MT-ATP8

Chr MT

ATP synthase F0 subunit 8

Also known as: ATPase8, MTATP8

ATP synthase F0 subunit 8 is a component of Complex V in the mitochondrial respiratory chain, essential for ATP synthesis through oxidative phosphorylation. Mutations cause cardiomyopathy and neuropathy, often occurring as part of single large mitochondrial deletions that also affect MT-ATP6. Inheritance is maternal through mitochondrial DNA, and clinical severity depends on the degree of heteroplasmy.

GeneReviewsOMIMResearchSummary from Curated mito context
Multiplemechanism
Clinical SummaryMT-ATP8
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Gene-Disease Validity (ClinGen)
mitochondrial disease · MTLimited

Limited evidence — not for standalone diagnostic reporting

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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 34 VUS of 114 total submissions
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GeneReview available — MT-ATP8
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

Constraint data not available from gnomAD.

DN
0.94top 5%
GOF
0.6639th %ile
LOF
0.08100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

114 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic5
VUS34
Likely Benign24
Benign37
13
Pathogenic
5
Likely Pathogenic
34
VUS
24
Likely Benign
37
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
Likely Pathogenic
5
VUS
34
Likely Benign
24
Benign
37
Total113

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MT-ATP8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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