ATP5F1A

Chr 18ARAD

ATP synthase F1 subunit alpha

Also known as: ATP5A, ATP5A1, ATP5AL2, ATPM, COXPD22, HEL-S-123m, MC5DN4, MC5DN4A

NCBI Gene: 498 ENSG00000152234 UniProt: P25705 OMIM: 164360

This gene encodes the alpha subunit of the F1 catalytic core of mitochondrial ATP synthase, which synthesizes ATP using the proton electrochemical gradient across the inner mitochondrial membrane during oxidative phosphorylation. Mutations cause mitochondrial complex V (ATP synthase) deficiency with nuclear types 4A and 4B, presenting as combined oxidative phosphorylation deficiency and encephalopathy. The condition follows both autosomal recessive and autosomal dominant inheritance patterns.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the different isoforms have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16. [provided by RefSeq, Mar 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 22MIM #616045

?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B, encephalopathic typeMIM #615228

Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4AMIM #620358

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

Multiple*

Mechanism· predicted