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…

DNmechanismARLOEUF 0.781 OMIM phenotype

Clinical Summary— ATP5PO

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 31 VUS of 54 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ATP5PO

Authoritative clinical overview · Recommended first read

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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

This gene — mechanism propensity

0.73top 25%

GOF

0.4777th %ile

LOF

0.2386th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS31

Likely Benign4

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	1	0	2
Likely Pathogenic	0	0	1	0	1
VUS	0	31	0	0	31
Likely Benign	0	2	0	2	4
Benign	0	0	0	1	1
Total	1	33	2	3	39

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

60 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap ATP5PO — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →