Likely inborn error of metabolism

Gene: ATP5A1

Green List (high evidence)

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

Green List (high evidence)

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). Two families (with two affected sibs each) reported with recessive variants and supported by functional studies (PMIDs: 23599390; 23596069). Six unrelated patients have been reported with heterozygous variants; including one recurrent variant c.620G>A in four cases, c.545G>A and c.1037C>T in the remaining two, respectively (PMIDs: 34483339; 34954817). The MOI has been updated from biallelic to both mono- and biallelic inline with published cases. Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.

Created: 30 Aug 2022, 9:08 a.m. | Last Modified: 30 Aug 2022, 9:08 a.m.

Panel Version: 2.265

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4, OMIM: 615228; Combined oxidative phosphorylation deficiency 22, OMIM: 616045

Publications

• 34483339
• 23596069
• 23599390
• 34954817

Added new-gene-name tag, new approved HGNC gene symbol for ATP5A1 is ATP5F1A

Created: 9 May 2019, 2:59 p.m.

Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys mentioned in this article have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.

Created: 22 Aug 2019, 10:01 a.m. | Last Modified: 27 Sep 2019, 3:07 p.m.

Panel Version: 1.311

Comment on list classification: No additional variants have been reported to date.

Created: 30 Apr 2019, 10:26 a.m.

Comment on publications: PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency);PMID: 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).

Created: 30 Apr 2019, 10:25 a.m.

Comment on list classification: Kept as red, as each phenotype association has only been reported in one family - as indicated by reviewer's comment.

Created: 26 Feb 2016, 12:40 p.m.

Green List (high evidence)

single report in literature - two affected siblings

Created: 3 Feb 2016, 6 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal