ATP5PO

Chr 21AR

ATP synthase peripheral stalk subunit OSCP

Also known as: ATP5O, ATPO, HMC08D05, MC5DN7, OSCP

NCBI Gene: 539 ENSG00000241837 UniProt: P48047 OMIM: 600828

The protein is a subunit of mitochondrial ATP synthase (Complex V) that helps link the catalytic and membrane domains and maintains structural stability during ATP production from ADP. Mutations cause mitochondrial complex V deficiency with autosomal recessive inheritance, resulting in a mitochondrial disorder that affects cellular energy production. This gene has a GeneReviews entry available for detailed clinical guidance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a component of the F-type ATPase found in the mitochondrial matrix. F-type ATPases are composed of a catalytic core and a membrane proton channel. The encoded protein appears to be part of the connector linking these two components and may be involved in transmission of conformational changes or proton conductance. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7MIM #620359

Clinical highlights

Gene–disease validity (ClinGen)

Strong · mitochondrial disease · AR · ClinGen 2024

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Mechanism· predicted

📖

GeneReview available — ATP5PO

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.058

Z-score 2.10

OE 0.34 (0.17–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.03Z-score

OE missense 0.99 (0.85–1.16)

117 obs / 117.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.17–0.78)

0≤0.351.4

Missense OE?0.99 (0.85–1.16)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 4 / 11.8Missense obs/exp: 117 / 117.8Syn Z: -0.48

Background carrier burden — how many people carry a rare variant somewhere in ATP5PO?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

266 rare PASS variants

Rare truncating (LoF)

1 in 4,600

41 rare PASS variants

Rare synonymous (reference)

1 in 550

103 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP5PO. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 300	1 in 4,900
South Asian	~43k	1 in 250	1 in 5,400
Remaining (unassigned)	~30k	1 in 130	1 in 3,800
European (Finnish)	~27k	1 in 610	≈ 1 in 13,000
Admixed American	~22k	1 in 150	≈ 1 in 5,600
African / African American	~21k	1 in 190	1 in 2,100
East Asian	~20k	1 in 240	1 in 2,300
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 180	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