Likely inborn error of metabolism - targeted testing not possible
Gene: ATP5G3
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 10:24 a.m. | Last Modified: 1 Feb 2023, 10:24 a.m.
Panel Version: 3.6
This gene was recently included on a gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) on behalf of GMS Mitochondrial providers, indicating that the rating should be upgraded from Amber to Green on Mitochondrial panels (R357 and R63). As there is sufficient supporting evidence, the rating should also be updated to Green on this panel at the next GMS review.Created: 30 Aug 2022, 9:08 a.m. | Last Modified: 30 Aug 2022, 9:08 a.m.
Panel Version: 2.265
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 levelsCreated: 25 Aug 2022, 9:45 a.m. | Last Modified: 25 Aug 2022, 9:45 a.m.
Panel Version: 2.264
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681
Publications
Added new-gene-name tag, new approved HGNC gene symbol for ATP5G3 is ATP5MC3Created: 9 May 2019, 3:08 p.m.
Comment when marking as ready: Candidate gene - kept in red list.Created: 26 Feb 2016, 1:35 p.m.
no mutation reports in literature;
good candidate gene for mitochondrial complex V (ATP synthase) deficiencyCreated: 3 Feb 2016, 6:04 p.m.
Tag Q3_22_rating was removed from gene: ATP5G3.
Source NHS GMS was added to ATP5G3. Source Expert Review Green was added to ATP5G3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: atp5g3 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: ATP5G3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to
Phenotypes for gene: ATP5G3 were changed from No OMIM phenotype to Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681
Tag Q3_22_rating tag was added to gene: ATP5G3.
Tag new-gene-name tag was added to gene: ATP5G3.
Sarah Leigh: Associated with phenotype in O
gene: ATP5G3 was added gene: ATP5G3 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: ATP5G3 was set to Unknown Phenotypes for gene: ATP5G3 were set to No OMIM phenotype