MT-ATP8

mitochondrially encoded ATP synthase membrane subunit 8, the group of Mitochondrially encoded protein coding genes|Mitochondrial complex V: ATP synthase subunits

Basic information

Region (hg38): M:8366-8572

Previous symbols: [ "MTATP8" ]

Links

ENSG00000228253 ∙ NCBI:4509 ∙ OMIM:516070 ∙ HGNC:7415 ∙ Uniprot:P03928 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial proton-transporting ATP synthase complex deficiency (Supportive), mode of inheritance: AR
• periodic paralysis with later-onset distal motor neuropathy (Supportive), mode of inheritance: Mitochondrial
• mitochondrial disease (Limited), mode of inheritance: AR
• mitochondrial disease (Limited), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brain pseudoatrophy, reversible, valproate-induced, susceptibility to	Maternal	Pharmacogenomic	Medication selection would be impacted in individuals with variants	Biochemical; Cardiovascular; Neurologic	17101920; 17954552; 19188198
Variants can also be associated with a range of typical mitochondrial-related phenotypes, including cardiac manifestations such as cardiomyopathy

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MT-ATP8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ATP8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	0	0	0

Variants in MT-ATP8

This is a list of pathogenic ClinVar variants found in the MT-ATP8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
M-8369-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8373-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8373-A-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8379-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8381-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-8381-A-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8382-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8387-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-8387-G-T			Uncertain significance (Oct 06, 2023)
M-8388-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-8393-C-T		Brain pseudoatrophy, reversible, valproate-induced, susceptibility to • Leigh syndrome	Benign (Oct 17, 2019)
M-8394-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8396-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-8397-C-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8400-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-8403-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8406-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-8408-C-T		See cases	Uncertain significance (Nov 02, 2018)
M-8410-C-T			Likely benign (Mar 18, 2016)
M-8411-A-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8411-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8412-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8414-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-8415-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8417-C-T		Leigh syndrome	Benign (Oct 17, 2019)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane (By similarity). {ECO:0000250}.
• Disease: DISEASE: Mitochondrial complex V deficiency, mitochondrial 2 (MC5DM2) [MIM:516070]: A mitochondrial disorder with heterogeneous clinical manifestations including neuropathy, ataxia, hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy can present with negligible to extreme hypertrophy, minimal to extensive fibrosis and myocyte disarray, absent to severe left ventricular outflow tract obstruction, and distinct septal contours/morphologies with extremely varying clinical course. {ECO:0000269|PubMed:19188198}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, infantile hypertrophic (CMHI) [MIM:500006]: An infantile form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:19188198}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
• Pathway: Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;Formation of ATP by chemiosmotic coupling;The citric acid (TCA) cycle and respiratory electron transport;Purine metabolism;Metabolism;Cristae formation;Mitochondrial biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.;Organelle biogenesis and maintenance (Consensus)

Haploinsufficiency Scores

• pHI: 0.159

Mouse Genome Informatics

• Gene name: mt-Atp8
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: ATP biosynthetic process;cristae formation;mitochondrial ATP synthesis coupled proton transport
• Cellular component: mitochondrial proton-transporting ATP synthase complex, coupling factor F(o);mitochondrial inner membrane;mitochondrial proton-transporting ATP synthase complex;integral component of membrane
• Molecular function: proton transmembrane transporter activity;ATPase activity;transmembrane transporter activity