ATP5F1A

Summary

ATP5F1A (ATP synthase F1 subunit alpha, HGNC:823) is a protein-coding gene on chromosome 18q21.1, encoding ATP synthase F(1) complex subunit alpha, mitochondrial (P25705). Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. It is a selective cancer dependency (DepMap: 57.9% of cell lines).

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.

Source: NCBI Gene 498 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 314 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 57.9% of screened cell lines
• MANE Select transcript: NM_004046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:823
Approved symbol	ATP5F1A
Name	ATP synthase F1 subunit alpha
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ATP5A, hATP1, OMR, ORM
Ensembl gene	ENSG00000152234
Ensembl biotype	protein_coding
OMIM	164360
Entrez	498

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 20 protein_coding, 5 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000282050, ENST00000398752, ENST00000585650, ENST00000586523, ENST00000586592, ENST00000587902, ENST00000588390, ENST00000589252, ENST00000589611, ENST00000589869, ENST00000590156, ENST00000590324, ENST00000590406, ENST00000590448, ENST00000590665, ENST00000591267, ENST00000591981, ENST00000592364, ENST00000592989, ENST00000593152, ENST00000858812, ENST00000858813, ENST00000858814, ENST00000858815, ENST00000858816, ENST00000858817, ENST00000858818, ENST00000939704, ENST00000939705, ENST00000939706, ENST00000966007

RefSeq mRNA: 5 — MANE Select: NM_004046 NM_001001935, NM_001001937, NM_001257334, NM_001257335, NM_004046

CCDS: CCDS11927, CCDS58620, CCDS59315

Canonical transcript exons

ENST00000398752 — 12 exons

Exon	Start	End
ENSE00003536889	46089566	46089732
ENSE00003559364	46091682	46091851
ENSE00003571939	46089823	46089996
ENSE00003631824	46098172	46098296
ENSE00003638639	46087341	46087492
ENSE00003640222	46095053	46095131
ENSE00003661484	46088109	46088257
ENSE00003663774	46087008	46087232
ENSE00003666949	46084504	46084654
ENSE00003678882	46086387	46086494
ENSE00003684250	46086113	46086257
ENSE00003748171	46080248	46084363

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 199.6084 / max 11650.0527, expressed in 1827 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171796	195.9802	1827
171794	1.9657	940
208550	0.8383	464
171800	0.4012	146
171803	0.2394	95
171799	0.0918	20
171802	0.0737	18
171801	0.0181	1

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.91	gold quality
esophagus squamous epithelium	UBERON:0006920	99.88	gold quality
renal medulla	UBERON:0000362	99.87	gold quality
middle temporal gyrus	UBERON:0002771	99.85	gold quality
jejunal mucosa	UBERON:0000399	99.84	gold quality
tibia	UBERON:0000979	99.83	gold quality
parietal pleura	UBERON:0002400	99.83	gold quality
left ventricle myocardium	UBERON:0006566	99.82	gold quality
adult organism	UBERON:0007023	99.82	gold quality
nephron tubule	UBERON:0001231	99.81	gold quality
epithelium of nasopharynx	UBERON:0001951	99.81	gold quality
epithelium of esophagus	UBERON:0001976	99.80	gold quality
pigmented layer of retina	UBERON:0001782	99.79	gold quality
palpebral conjunctiva	UBERON:0001812	99.79	gold quality
jejunum	UBERON:0002115	99.79	gold quality
myocardium	UBERON:0002349	99.79	gold quality
germinal epithelium of ovary	UBERON:0001304	99.78	gold quality
biceps brachii	UBERON:0001507	99.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.78	gold quality
pleura	UBERON:0000977	99.77	gold quality
pons	UBERON:0000988	99.77	gold quality
body of tongue	UBERON:0011876	99.77	gold quality
secondary oocyte	CL:0000655	99.76	gold quality
colonic mucosa	UBERON:0000317	99.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.76	gold quality
cardiac ventricle	UBERON:0002082	99.75	gold quality
heart left ventricle	UBERON:0002084	99.75	gold quality
visceral pleura	UBERON:0002401	99.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.74	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	21.66
E-MTAB-10042	yes	13.40
E-HCAD-25	yes	8.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H4, USF2, YY1

miRNA regulators (miRDB)

