Mitochondrial disorders

Gene: MT-ATP8

Green List (high evidence)

As reviewed by Zornitza Stark, there are 3 individuals reported with primary mitochondrial disease and variants in MT-ATP8. Hence, this gene should remain Green for Mitochondrial disorders.

This gene is not yet associated with a phenotype in OMIM (accessed 19th Dec 2025).

Created: 19 Dec 2025, 11:15 a.m. | Last Modified: 19 Dec 2025, 11:16 a.m.

Panel Version: 9.38

I don't know

LIMITED by ClinGen. Three variants (m.8403T>C, m.8411A>G, m.8424T>C) have been reported in three individuals. Age of onset varied from birth to the 30s. Clinical features included muscle weakness, wasting, and cramping; dysarthria, headache, periodic paralysis, seizures, mood disorder, neuropathy, pancreatitis, diarrhoea, and weight loss. Brain imaging revealed cerebellar atrophy; lactate was elevated. The gene-disease relationship is also supported by a biochemical function (complex V subunit) shared with other genes associated with primary mitochondrial disease, functional alteration in non-patient cells, and model organisms.

Created: 3 Dec 2025, 7:31 a.m. | Last Modified: 3 Dec 2025, 7:31 a.m.

Panel Version: 9.36

Mode of inheritance
MITOCHONDRIAL

Phenotypes
Mitochondrial cardiomyopathy complex V (ATP synthase) deficiency

Publications

• 24153443
• 20207608
• 32858252
• 33340416
• 32858252
• 19759059
• 22919063

Comments from Dr Atsuko Okazaki (Division of Genomic Medicine Research, Medical Genomics Center, National Center for Global Health and Medicine, Tokyo, Japan): "Among variants in an overlapping region of MT-ATP6/8, m.8528T>C is reported as a confirmed mutation for infantile hypertrophic cardiomyopathy (Ware SM et al, Journal of Medical Genetics, 2009, Imai et al, Journal of International Cardiology, 2016".

Created: 5 Oct 2020, 1:28 p.m. | Last Modified: 5 Oct 2020, 1:28 p.m.

Panel Version: 2.8

Green List (high evidence)

Mode of inheritance
MITOCHONDRIAL

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

Comments from Dr Atsuko Okazaki (Division of Genomic Medicine Research, Medical Genomics Center, National Center for Global Health and Medicine, Tokyo, Japan): "Only m.8528T>C (to be exact, it is an overlapping region of MT-ATP6/ATP8) can be reported as a confirmed mutation for infantile hypertrophic cardiomyopathy. In comparison, m.8527A>G is a polymorphism for MT-ATP8 and possibly disease-associated for MT-ATP6 (amber/red) although both m.8527A>G and m.8528T>C are located in MT-ATP8 gene."

Created: 4 Dec 2018, 11:25 a.m.

Comment on list classification: Both reviewers agree this gene should be promoted from red to green.

Created: 10 Feb 2016, 12:40 p.m.

Green List (high evidence)