MT-ATP8
protein-codingmitochondrially encoded ATP synthase membrane subunit 8, the group of Mitochondrially encoded protein coding genes|Mitochondrial complex V: ATP synthase subunits
Gene summary
Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in proton motive force-driven mitochondrial ATP synthesis. Located in mitochondrion. Part of proton-transporting ATP synthase complex. Implicated in multiple sclerosis and urinary bladder cancer. [provided by Alliance of Genome Resources, Jul 2025]
- MTATP8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~0.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0044970
Submitter: Illumina
Inheritance Pattern: AR
Disease ID:MONDO:0014471
Submitter: Orphanet
Inheritance Pattern: Mitochondrial
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *MT-ATP8* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of November 28, 2022. The *MT-ATP8* gene encodes the ATP synthase (complex V) subunit 8. Defects of this protein lead to complex V deficiency. The *MT-ATP8* gene was first reported in relation to maternally-inherited primary mitochondrial disease in 2010 (PMID: 20207608). There have been several additional reports linking variants in this gene to various phenotypes associated with primary mitochondrial disease, including before 2010, but there was insufficient evidence to conclude that the features seen in reported individuals were caused by the identified variants (PMIDs: 15452396, 11062027, 28027978, 23735083, 32858252). Over time, multisystem medical concerns have been reported in affected individuals, representing one disease entity according to the ClinGen Lumping and Splitting Framework. This phenotype is considered a primary mitochondrial disease. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included three variants (m.8403T>C, m.8411A>G, m.8424T>C) identified in three probands from three publications (PMIDs: 24153443, 20207608, 32858252). Age of onset varied from birth to the 30s. Features in affected individuals included muscle weakness, wasting, and cramping; dysarthria, headache, periodic paralysis, seizures, mood disorder, neuropathy, pancreatitis, diarrhea, and weight loss. Brain imaging revealed cerebellar atrophy and labs showed elevated lactate. The mechanism of disease appears to be loss of function. This 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 (PMIDs: 33340416, 32858252, 19759059, 22919063). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on November 28, 2022 (SOP Version 9). This gene-disease relationship was reevaluated on July 14, 2025 by this Expert Panel. As a result of this reevaluation, the classification did not change.
Inheritance Pattern: Mitochondrial
Disease ID:MONDO:0018343
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Cardiovascular; Neurologic
Intervention: Pharmacogenomic
Rationale: Medication selection would be impacted in individuals with variants
Comments: Variants can also be associated with a range of typical mitochondrial-related phenotypes, including cardiac manifestations such as cardiomyopathy
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MT-ATP8 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 0 | 0 | 0 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000355265.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- ATP biosynthetic process
- cristae formation
- mitochondrial ATP synthesis coupled proton transport
Molecular Function
- proton transmembrane transporter activity
- ATPase activity
- transmembrane transporter activity
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
dbNSFP Gene Annotations
Source:
- 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.;