Possible mitochondrial disorder - nuclear genes

Gene: ATP5B

I don't know

In the opinion of Helen Brittain (Clinical Fellow, Genomics England) is "There is a lack of clarity over the penetrance, plus also the phenotypes are somewhat disparate (the twins had DD with episodic hyperthermia, whereas the other cases presented with dystonia). A gene:disease association cannot be made at this time".

Created: 23 Nov 2023, 4:46 p.m. | Last Modified: 23 Nov 2023, 4:46 p.m.

Panel Version: 3.68

PMIDs 36239646 & 36860166 report a total of three ATP5B (ATP5F1B) heterozygous variants in three unrelated families. The subjects described in PMID 36239646 were monozygotic twins with de novo variant NM_001686.3: c.1004 T>C, (p.Leu335Pro). They had congenital hypermetabolism and uncoupled oxidative phosphorylation. The affected members of the two families described by PMID 36860166 had early-onset isolated dystonia. The heterozygous ATP5B (ATP5F1B) variants (NM_001686.4: c.1000A>C; p.Thr334Pro & c.1445T>C; p.Val482Ala) were inherited, with a total of four affected individuals and three unaffected carriers (PMID 36860166 figure 1), thereby, it was stated that the condition had incomplete penetrance in these cases.

Created: 7 Nov 2023, 5:38 p.m. | Last Modified: 7 Nov 2023, 5:38 p.m.

Panel Version: 3.63

I don't know

De novo heterozygous missense mutation in a pair of monozygotic twin boys (PMID: 36239646). Functional studies done.

Two different variants recently reported in PMID: 36860166 in patients with early-onset isolated dystonia. One variant is at neighbouring amino acid to the one found above. Functional studies done. However, both variants also found in unaffected family members - incomplete penetrance suggested.

Created: 22 Aug 2023, 3:52 p.m. | Last Modified: 22 Aug 2023, 3:52 p.m.

Panel Version: 3.48

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2

Publications

• 36239646
• 36860166

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, 1:02 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Publications

• none found

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.

New gene symbol: ATP5F1B

Created: 4 Feb 2019, 12:55 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Added new-gene-name tag, new approved HGNC gene symbol is ATP5F1B

Created: 21 Mar 2018, 12:43 p.m.

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

Created: 10 May 2019, 1:05 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, 1:22 p.m.

Comment on list classification: Candidate gene therefore should remain on the red list.

Created: 26 Feb 2016, 12:42 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, 6:02 p.m.