CMT-ATP6

Genetic Context

HGNC-Approved Gene Symbol

MT-ATP6

Gene Full Name

mitochondrially encoded ATP synthase membrane subunit 6

Chromosome

MT

Zygosity of Responsible Variant

Homoplasmic

Mitochondrial Involvement

Yes

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Hypomorphic

Confidence:
Medium

Prediction:
The literature attributes CMT-ATP6 to loss of function: maternally transmitted MT-ATP6 missense variants such as m.9185T>C impair proton translocation through subunit a of the ATP synthase Fo domain, lowering ATP output in peripheral nerve. Pathogenic alleles in this presentation are typically homoplasmic or carried at high heteroplasmy, and severity tracks the proportion of mutant mitochondrial genomes, the threshold behaviour familiar from the m.8993T>G NARP allele at the same gene.

Rationale:
Substituted residues in subunit a line the proton half-channel that couples rotation to ATP synthesis, so the deficit is energetic rather than toxic. Because mutant subunit a is still built into an assembled ATP synthase, how much of the impairment reflects lost proton conduction and how much reflects poor coupling within the complex is not settled, and the confidence grade reflects that unresolved point.

ClinVar Pathogenic Variants

View MT-ATP6 ClinVar Variants

MT-ATP6 OMIM Entry

MT-ATP6 OMIM