MT-ATP6

Chr MT

ATP synthase F0 subunit 6

Also known as: ATPase6, MTATP6

NCBI Gene: 4508 ENSG00000198899 UniProt: P00846 OMIM: 516060

This gene encodes ATP synthase F0 subunit 6, a component of Complex V that synthesizes ATP in the mitochondrial respiratory chain. Mutations cause NARP syndrome at 70-90% heteroplasmy levels, maternally inherited Leigh syndrome at >90% heteroplasmy, and Charcot-Marie-Tooth-like neuropathy, with phenotype severity strongly dependent on the degree of heteroplasmy. Inheritance is maternal through the mitochondrial genome.

GeneReviews OMIM ResearchSummary from Curated mito context

Enables proton channel activity. Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in proton motive force-driven mitochondrial ATP synthesis and proton transmembrane transport. Located in mitochondrion. Part of proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeuropathy, ataxia, and retinitis pigmentosa

UniProtLeber hereditary optic neuropathy

UniProtLeigh syndrome

UniProtMitochondrial infantile bilateral striatal necrosis

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — MT-ATP6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Nuclear-gene analyses omitted

MT-ATP6 is a mitochondrial protein-coding gene. gnomAD constraint, carrier burden and exome coverage, the ClinVar type breakdown, AlphaFold and transcript-architecture views are built for nuclear genes and are not shown. Population data for mtDNA variants (gnomAD v3.1, homoplasmy and heteroplasmy) is on each variant page.

Where it sits in the mitochondrial genome

Tap or hover a gene, landmark or tick; genes open their page, ticks their variant.

proteinrRNAtRNAouter ring H-strand · inner L-strandMITOMAP confirmedreported (as of 2026-10-07)

37 genes from Ensembl (rCRS numbering, matched to MITOMAP’s Gene Loci); landmarks and disease alleles from MITOMAP (CC BY 3.0). Circular layout after MitoWheel.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MT-ATP6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

