ATP5F1A (ATP synthase F1 subunit alpha)

Gene

• Entrez ID: 498
• Gene name: ATP synthase F1 subunit alpha
• Gene symbol: ATP5F1A
• Synonyms (NCBI Gene): ATP5A, ATP5A1, ATP5AL2, ATPM, COXPD22, HEL-S-123m, MC5DN4, MC5DN4A, MC5DN4B, MOM2, OMR, ORM, hATP1
• Chromosome: 18
• Chromosome location: 18q21.1
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587776960	G>A	Pathogenic	Coding sequence variant, missense variant
rs587777788	T>A,C	Pathogenic	Coding sequence variant, missense variant
rs1131691396	C>G	Likely-pathogenic	Splice donor variant
rs1555695396	A>G	Pathogenic	Intron variant, splice donor variant

Transcription factors

Transcription factor	Regulation	Reference
USF2	Activation	10434034

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001937	Process	Negative regulation of endothelial cell proliferation	IMP	10077593
GO:0002020	Function	Protease binding	IEA
GO:0003723	Function	RNA binding	HDA	22658674
GO:0005515	Function	Protein binding	IPI	10077593, 11410595, 11741979, 15161933, 19285951, 19343720, 19688755, 20618440, 21106936, 22309213, 27499296, 28514442, 30021884, 32814053, 33961781
GO:0005524	Function	ATP binding	IBA
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	ISS
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IC	12110673
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	NAS	1830491
GO:0005743	Component	Mitochondrial inner membrane	IDA	19016746
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	NAS	26297831
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005886	Component	Plasma membrane	IDA	10077593
GO:0005886	Component	Plasma membrane	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006629	Process	Lipid metabolic process	ISS
GO:0006754	Process	ATP biosynthetic process	IEA
GO:0006754	Process	ATP biosynthetic process	IMP	21106936
GO:0006754	Process	ATP biosynthetic process	NAS	1830491
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0009986	Component	Cell surface	IEA
GO:0014850	Process	Response to muscle activity	IEA
GO:0015986	Process	Proton motive force-driven ATP synthesis	IBA
GO:0015986	Process	Proton motive force-driven ATP synthesis	IDA	37244256
GO:0015986	Process	Proton motive force-driven ATP synthesis	IEA
GO:0015986	Process	Proton motive force-driven ATP synthesis	NAS	26297831
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IDA	21106936
GO:0016020	Component	Membrane	IEA
GO:0016469	Component	Proton-transporting two-sector ATPase complex	IEA
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0032559	Function	Adenyl ribonucleotide binding	IEA
GO:0042288	Function	MHC class I protein binding	IDA	17643490
GO:0042776	Process	Proton motive force-driven mitochondrial ATP synthesis	IDA	12110673
GO:0043531	Function	ADP binding	IBA
GO:0043531	Function	ADP binding	IEA
GO:0043532	Function	Angiostatin binding	IPI	21106936
GO:0043536	Process	Positive regulation of blood vessel endothelial cell migration	IGI	21106936
GO:0045121	Component	Membrane raft	IEA
GO:0045259	Component	Proton-transporting ATP synthase complex	IBA
GO:0045259	Component	Proton-transporting ATP synthase complex	IDA	12110673, 21106936, 37244256
GO:0045259	Component	Proton-transporting ATP synthase complex	IEA
GO:0045259	Component	Proton-transporting ATP synthase complex	NAS	26297831
GO:0045471	Process	Response to ethanol	IEA
GO:0046034	Process	ATP metabolic process	IEA
GO:0046933	Function	Proton-transporting ATP synthase activity, rotational mechanism	IBA
GO:0046933	Function	Proton-transporting ATP synthase activity, rotational mechanism	IDA	12110673
GO:0046933	Function	Proton-transporting ATP synthase activity, rotational mechanism	IEA
GO:0046933	Function	Proton-transporting ATP synthase activity, rotational mechanism	IMP	21106936
GO:0046933	Function	Proton-transporting ATP synthase activity, rotational mechanism	ISS
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0071549	Process	Cellular response to dexamethasone stimulus	IEA
GO:0071732	Process	Cellular response to nitric oxide	IEA
GO:1902495	Component	Transmembrane transporter complex	IEA
GO:1902600	Process	Proton transmembrane transport	IEA

Other IDs

• MIM: 164360
• HGNC: 823
• e!Ensembl: ENSG00000152234

Protein

• UniProt ID: P25705
• Protein name: ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha)
• Protein 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
• PDB: 8H9E, 8H9I, 8H9L, 8H9P, 8H9S, 8H9T, 8H9U, 8H9V, 8KI3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02874	ATP-synt_ab_N	67 → 135	ATP synthase alpha/beta family, beta-barrel domain	Domain
  PF00006	ATP-synt_ab	192 → 415	ATP synthase alpha/beta family, nucleotide-binding domain	Domain
  PF00306	ATP-synt_ab_C	422 → 547	ATP synthase alpha/beta chain, C terminal domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Fetal lung, heart, liver, gut and kidney. Expressed at higher levels in the fetal brain, retina and spinal cord. {ECO:0000269|PubMed:8428659}.
• Sequence:

