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GeneE
6 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ATP5PF
ATP synthase peripheral stalk subunit F6
Chromosome 21 · 21q21.3
NCBI Gene: 522Ensembl: ENSG00000154723.14HGNC: HGNC:847UniProt: P18859
94PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
proton-transporting ATP synthase activity, rotational mechanismprotein bindingsubstantia nigra developmentproton motive force-driven mitochondrial ATP synthesiscataracttrauma complicationopen-angle glaucomasmoking initiation
✦AI Summary

ATP5PF (ATP synthase peripheral stalk subunit F6) is a structural component of mitochondrial ATP synthase complex (Complex V), which catalyzes ATP synthesis from ADP using the proton gradient generated by the electron transport chain 1. As part of the peripheral stalk, ATP5PF acts as a stator, maintaining the static position of the catalytic α3β3 subcomplex relative to rotating central stalk elements during the rotary mechanism of ATP synthesis 1. ATP5PF is highly expressed in keratinocytes and plays a role in oxidative phosphorylation (OXPHOS) pathway activation. In pemphigus vulgaris, an autoimmune bullous disease, ATP5PF expression is elevated along with other OXPHOS components, and OXPHOS inhibition with metformin attenuates disease-induced cell detachment 2. In non-small cell lung cancer, ATP5PF transcription is activated by the transcription factor POU3F3 downstream of RAS-ERK1 signaling, promoting ATP production and enhancing tumor proliferation and migration 3. During labor, SERPINE1 interacts with ATP5PF to maintain ATP production under hypoxic conditions, supporting myometrial contractility 4. ATP5PF is also dysregulated in Down syndrome amniocytes and associated with mitochondrial dysfunction in ankylosing spondylitis, where its overexpression correlates with shared neurodegenerative disease pathways 5, 6. Additionally, ATP5PF functions as a serum biomarker for monitoring disease progression in Duchenne muscular dystrophy 7.

Sources cited
1
ATP5PF is a structural component of mitochondrial ATP synthase complex peripheral stalk that maintains static positioning of catalytic elements during rotary ATP synthesis mechanism
PMID: 37244256
2
ATP5PF is highly expressed in keratinocytes and involved in OXPHOS pathway activation in pemphigus vulgaris pathogenesis, with OXPHOS inhibition reducing disease severity
PMID: 39373252
3
ATP5PF transcription is activated by POU3F3 transcription factor in RAS-mutant NSCLC cells, promoting ATP production and enhancing cancer cell proliferation and migration
PMID: 39932442
4
ATP5PF interacts with SERPINE1 to enhance ATP production during hypoxic myometrial contraction in labor
PMID: 38100644
5
ATP5PF is a dysregulated chromosome 21 gene associated with mitochondrial dysfunction in Down syndrome developmental disorders
PMID: 38095646
6
ATP5PF is significantly overexpressed in ankylosing spondylitis and involved in shared oxidative phosphorylation pathway with neurodegenerative diseases
PMID: 34664815
7
ATP5PF functions as a serum protein biomarker for monitoring disease progression and treatment response in Duchenne muscular dystrophy clinical trials
PMID: 41503480
Disease Associationsⓘ20
cataractOpen Targets
0.29Weak
trauma complicationOpen Targets
0.28Weak
open-angle glaucomaOpen Targets
0.26Weak
smoking initiationOpen Targets
0.22Weak
Alzheimer diseaseOpen Targets
0.16Weak
osteoarthritis, kneeOpen Targets
0.16Weak
adverse effectOpen Targets
0.16Weak
dementiaOpen Targets
0.14Weak
acute tonsillitisOpen Targets
0.11Weak
response to stimulusOpen Targets
0.11Weak
diabetic ketoacidosisOpen Targets
0.11Weak
pulmonary arterial hypertensionOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
malignant renal pelvis neoplasmOpen Targets
0.05Suggestive
lymphatic system diseaseOpen Targets
0.05Suggestive
vein disorderOpen Targets
0.05Suggestive
neurodegenerative diseaseOpen Targets
0.04Suggestive
late-onset Alzheimers diseaseOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ATP5PBProtein interaction100%ATP5F1DProtein interaction100%NDUFB5Protein interaction100%NDUFA13Protein interaction100%NDUFB3Protein interaction100%NDUFV2Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
45%
Liver
44%
Lung
15%
Bone Marrow
14%
Ovary
14%
Gene Interaction Network
Click a node to explore
ATP5PFATP5PBATP5F1DNDUFB5NDUFA13NDUFB3NDUFV2
PROTEIN STRUCTURE
Preparing viewer…
PDB8H9S · 2.53 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.60 [0.34–1.12]
RankingsWhere ATP5PF stands among ~20K protein-coding genes
  • #5,070of 20,598
    Most Researched94 · top quartile
  • #11,502of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedATP5PF
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Proteomic Analysis Reveals Oxidative Phosphorylation and JAK-STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris.
PMID: 39373252
Exp Dermatol · 2024
1.00
2
Phosphorylation of POU3F3 Mediated Nuclear Translocation Promotes Proliferation in Non-Small Cell Lung Cancer through Accelerating ATP5PF Transcription and ATP Production.
PMID: 39932442
Adv Sci (Weinh) · 2025
0.83
3
Serpin family E member 1 enhances myometrium contractility by increasing ATP production during labor.
PMID: 38100644
FASEB J · 2024
0.67
4
Transcriptome research of human amniocytes identifies hub genes associated with developmental dysplasia in down syndrome.
PMID: 38095646
Aging (Albany NY) · 2023
0.50
5
Evaluation of a serum protein signature as monitoring biomarker for Duchenne Muscular Dystrophy in a long-term clinical trial with corticosteroids.
PMID: 41503480
medRxiv · 2026
0.33