18 targeting ATP5F1A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-4774-5P	95.92	68.27	827

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 57.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 37)

• The alpha-chain of ATP synthase is implicated in neurofibrillary degeneration of Alzheimer’s disease that is illustrated by the cytosolic accumulation of this mitochondrial protein, which belongs to the mitochondrial respiratory system. (PMID:12614671)
• Within the structurally-confined internal aqueous cavity of the F1-motor of ATP synthase, function results from free energy changes that shift the balance between interfacial charge hydration and interfacial hydrophobic hydration. (PMID:16378738)
• analysis of vascular endothelial ectoadenylate kinase and plasma membrane ATP synthase (PMID:16714292)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Higher levels of ATP5a1 expression are associated with certain Single Nucleotide Polymorphisms and with TP53 mutation. (PMID:19261598)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• These data show that an linoleic acid-phospholipid induced stimulation in hepatic HDL secretion is related to the expression and function of membrane ATP metabolizing proteins. (PMID:19717637)
• This protein has been found differentially expressed in the anterior cingulate cortex in men patients with schizophrenia. (PMID:20381070)
• Data suggest that F1-ATPase catalytic site show the correlation between the phosphate binding and the tightening of the alphabeta-interface. (PMID:21481781)
• A selective Cys in ATP synthase alpha subunit is targeted by multiple oxidative posttranslational modifications suggesting that this Cys residue may act as a redox sensor modulating ATP synthase function. (PMID:21817160)
• Antibodies to the beta- and gamma-subunits of F(1)-ATPase are further antimitochondrial antibodies in primary biliary cirrhosis. (PMID:22098431)
• An interactive proteomics study was done to examine proteins that bind heterocomplexes with ABCC1 using coimmunoprecipitation and MS/MS analyses. We found that ATP synthase alpha binds to ABCC1 in plasma membranes with a ratio of 2:1. (PMID:22188235)
• F1-ATPase at the cell surface of colonic epithelial cells has a role in mediating cell proliferation (PMID:23055519)
• Studies indicate that F1-ATPase (F1) is a rotary motor protein driven by ATP hydrolysis and the minimum complex of F1 for function as a rotary motor is the alpha3beta3gamma subcomplex. (PMID:23395605)
• Homozygous mutations in this gene are the likely cause of mitochondrial disease in two sisters, with support from a yeast model. (PMID:23596069)
• A mutation in ATP5A1 causes a fatal neonatal mitochondrial encephalopathy. (PMID:23599390)
• Studies indicate that the F-ATP synthase can reversibly undergo a Ca(2+)-dependent transition to form a channel that mediates the permeability transition. (PMID:25999424)
• Mitochondrial calpain-1 disrupts ATP synthase, leading to mitochondrial reactive oxygen species generation, which promotes proinflammatory response and myocardial dysfunction during endotoxemia. (PMID:26246018)
• Here, we found that ATP synthase subunit alpha (ATP5A) was O-GlcNAcylated at Thr432 and ATP5A O-GlcNAcylation was decreased in the brains of AD patients and transgenic mouse model (PMID:26358770)
• High mRNA levels of ATP5A1 are associated with glioblastoma. (PMID:26526033)
• Hemoglobin - a novel ligand of hepatocyte ectopic F1-ATPase (PMID:26769832)
• These findings, together with the previously reported inhibition of respiratory complex I, show that depression of the activity of oxidative phosphorylation enzymes is involved in the cell growth inhibitory action of ATRA. (PMID:27856255)
• these data highlight a key role of the P2Y1/PI3Kbeta axis in endothelial cell proliferation downstream of ecto-F1-ATPase activation by apoA-I. Pharmacological targeting of this pathway could represent a promising approach to enhance vascular endothelial protection. (PMID:28578353)
• The study demonstrates a novel role of FANCD2 in governing cellular ATP production via ATP5A, and advances the understanding of how defective Fanconi anemia signaling contributes to aging and cancer at the energy metabolism level. (PMID:28687786)
• This cohort study showed that the ATP5A1 gene was down regulation between patients with idiopathic Parkinson disease and controls (PMID:28916538)
• Using systems biology techniques to study gene coexpression network, ATP5A1 was identified and found highly expressed in normal kidney than clear cell renal cell carcinoma (ccRCC) tissues of each grade. Functional and pathway enrichment analysis demonstrated that ATP5A1 is overrepresented in pathway of oxidative phosphorylation, which associated with tumorigenesis and tumor progression. (PMID:29207195)
• 17% of prostate carcinomas and 18% of benign prostate tissues showed isolated or combined deficiency of oxidative phosphorylation complexes. ATP5F1A, a complex V protein, was the most frequently affected subunit (PMID:30538797)
• Poly(GR) bound preferentially to the mitochondrial complex V component ATP5A1 and enhanced its ubiquitination and degradation, consistent with reduced ATP5A1 protein level in both (GR)80 mouse neurons and amyotrophic lateral sclerosis and frontotemporal dementia patient brains (PMID:31086314)
• F0F1 ATP synthase regulates extracellular calcium influx in human neutrophils by interacting with Cav2.3 and modulates neutrophil accumulation in the lipopolysaccharide-challenged lung. (PMID:32019549)
• Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase. (PMID:34376679)
• A recurrent de novo ATP5F1A substitution associated with neonatal complex V deficiency. (PMID:34483339)
• ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells. (PMID:34520292)
• Growth arrest and DNA damage-inducible alpha regulates muscle repair and fat infiltration through ATP synthase F1 subunit alpha. (PMID:36511343)
• Meta-analysis of brain samples of individuals with schizophrenia detects down-regulation of multiple ATP synthase encoding genes in both females and males. (PMID:36640659)
• Proteomic analyses identify HK1 and ATP5A to be overexpressed in distant metastases of lung adenocarcinomas compared to matched primary tumors. (PMID:38016997)
• Overexpression of ATP5F1A in Cardiomyocytes Promotes Cardiac Reverse Remodeling. (PMID:38910562)
• BRG1 promotes liver cancer cell proliferation and metastasis by enhancing mitochondrial function and ATP5A1 synthesis through TOMM40. (PMID:38978225)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp5fa1	ENSDARG00000010149
mus_musculus	Atp5f1a	ENSMUSG00000025428
rattus_norvegicus	Atp5f1a	ENSRNOG00000017032
drosophila_melanogaster	blw	FBGN0011211
caenorhabditis_elegans	T26E3.7	WBGENE00012040