MITOMAP Disease Variants — MT-ATP6

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.8527A>G	ATP8:K54K ATP6:M1M	Neuromuscular disorder, possible helper mutation / dlated cardiomyopathy	Reported	324
m.8528T>C	ATP8:W55R ATP6:M1T	Infantile cardiomyopathy / hyperammonemia / ATP6/8 deficiency	Likely pathogenic · confirmed	0
m.8529G>A	ATP8:W55Term ATP6:M1M	Apical HCM	Uncertain significance · reported	0
m.8535A>G	ATP8:K57Term ATP6:E3E	ATP6/8 deficiency	Reported	0
m.8551T>C	ATP8:H62H ATP6:F9L	Possible LHON helper mutation	Reported	18
m.8558C>T	ATP8:P65S ATP6:A11V	Possibly LVNC cardiomyopathy-associated	Reported	15
m.8561C>G	ATP8:P66A ATP6:P12R	Ataxia w neuropathy, DM, SNHL, and hypogonadism	Reported	0
m.8561C>T	ATP8:P66S ATP6:P12L	Ataxia w psychomotor delay	Reported	0
m.8570T>C	ATP8:Term69Q ATP6:L15P	Congenital sideroblastic anemia (CSA) / ATP6/8 deficiency / MILS	Uncertain significance · reported	0
m.8572G>A	ATP8:Term69Term ATP6:G16S	Spinocerebellar ataxia	Reported	275
m.8573G>A	G16D	Patient with suspected mitochondrial disease	Reported	68
m.8578C>T	P18S	Spinocerebellar ataxia	Reported	31
m.8579C>T	P18L	ATP6/8 deficiency	Reported	0
m.8597T>C	I24T	Leigh Syndrome	Reported	19
m.8605C>T	P27S	Isolated mitochondrial cardiomyopathy	Reported	5
m.8606C>T	P27L	Possible association with sepsis	Reported	0
m.8608C>T	P28S	Patient with suspected mitochondrial disease	Reported	3
m.8611C>A	L29M	Neurodevelopmental delay +cerebellar atrophy +strabismus	Reported	5
m.8611C>CC	frameshift	Ataxia, microcephaly, developmental delay, intellectual disability / ATP6/8 deficiency	Reported	0
m.8612T>C	L29P	Arm and leg weakness, incontinence, developmental delay, autism, epilepsy / ATP6/8 deficiency	Reported	0
m.8618T>TT	frameshift	NARP/cognitive decline+abnormal brain MRI+impaired kidney function	Likely pathogenic · confirmed	0
m.8639T>C	I38T	Possible LHON modulator	Reported	26
m.8668T>C	W48R	LHON	Reported	48
m.8672T>C	L49P	lntrauterine growth retardation+truncal hypotonia+microcephaly+developmental delay+left ventricular noncompaction+WPW	Reported	0
m.8691A>G	K55K	Infantile mito disease w subclinical hypothyroidism	Reported	7
m.8716A>TA	frameshift	ATP6/8 deficiency	Reported	0
m.8719G>A	G65Term	Suspected mito disease	Uncertain significance · reported	0
m.8723G>T	R66L	Patient with suspected mitochondrial disease / ATP6/8 deficiency	Reported	0
m.8741T>G	L72R	MILS protective factor	Reported	0
m.8746T>C	S74P	ATP6/8 deficiency	Reported	0
m.8777T>C	L84P	Adult-onset cerebellar ataxia�	Reported	0
m.8779C>T	L85F	Possible LHON modulator	Reported	1
m.8782G>A	G86Term	Cerebellar ataxia+diabetes+kidney disease / ataxia+myoclonic epilepsy / ATP6/8 deficiency	Reported	0
m.8783G>A	G86E	Unspecified suspected mitochondrial disorder	Uncertain significance · reported	2
m.8794C>T	H90Y	Exercise Endurance / Coronary Atherosclerosis risk	Reported	1,831
m.8795A>G	H90R	MILS protective factor	Reported	0
m.8797T>C	S91P	Leigh syndrome spectrum	Reported	0
m.8806C>G	P94A	Suspected mito disease	Reported	0
m.8812A>G	T96A	Spinocerebellar ataxia / PCOS patient	Reported	78
m.8821T>G	S99A	Possible LHON helper variant	Reported	0
m.8836A>G	M104V	LHON	Reported	187
m.8839G>C	A105P	NARP syndrome	Uncertain significance · reported	0
m.8843T>C	I106T	Patient with suspected mitochondrial disease / PCOS patient	Reported	235
m.8851T>C	W109R	BSN / Leigh syndrome	Uncertain significance · confirmed	4
m.8858G>A	G111D	ATP6/8 deficiency	Reported	0
m.8879G>T	R118L	Adult-onset cerebellar ataxia�- possible helper mutant for m.8777C	Reported	0
m.8881T>C	S119P	Patient with suspected mitochondrial disease	Reported	3
m.8890A>G	K122E	Juvenile-onset metabolic syndrome	Reported	0
m.8902G>A	A126T	Suspected mito disease	Reported	10
m.8909T>C	F128S	Recurrent severe kidney disease and multiple systemic dysfunctions	Reported	0
m.8921G>A	G132D	Patient with suspected mitochondrial disease	Reported	9