  MLSVRVAAAVVRALPRRAGLVSRNALGSSFIAARNFHASNTHLQKTGTAEMSSILEERIL
  GADTSVDLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSSGLKGMSLNLEPDNVGVVVFG
  NDKLIKEGDIVKRTGAIVDVPVGEELLGRVVDALGNAIDGKGPIGSKTRRRVGLKAPGII
  PRISVREPMQTGIKAVDSLVPIGRGQRELIIGDRQTGKTSIAIDTIINQKRFNDGSDEKK
  KLYCIYVAIGQKRSTVAQLVKRLTDADAMKYTIVVSATASDAAPLQYLAPYSGCSMGEYF
  RDNGKHALIIYDDLSKQAVAYRQMSLLLRRPPGREAYPGDVFYLHSRLLERAAKMNDAFG
  GGSLTALPVIETQAGDVSAYIPTNVISITDGQIFLETELFYKGIRPAINVGLSVSRVGSA
  AQTRAMKQVAGTMKLELAQYREVAAFAQFGSDLDAATQQLLSRGVRLTELLKQGQYSPMA
  IEEQVAVIYAGVRGYLDKLEPSKITKFENAFLSHVVSQHQALLGTIRADGKISEQSDAKL
  KEIVTNFLAGFEA

• Sequence length: 553

Pathways

KEGG:

Oxidative phosphorylation
Metabolic pathways
Thermogenesis
Alzheimer disease
Parkinson disease
Amyotrophic lateral sclerosis
Huntington disease
Prion disease
Pathways of neurodegeneration - multiple diseases
Chemical carcinogenesis - reactive oxygen species
Diabetic cardiomyopathy

Reactome:

Formation of ATP by chemiosmotic coupling
Cristae formation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Combined oxidative phosphorylation deficiency 22	Pathogenic; Likely pathogenic	rs587777788, rs1131691396	RCV000144489 RCV001809449	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lactic acidosis	Likely pathogenic; Pathogenic	rs1555695342	RCV001293385	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A	Likely pathogenic; Pathogenic	rs1412572728, rs1555695342	RCV003313764 RCV003226313	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMERS DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATP5F1A-related disorder	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL COMPLEX V DEFICIENCY, NUCLEAR TYPE 4A	—	ClinVar, Disgenet, GWAS catalog, HPO ClinVar, Disgenet, GWAS catalog, HPO ClinVar, Disgenet, GWAS catalog, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL COMPLEX V DEFICIENCY, NUCLEAR TYPE 4B	—	CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial disease	Conflicting classifications of pathogenicity	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Confusional Senile Dementia	Senile Dementia	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Early Onset	Alzheimer disease	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease, Focal Onset	Alzheimer disease	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	31086314		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	25842287, 26969910, 27623174, 31330218		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	23088660	Inhibit	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	30086823		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	29207195, 34520292	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	29207195	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood asthma	Asthma	BEFREE	20182505		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	27749317		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	35445138	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	19261598, 20709793, 24204606		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	24204606	Associate	★☆☆☆☆ Found in Text Mining only
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 22	Combined Oxidative Phosphorylation Deficiency	GENOMICS_ENGLAND_DG	23596069, 23599390		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 22	Combined Oxidative Phosphorylation Deficiency	UNIPROT_DG	23596069		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 22	Combined Oxidative Phosphorylation Deficiency	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 22	Combined Oxidative Phosphorylation Deficiency	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital hypoplasia of lung	Pulmonary hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	29738372		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	29207195		★☆☆☆☆ Found in Text Mining only
Depression, Postpartum	Mental Depression	BEFREE	29747048		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	3233232		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial Alzheimer Disease (FAD)	Alzheimer disease	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Frontotemporal dementia	Frontotemporal dementia	BEFREE	31086314		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	26526033		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	26526033		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	29738372		★☆☆☆☆ Found in Text Mining only
Idiopathic pulmonary arterial hypertension	Pulmonary arterial hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	27749317, 28855875		★☆☆☆☆ Found in Text Mining only
Isolated ATP synthase deficiency	Isolated ATP Synthase Deficiency	ORPHANET_DG	23599390		★☆☆☆☆ Found in Text Mining only
Isolated ATP synthase deficiency	Isolated ATP Synthase Deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Left Ventricular Hypertrophy	Left Ventricular Hypertrophy	BEFREE	31762174		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	24685647, 38066059	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	30538797		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	26526033		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	3233232		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4	Mitochondrial Complex Deficiency	GENOMICS_ENGLAND_DG	23596069, 23599390		★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4	Mitochondrial Complex Deficiency	UNIPROT_DG	23599390		★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4	Mitochondrial Complex Deficiency	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4	Mitochondrial Complex Deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	23596069	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial encephalopathy	Mitochondrial encephalopathy	BEFREE	23599390		★☆☆☆☆ Found in Text Mining only
Mitochondrial Respiratory Chain Deficiencies	Mitochondrial Respiratory Chain Deficiencies	BEFREE	23596069		★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	BEFREE	7811839		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19261598, 30538797		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	31482685		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	22134720, 23254161		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	36593912	Associate	★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	CTD_human_DG	19374891		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	30538797		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	BEFREE	31308681		★☆☆☆☆ Found in Text Mining only
Pulmonary arterial hypertension	Pulmonary arterial hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	16213148, 17918747, 25449713		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	LHGDN	19110265		★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	27816958, 29869623, 31201798		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	26238294		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	37482618	Associate	★☆☆☆☆ Found in Text Mining only
Testicular Neoplasms	Testicular neoplasm	Pubtator	30924599	Associate	★☆☆☆☆ Found in Text Mining only
Torsades de Pointes	Torsades de Pointes	BEFREE	29738372		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	34520292	Associate	★☆☆☆☆ Found in Text Mining only