Paralogs (4): ATP5F1B (ENSG00000110955), ATP6V1A (ENSG00000114573), ATP6V1B1 (ENSG00000116039), ATP6V1B2 (ENSG00000147416)

Protein

Protein identifiers

ATP synthase F(1) complex subunit alpha, mitochondrial — P25705 (reviewed: P25705)

Alternative names: ATP synthase F1 subunit alpha

All UniProt accessions (12): P25705, A0A0A0MTS3, K7EJP1, K7EK77, K7EKV9, K7EM08, K7ENJ4, K7EQH4, K7EQU6, K7ERX7, K7ESA0, V9HW26

UniProt curated annotations — full annotation on UniProt →

Function. Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel. These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro. With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites. Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions.

Subunit / interactions. Homotrimer. Component of the ATP synthase complex composed at least of ATP5F1A/subunit alpha, ATP5F1B/subunit beta, ATP5MC1/subunit c (homooctamer), MT-ATP6/subunit a, MT-ATP8/subunit 8, ATP5ME/subunit e, ATP5MF/subunit f, ATP5MG/subunit g, ATP5MK/subunit k, ATP5MJ/subunit j, ATP5F1C/subunit gamma, ATP5F1D/subunit delta, ATP5F1E/subunit epsilon, ATP5PF/subunit F6, ATP5PB/subunit b, ATP5PD/subunit d, ATP5PO/subunit OSCP. ATP synthase complex consists of a soluble F(1) head domain (subunits alpha(3) and beta(3)) - the catalytic core - and a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, e, f, g, k and j). These two domains are linked by a central stalk (subunits gamma, delta, and epsilon) rotating inside the F1 region and a stationary peripheral stalk (subunits F6, b, d, and OSCP). Interacts with ATPAF2. Interacts with HRG; the interaction occurs on the surface of T-cells and alters the cell morphology when associated with concanavalin (in vitro). Interacts with PLG (angiostatin peptide); the interaction inhibits most of the angiogenic properties of angiostatin. Interacts with BLOC1S1. Interacts with BCL2L1 isoform BCL-X(L); the interaction mediates the association of BCL2L1 isoform BCL-X(L) with the mitochondrial membrane F(1)F(0) ATP synthase and enhances neurons metabolic efficiency. Interacts with CLN5 and PPT1. Interacts with S100A1; this interaction increases F1-ATPase activity. Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes.

Subcellular location. Mitochondrion. Mitochondrion inner membrane. Cell membrane.

Tissue specificity. Fetal lung, heart, liver, gut and kidney. Expressed at higher levels in the fetal brain, retina and spinal cord.

Post-translational modifications. The N-terminus is blocked. Acetylated on lysine residues. BLOC1S1 is required for acetylation.

Disease relevance. Combined oxidative phosphorylation deficiency 22 (COXPD22) [MIM:616045] A mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure. The disease is caused by variants affecting the gene represented in this entry. Mitochondrial complex V deficiency, nuclear type 4A (MC5DN4A) [MIM:620358] An autosomal dominant mitochondrial disorder characterized by failure to thrive, feeding difficulties, hyperlactatemia, hyperammonemia, and increased serum alanine levels. Some affected individuals show spontaneous resolution of the symptoms in early childhood and have subsequent normal growth and development, whereas others show developmental delay with impaired intellectual development and movement abnormalities, including dystonia, ataxia, or spasticity. The disease is caused by variants affecting the gene represented in this entry. Mitochondrial complex V deficiency, nuclear type 4B (MC5DN4B) [MIM:615228] An autosomal recessive mitochondrial disorder characterized by severe neonatal encephalopathy resulting in death in the first weeks of life. Affected individuals do not show dysmorphic features or organomegaly, and manifest neurologic features such as irritability, a high-pitched cry, a horizontal and vertical nystagmus, abnormal primitive reflexes, and tonus dysregulation. Post-mortem anatomopathological examination shows extensive cerebral damage, hypoplastic lungs, and renal and skeletal lesions. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The siderophore enterobactin (Ent) produced by enteric bacteria binds Fe(3+) and helps bacteria scavenge iron ions from the environment. As a consequence, the mammalian siderocalin LCN2 plays an important role in defense against bacterial infections by sequestering iron bound to microbial siderophores. LCN2 can also bind iron bound to endogenous or nutrient-derived iron chelators and plays an important role in cellular iron homeostasis. Enterobactin produced by non-pathogenic E.coli strains can facilitate mitochondrial iron assimilation, suggesting that iron bound to siderophores from non-pathogenic bacteria may contribute to iron absorption by the host.

Similarity. Belongs to the ATPase alpha/beta chains family.