m.8932C>T	P136S	Prostate tumor / Neuromuscular disorder / dilated cardiomyopathy	Benign · reported	325
m.8936T>A	L137H	Atypical Leigh syndrome	Uncertain significance · reported	1
m.8938A>G	I138V	Patient with suspected mitochondrial disease	Reported	52
m.8950G>A	V142I	LDYT / Spinocerebellar Ataxia	Reported	86
m.8951T>C	V142A	Patient with ataxia	Reported	11
m.8959G>A	E145K	Developmental delay, intellectual disability, low citrilline / ATP6/8 deficiency	Reported	4
m.8969G>C	S148T	Suspected mito disease	Reported	0
m.8969G>A	S148N	Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) / IgG nephropathy / ATP6/8 deficiency	Likely pathogenic · confirmed	1
m.8975T>C	L150P	Suspected mito disease	Reported	24
m.8989G>C	A155P	NARP syndrome	Reported	0
m.8993T>C	L156P	NARP / Leigh Disease / MILS / ATP6/8 deficiency / other	Pathogenic · confirmed	2
m.8993TG>CA	L156P	Developmental delay & myopathy	Likely pathogenic · confirmed	0
m.8993T>G	L156R	NARP / Leigh Disease / MILS / ATP6/8 deficiency / other	Pathogenic · confirmed	6
m.8999T>C	V158A	Patient with suspected mitochondrial disease	Reported	9
m.9005T>C	L160P	ATP6/8 deficiency	Reported	2
m.9008C>G	T161S	Suspected mito disease	Reported	2
m.9010G>A	A162T	Unspecified neurological disorder	Reported	30
m.9016A>G	I164V	LHON	Reported	13
m.9017T>C	I164T	Unspecified neurological disorder	Reported	14
m.9019A>G	T165A	Suspected mito disease	Reported	0
m.9025G>A	G167S	Motor neuropathy, Leigh-like, colon cancer	Uncertain significance · reported	46
m.9026G>A	G167D	Spinocerebellar ataxia / patient with suspected mitochondrial disease	Uncertain significance · reported	3
m.9029A>G	H168R	LHON-like	Reported	2
m.9032T>C	L169P	NARP / Complex phenotype with microcephaly, ataxia, hearing loss, lactic acidosis / ATP6/8 deficiency	Uncertain significance · reported	0
m.9035T>C	L170P	Ataxia syndromes / ATP6/8 deficiency	Likely pathogenic · confirmed	0
m.9041A>G	H172R	Patient with suspected mitochondrial disease	Reported	52
m.9049G>A	G175Term	Unspecified suspected mitochondrial disorder / ATP6/8 deficiency	Uncertain significance · reported	0
m.9055G>A	A177T	PD protective factor	Reported	2,649
m.9058A>G	T178A	Patients with (1) LVNC cardiomyopathy; (2) autism, intellectual disability, epilepsy; (3) PCOS	Reported	41
m.9071C>T	S182L	Potentially functional variant cosegregating with LHON3635A	Reported	16
m.9088T>C	S188P	Patient with suspected mitochondrial disease	Reported	25
m.9098T>C	I191T	Predisposition to anti-retroviral mito disease	Reported	69
m.9101T>C	I192T	LHON	Reported	67
m.9115A>G	I197V	Patient with suspected mitochondrial disease	Reported	34
m.9127AT>-	IL-PTerm	NARP	Reported	0
m.9133G>A	E203K	Patient with suspected mitochondrial disease	Reported	4
m.9134A>G	E203G	Hypotonia, lactic acidosis, HCM, IUGR	Uncertain significance · reported	0
m.9139G>A	A205T	LHON	Reported	52
m.9152T>C	I209T	Patient with suspected mitochondrial disease	Uncertain significance · reported	17
m.9154C>T	Q210Term	Peripheral neuropathy ataxia IgA nephropathy	Reported	0
m.9155A>G	Q210R	MIDD, renal insufficiency	Likely pathogenic · confirmed	0
m.9155A>T	Q210L	Developmental delay, intellectual disability, low citrilline	Reported	0
m.9157G>A	A211T	Mitochondrial neuromuscular disease	Reported	6
m.9166T>C	F214L	EXIT+more / bilateral optic neuropathy	Reported	0
m.9176T>G	L217R	Leigh Disease / Spastic Paraplegia / Spinocerebellar Ataxia / ATP6/8 deficiency	Likely pathogenic · confirmed	1
m.9176T>C	L217P	FBSN / Leigh Disease / Spinocerebellar Ataxia / ATP6/8 deficiency	Pathogenic · confirmed	3
m.9185T>C	L220P	Leigh Disease / Ataxia syndromes / NARP-like disease / Episodic weakness and Charcot-Marie-Tooth / ATP6/8 deficiency	Pathogenic · confirmed	3
m.9191T>C	L222P	Leigh Disease	Likely pathogenic · confirmed	0
m.9204AT>-	frameshift	ATP6/8 deficiency	Reported	0
m.9205TA>-	Term-M	Encephalopathy / Seizures / Lacticacidemia	Likely pathogenic · confirmed	0