) - further evidence needs to be submitted to support promoting this gene family member to Green.

Created: 29 Mar 2019, 1:14 p.m.

Comment when marking as ready: Candidate gene - kept in red list.

Created: 26 Feb 2016, 1:35 p.m.

I don't know

no mutation reports in literature;
good candidate gene for mitochondrial complex V (ATP synthase) deficiency

Created: 3 Feb 2016, 6:04 p.m.