Isoforms (3)

UniProt ID	Names	Canonical?
P25705-1	1	yes
P25705-2	2
P25705-3	3

RefSeq proteins (5): NP_001001935, NP_001001937, NP_001244263, NP_001244264, NP_004037* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000194	ATPase_F1/V1/A1_a/bsu_nucl-bd	Domain
IPR000793	ATP_synth_asu_C	Domain
IPR004100	ATPase_F1/V1/A1_a/bsu_N	Domain
IPR005294	ATP_synth_F1_asu	Family
IPR020003	ATPase_a/bsu_AS	Active_site
IPR023366	ATP_synth_asu-like_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR033732	ATP_synth_F1_a_nt-bd_dom	Domain
IPR036121	ATPase_F1/V1/A1_a/bsu_N_sf	Homologous_superfamily
IPR038376	ATP_synth_asu_C_sf	Homologous_superfamily

Pfam: PF00006, PF00306, PF02874

UniProt features (109 total): modified residue 36, helix 22, strand 20, binding site 9, sequence variant 6, sequence conflict 6, turn 4, splice variant 2, transit peptide 1, chain 1, site 1, glycosylation site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8H9E	ELECTRON MICROSCOPY	2.53
8H9S	ELECTRON MICROSCOPY	2.53
8H9L	ELECTRON MICROSCOPY	2.61
8H9U	ELECTRON MICROSCOPY	2.61
8H9I	ELECTRON MICROSCOPY	2.77
8H9T	ELECTRON MICROSCOPY	2.77
8KI3	ELECTRON MICROSCOPY	2.89
8H9P	ELECTRON MICROSCOPY	3.02
8H9V	ELECTRON MICROSCOPY	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25705-F1	88.47	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 413 (required for activity)

Ligand- & substrate-binding residues (9): 475; 215; 217; 218; 219; 219; 220; 312; 473

Post-translational modifications (36): 53, 65, 76, 106, 123, 126, 132, 134, 161, 161, 166, 167, 167, 184, 204, 230, 230, 239, 239, 240 …

Glycosylation sites (1): 76

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-163210	Formation of ATP by chemiosmotic coupling
R-HSA-8949613	Cristae formation
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-392499	Metabolism of proteins
R-HSA-9609507	Protein localization

MSigDB gene sets: 489 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, RRAGTTGT_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, MORF_HDAC1, DITTMER_PTHLH_TARGETS_UP, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (13): negative regulation of endothelial cell proliferation (GO:0001937), lipid metabolic process (GO:0006629), ATP biosynthetic process (GO:0006754), response to muscle activity (GO:0014850), proton motive force-driven ATP synthesis (GO:0015986), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), positive regulation of blood vessel endothelial cell migration (GO:0043536), response to ethanol (GO:0045471), cellular response to dexamethasone stimulus (GO:0071549), cellular response to nitric oxide (GO:0071732), monoatomic ion transport (GO:0006811), ATP metabolic process (GO:0046034), proton transmembrane transport (GO:1902600)

GO Molecular Function (11): protease binding (GO:0002020), RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), MHC class I protein binding (GO:0042288), ADP binding (GO:0043531), angiostatin binding (GO:0043532), proton-transporting ATP synthase activity, rotational mechanism (GO:0046933), nucleotide binding (GO:0000166), protein binding (GO:0005515), adenyl ribonucleotide binding (GO:0032559)

GO Cellular Component (13): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), membrane raft (GO:0045121), proton-transporting ATP synthase complex (GO:0045259), extracellular exosome (GO:0070062), sperm end piece (GO:0097229), cytoplasm (GO:0005737), proton-transporting two-sector ATPase complex (GO:0016469), transmembrane transporter complex (GO:1902495)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Protein localization	1
Aerobic respiration and respiratory electron transport	1
Mitochondrial biogenesis	1
Metabolism of proteins	1
Metabolism	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
mitochondrion	2
proton motive force-driven ATP synthesis	2
adenyl ribonucleotide binding	2
membrane protein complex	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
primary metabolic process	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
response to activity	1
ATP biosynthetic process	1
oxidative phosphorylation	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
response to alcohol	1
cellular response to glucocorticoid stimulus	1
response to dexamethasone	1
cellular response to ketone	1
response to nitric oxide	1
cellular response to oxygen-containing compound	1
cellular response to reactive nitrogen species	1
transport	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
monoatomic cation transmembrane transport	1
enzyme binding	1
nucleic acid binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
MHC protein binding	1
anion binding	1
protein binding	1
proton channel activity	1
ligase activity	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

