ATPAF2

Chr 17AR

ATP synthase mitochondrial F1 complex assembly factor 2

Also known as: ATP12, ATP12p, LP3663, MC5DN1

NCBI Gene: 91647ENSG00000171953UniProt: Q8N5M1

This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1MIM #604273
AR
376
ClinVar variants
117
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ATPAF2
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
117 Pathogenic / Likely Pathogenic· 155 VUS of 376 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.44LOEUF
pLI 0.000
Z-score 0.29
OE 0.92 (0.61–1.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.85 (0.74–0.98)
142 obs / 167.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.92 (0.61–1.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.74–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 14 / 15.2Missense obs/exp: 142 / 167.1Syn Z: 0.60

ClinVar Variant Classifications

376 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
Likely Pathogenic1
VUS155
Likely Benign73
Benign18
Conflicting13
116
Pathogenic
1
Likely Pathogenic
155
VUS
73
Likely Benign
18
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
116
0
116
Likely Pathogenic
1
0
0
0
1
VUS
5
116
31
3
155
Likely Benign
0
6
37
30
73
Benign
0
1
16
1
18
Conflicting
—13
Total612320034376

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

View in ClinVar →

Protein Context — Lollipop Plot

ATPAF2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1

MIM #604273

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nuclear genetic defects of mitochondrial ATP synthase.
Hejzlarová K et al.·Physiol Res
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools