MT-ATP6

mitochondrially encoded ATP synthase membrane subunit 6, the group of Mitochondrial complex V: ATP synthase subunits|Mitochondrially encoded protein coding genes

Basic information

Region (hg38): M:8527-9207

Previous symbols: [ "MTATP6", "RP" ]

Links

ENSG00000198899 ∙ NCBI:4508 ∙ OMIM:516060 ∙ HGNC:7414 ∙ Uniprot:P00846 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
• NARP syndrome (Supportive), mode of inheritance: Mitochondrial
• familial infantile bilateral striatal necrosis (Supportive), mode of inheritance: AD
• mitochondrial proton-transporting ATP synthase complex deficiency (Supportive), mode of inheritance: AR
• maternally-inherited Leigh syndrome (Supportive), mode of inheritance: Mitochondrial
• maternally-inherited spastic paraplegia (Supportive), mode of inheritance: Mitochondrial
• periodic paralysis with later-onset distal motor neuropathy (Supportive), mode of inheritance: Mitochondrial
• NARP syndrome (Definitive), mode of inheritance: Mitochondrial
• mitochondrial disease (Definitive), mode of inheritance: Mitochondrial
• Leigh syndrome (Definitive), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, lactic acidosis, and sideroblastic anemia 3	Maternal	Cardiovascular; Hematologic	Among other manifestations, the conditions can involve transfusion-dependent anemia, and awareness may allow early management; Surveillance for cardiovascular manifestations may allow early medical interventions	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	2137962; 1436530; 1550128; 8095070; 8250532; 8042671; 8554662; 7726182; 7668837; 8739943; 9199572; 9329425; 9501263; 9631394; 9556461; 10417290; 10590437; 10604142; 10676807; 11245730; 11730668; 11843698; 17452590; 19124644; 19188198; 22231385; 22577227; 22773856; 25037980
In many of the allelic disorders, mtochondrial variants may involve a variety of sequelae, including cardiovascular manifestations such as cardiomyopathy

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MT-ATP6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-ATP6 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-ATP6

This is a list of pathogenic ClinVar variants found in the MT-ATP6 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-8528-T-C		Cardiomyopathy, infantile hypertrophic • Histiocytoid cardiomyopathy • Mitochondrial disease	Likely pathogenic (Jun 30, 2022)
M-8529-G-A		Cardiomyopathy, apical hypertrophic, and neuropathy	Pathogenic (Mar 01, 2008)
M-8530-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8531-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8533-G-A		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8537-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-8538-T-C			Uncertain significance (Sep 25, 2015)
M-8540-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8541-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-8542-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-8545-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-8547-T-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8548-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-8550-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-8551-T-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8552-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-8553-C-T		Leigh syndrome	Conflicting classifications of pathogenicity (Oct 17, 2019)
M-8554-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8557-G-A		Leigh syndrome • Mitochondrial disease	Benign (Mar 24, 2022)
M-8557-G-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-8560-C-CCCA		Abnormal mitral valve physiology	Pathogenic (-)
M-8562-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-8563-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-8565-A-G			Uncertain significance (Oct 09, 2015)
M-8566-A-G		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. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.
• Disease: DISEASE: Neuropathy, ataxia, and retinitis pigmentosa (NARP) [MIM:551500]: A syndrome characterized by variable combination of developmental delay, psychomotor retardation, hearing loss, optic atrophy and retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy. {ECO:0000269|PubMed:2137962}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. {ECO:0000269|PubMed:7726182}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:17352390, ECO:0000269|PubMed:8395787, ECO:0000269|PubMed:9270604, ECO:0000269|PubMed:9501263, ECO:0000269|PubMed:9556461}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mitochondrial infantile bilateral striatal necrosis (MIBSN) [MIM:500003]: Bilateral striatal necrosis is a neurological disorder resembling Leigh syndrome. {ECO:0000269|PubMed:7668837}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mitochondrial complex V deficiency, mitochondrial 1 (MC5DM1) [MIM:516060]: 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:16049925, ECO:0000269|PubMed:18055910}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, lactic acidosis, and sideroblastic anemia 3 (MLASA3) [MIM:500011]: A rare mitochondrial disorder characterized by sideroblastic anemia, muscle weakness, and exercise intolerance associated with persistent lactic acidemia. Additional MLASA3 features are failure to thrive, hearing loss, epilepsy, stroke- like episodes, and severe developmental delay. {ECO:0000269|PubMed:25037980}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ataxia and polyneuropathy, adult-onset (APAO) [MIM:500010]: A mitochondrial disease characterized by ataxia, axonal sensorimotor polyneuropathy, abnormal eye movements, and dysarthria. {ECO:0000269|PubMed:16049925, ECO:0000269|PubMed:18055910}. 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 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);Mitochondrial Electron Transport Chain;Electron Transport Chain;Oxidative phosphorylation;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: 0.708
• ghis: 0.403

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Mouse Genome Informatics

• Gene name: mt-Atp6

Gene ontology

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