5086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5F1A	ATP5F1C	P36542	994
ATP5F1A	ATP5F1D	P30049	982
ATP5F1A	ATPAF1	Q5TC12	980
ATP5F1A	ATP5F1E	P56381	974
ATP5F1A	ATPAF2	Q8N5M1	971
ATP5F1A	ATP5PO	P48047	954
ATP5F1A	ATP5F1B	P06576	931
ATP5F1A	ATP5PB	P24539	883
ATP5F1A	UQCRC2	P22695	867
ATP5F1A	NDUFB8	O95169	840
ATP5F1A	ATP5MC1	P05496	838
ATP5F1A	ATP5PD	O75947	832
ATP5F1A	SDHA	P31040	826
ATP5F1A	NDUFA9	Q16795	825
ATP5F1A	SDHB	P21912	811

IntAct

274 interactions, top by confidence:

A	B	Type	Score
ATP5PB	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.860
ATP5F1B	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.800
ATP5PB	ATP5PD	psi-mi:“MI:0915”(physical association)	0.760
ATP5PF	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ATP5PB	SLC19A2	psi-mi:“MI:0914”(association)	0.640
ACKR3	ATP5F1B	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
ATP5F1A	ATP5PO	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1A	HTT	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1A	ATPAF2	psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SIRT3	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.520
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (800): ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Co-fractionation), ATP5B (Two-hybrid), ATP5A1 (Affinity Capture-RNA), ATP5A1 (Affinity Capture-RNA), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS)

ESM2 similar proteins: A1A699, A2YQ56, A2Z928, A5A6H5, B8B4H5, B9FK36, B9FSH5, B9HQZ6, C5Z7K4, F4I1L3, O04130, O04979, O65796, O80983, P05165, P08428, P0C587, P0DTA4, P14882, P15999, P19483, P25705, P42762, P42804, P49294, P49295, P93111, Q03265, Q0E3C8, Q2KNB7, Q42777, Q42843, Q5R546, Q5W676, Q69UZ3, Q69XQ6, Q6H795, Q6Z398, Q75GT3, Q7F8T6

Diamond homologs: A0LDA2, A1ALL5, A1B8N8, A1UR47, A1VXI8, A3PIB7, A4WUM9, A4YKD8, A5A6H5, A5E948, A5FZ52, A5G9D6, A5V3X3, A5VSE3, A6UDM3, A6WXW9, A7HT50, A7IH29, A8FJR0, A8HS15, A8LJR6, A9H9A4, A9IYX0, A9M839, A9W2R3, A9WWS4, B0T338, B0UE41, B1LVH1, B1ZEE9, B2S7M5, B3EA03, B3PQ70, B4RD45, B5ZSN9, B6JD06, B7KUA4, B8EQP9, B8FGT6, B8H5I2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5F1A	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 222 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of ATP by chemiosmotic coupling	7	26.1×	4e-06
Cristae formation	7	15.8×	6e-05
Selective autophagy	6	10.9×	2e-03
Mitochondrial biogenesis	9	9.9×	6e-05
Dectin-1 mediated noncanonical NF-kB signaling	6	8.4×	6e-03
Activation of NF-kappaB in B cells	6	7.7×	8e-03
Mitochondrial protein degradation	10	7.5×	1e-04
Aerobic respiration and respiratory electron transport	12	6.9×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	7	29.3×	2e-06
proton motive force-driven mitochondrial ATP synthesis	10	13.7×	2e-06
autophagosome maturation	6	11.0×	6e-03
autophagosome assembly	7	8.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

314 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	131
Likely benign	90
Benign	52

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
152556	GRCh38/hg38 18q12.3-21.1(chr18:43833480-46144138)x1	Pathogenic
156426	NM_004046.6(ATP5F1A):c.962A>G (p.Tyr321Cys)	Pathogenic
2572074	NM_004046.6(ATP5F1A):c.1252G>A (p.Gly418Arg)	Likely pathogenic
3329229	NM_004046.6(ATP5F1A):c.327G>C (p.Leu109Phe)	Likely pathogenic
429464	NM_004046.6(ATP5F1A):c.1176+1G>C	Likely pathogenic

SpliceAI

1907 predictions. Top by Δscore:

Variant	Effect	Δscore
18:46084248:A:C	donor_gain	1.0000
18:46084253:A:C	donor_gain	1.0000
18:46084501:TACC:T	donor_loss	1.0000
18:46084502:A:AC	donor_gain	1.0000
18:46084502:A:C	donor_loss	1.0000
18:46084503:C:CC	donor_gain	1.0000
18:46084650:GGGAG:G	acceptor_gain	1.0000
18:46084651:GGAG:G	acceptor_gain	1.0000
18:46084652:GAG:G	acceptor_gain	1.0000
18:46084652:GAGC:G	acceptor_loss	1.0000
18:46084653:AG:A	acceptor_gain	1.0000
18:46084653:AGCTG:A	acceptor_loss	1.0000
18:46084654:GCT:G	acceptor_loss	1.0000
18:46084655:C:CC	acceptor_gain	1.0000
18:46084655:C:CG	acceptor_loss	1.0000
18:46084663:A:AC	acceptor_gain	1.0000
18:46084663:A:C	acceptor_gain	1.0000
18:46086111:A:AC	donor_gain	1.0000
18:46086112:C:CA	donor_gain	1.0000
18:46086112:CA:C	donor_gain	1.0000
18:46086112:CAA:C	donor_gain	1.0000
18:46086112:CAAT:C	donor_gain	1.0000
18:46086112:CAATA:C	donor_gain	1.0000
18:46086116:A:AC	donor_gain	1.0000
18:46086116:ACTGT:A	donor_gain	1.0000
18:46086117:C:CC	donor_gain	1.0000
18:46086117:CTGTC:C	donor_gain	1.0000
18:46086120:T:A	donor_gain	1.0000
18:46086254:CTAC:C	acceptor_gain	1.0000
18:46086255:TACCT:T	acceptor_loss	1.0000

AlphaMissense

3564 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:46084612:C:T	G491D	1.000
18:46084613:C:G	G491R	1.000
18:46086142:A:G	L467P	1.000
18:46086151:C:A	G464V	1.000
18:46086151:C:T	G464D	1.000
18:46086152:C:A	G464C	1.000
18:46086152:C:G	G464R	1.000
18:46086154:C:G	R463P	1.000
18:46086172:G:A	T457I	1.000
18:46086181:T:A	D454V	1.000
18:46086182:C:A	D454Y	1.000
18:46086182:C:G	D454H	1.000
18:46086184:A:G	L453P	1.000
18:46086184:A:T	L453H	1.000
18:46086193:C:A	G450V	1.000
18:46086193:C:T	G450D	1.000
18:46086194:C:G	G450R	1.000
18:46086195:G:C	F449L	1.000
18:46086195:G:T	F449L	1.000
18:46086196:A:C	F449C	1.000
18:46086196:A:G	F449S	1.000
18:46086197:A:C	F449V	1.000
18:46086197:A:G	F449L	1.000
18:46086197:A:T	F449I	1.000
18:46086202:G:T	A447D	1.000
18:46086203:C:G	A447P	1.000
18:46086204:A:C	F446L	1.000
18:46086204:A:T	F446L	1.000
18:46086205:A:C	F446C	1.000
18:46086205:A:G	F446S	1.000

dbSNP variants (sampled 300 via entrez): RS1000076506 (18:46099448 T>TA), RS1000139005 (18:46103938 T>G), RS1000190457 (18:46104318 G>A), RS1000494593 (18:46092996 A>G), RS1000518284 (18:46088417 G>C), RS1000615255 (18:46101015 T>G), RS1000702453 (18:46095394 T>A), RS1000818456 (18:46095555 G>A), RS1000979736 (18:46080899 G>A), RS1000998590 (18:46084194 A>C), RS1001048159 (18:46101421 T>C), RS1001222815 (18:46088050 T>G), RS1001278583 (18:46103876 T>C), RS1001336178 (18:46097846 C>G,T), RS1001521247 (18:46092329 G>A)

Disease associations

OMIM: gene MIM:164360 | disease phenotypes: MIM:616045, MIM:620358, MIM:615228

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A	Strong	Autosomal dominant
mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B	Strong	Autosomal recessive
mitochondrial disease	Moderate	Autosomal recessive
mitochondrial proton-transporting ATP synthase complex deficiency	Supportive	Autosomal recessive
combined oxidative phosphorylation deficiency 22	Limited	Unknown

Mondo (6): combined oxidative phosphorylation deficiency 22 (MONDO:0020727), mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A (MONDO:0957254), mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B (MONDO:0014091), mitochondrial disease (MONDO:0044970), lactic acidosis (MONDO:0006040), mitochondrial proton-transporting ATP synthase complex deficiency (MONDO:0014471)

Orphanet (2): Isolated ATP synthase deficiency (Orphanet:254913), Mitochondrial disease (Orphanet:68380)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000089	Renal hypoplasia
HP:0000135	Hypogonadism
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000737	Irritability
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001285	Spastic tetraparesis
HP:0001298	Encephalopathy
HP:0001321	Cerebellar hypoplasia
HP:0001324	Muscle weakness

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006444_14	Bone mineral density (hip)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007702	hip bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000140	Acidosis, Lactic	C18.452.076.176.180

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2062351 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — F-type ATPase

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.83	Kd	1479	nM	CHEMBL3752910
5.83	ED50	1479	nM	CHEMBL3752910
5.76	Kd	1741	nM	CHEMBL5653589
5.76	ED50	1741	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 9 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147911: Binding affinity to human ATP5A1 incubated for 45 mins by Kinobead based pull down assay	kd	1.4790	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147911: Binding affinity to human ATP5A1 incubated for 45 mins by Kinobead based pull down assay	kd	1.7411	uM

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases reaction, affects expression, decreases expression	7
1-Methyl-4-phenylpyridinium	affects expression, decreases expression, increases expression, increases reaction	4
sodium arsenite	affects methylation, decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Atrazine	decreases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression, decreases expression	2
2,4,6-tribromophenol	decreases expression	1
bufotalin	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
IMOL S-140	increases expression	1
beta-lapachone	increases expression	1
3,3’-diindolylmethane	decreases reaction, increases expression	1
tetrabromobisphenol A	decreases expression	1
butylidenephthalide	increases expression	1
4-hydroxy-2-nonenal	affects binding	1
artenimol	affects binding	1
dibenzo(a,l)pyrene	decreases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
tanespimycin	affects cotreatment, increases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2065199	Binding	Binding affinity to ATP5A1 in human Jurkat cells at 150 uM followed by UV irradiation for 30 mins with Wood’s glass filtered medium pressure mercury arc light after cell lysis measured after denaturing wash by SDS-PAGE based pull down assay	Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9Y8	Ubigene HeLa ATP5F1A KO	Cancer cell line	Female

Clinical trials (associated diseases)

125 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00202228	PHASE4	COMPLETED	Lactate Metabolism Study in HIV Infected Persons
NCT01354652	PHASE4	TERMINATED	Lactic Acidosis During Entecavir(ETV)Treatment
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT00004490	PHASE3	COMPLETED	Phase III Randomized Study of Sodium Dichloroacetate in Children With Congenital Lactic Acidosis
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00004493	PHASE2	COMPLETED	Phase II Pilot Randomized Study of Sodium Dichloroacetate in Patients With Congenital Lactic Acidemia
NCT01973504	PHASE2	WITHDRAWN	Phase 2c Dose Comparison Study of MP4OX in Trauma
NCT02974257	PHASE2	TERMINATED	Thiamine vs. Placebo to Increase Oxygen Consumption After Cardiac Arrest
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT03122678	PHASE1	WITHDRAWN	Thiamine Supplementation in Patients With Septic Shock
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome