ATP5F1B

Summary

ATP5F1B (ATP synthase F1 subunit beta, HGNC:830) is a protein-coding gene on chromosome 12q13.3, encoding ATP synthase F(1) complex subunit beta, mitochondrial (P06576). Catalytic subunit beta, 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: 80.0% of cell lines).

This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing 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 beta subunit of the catalytic core.

Source: NCBI Gene 506 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited dystonia (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 60 total — 1 pathogenic
• Phenotypes (HPO): 13
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 80.0% of screened cell lines
• MANE Select transcript: NM_001686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:830
Approved symbol	ATP5F1B
Name	ATP synthase F1 subunit beta
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000110955
Ensembl biotype	protein_coding
OMIM	102910
Entrez	506

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 27 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000262030, ENST00000547250, ENST00000547808, ENST00000548474, ENST00000548647, ENST00000550162, ENST00000551020, ENST00000551182, ENST00000551570, ENST00000552959, ENST00000553007, ENST00000904666, ENST00000904667, ENST00000904668, ENST00000904669, ENST00000904670, ENST00000904671, ENST00000904672, ENST00000904673, ENST00000904674, ENST00000904675, ENST00000918318, ENST00000918319, ENST00000918320, ENST00000918321, ENST00000918322, ENST00000918323, ENST00000918324, ENST00000918325, ENST00000918326, ENST00000918327, ENST00000918328, ENST00000944727

RefSeq mRNA: 1 — MANE Select: NM_001686 NM_001686

CCDS: CCDS8924

Canonical transcript exons

ENST00000262030 — 10 exons

Exon	Start	End
ENSE00002405932	56638175	56638423
ENSE00003519814	56645171	56645353
ENSE00003551343	56639980	56640192
ENSE00003584533	56642458	56642580
ENSE00003648317	56639106	56639307
ENSE00003889097	56644781	56644955
ENSE00003893925	56643837	56643958
ENSE00003894245	56643403	56643587
ENSE00003894393	56642673	56642831
ENSE00003895138	56645837	56645984

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 461.9044 / max 3691.9412, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131565	455.5794	1828
131563	2.6999	1363
131561	2.3393	1348
131564	1.0936	673
131560	0.1921	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.88	gold quality
cardiac ventricle	UBERON:0002082	99.85	gold quality
heart left ventricle	UBERON:0002084	99.85	gold quality
right atrium auricular region	UBERON:0006631	99.80	gold quality
cardiac atrium	UBERON:0002081	99.79	gold quality
heart right ventricle	UBERON:0002080	99.77	gold quality
left ventricle myocardium	UBERON:0006566	99.76	gold quality
heart	UBERON:0000948	99.75	gold quality
cerebellar cortex	UBERON:0002129	99.75	gold quality
mucosa of transverse colon	UBERON:0004991	99.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.75	gold quality
cerebellar hemisphere	UBERON:0002245	99.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.73	gold quality
metanephros cortex	UBERON:0010533	99.72	gold quality
gastrocnemius	UBERON:0001388	99.71	gold quality
adult mammalian kidney	UBERON:0000082	99.68	gold quality
cerebellum	UBERON:0002037	99.68	gold quality
body of tongue	UBERON:0011876	99.68	gold quality
rectum	UBERON:0001052	99.67	gold quality
transverse colon	UBERON:0001157	99.66	gold quality
muscle of leg	UBERON:0001383	99.66	gold quality
prefrontal cortex	UBERON:0000451	99.65	gold quality
right adrenal gland	UBERON:0001233	99.65	gold quality
right adrenal gland cortex	UBERON:0035827	99.65	gold quality
renal medulla	UBERON:0000362	99.63	gold quality
left adrenal gland	UBERON:0001234	99.63	gold quality
right frontal lobe	UBERON:0002810	99.63	gold quality
myocardium	UBERON:0002349	99.62	gold quality
muscle organ	UBERON:0001630	99.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.61	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	1321.40
E-MTAB-9067	yes	22.91
E-HCAD-11	yes	20.18
E-MTAB-10042	yes	13.76
E-MTAB-8410	yes	13.67
E-HCAD-10	yes	12.05
E-HCAD-9	yes	8.35
E-MTAB-7606	no	2968.91
E-GEOD-124858	no	1067.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GABPA

miRNA regulators (miRDB)

18 targeting ATP5F1B, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-6789-5P	94.05	66.19	285

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis (PMID:12511957)
• Membrane-bound ATP synthase functions as a receptor for CF6 and may have a previously unsuspected role in the genesis of hypertension by modulating the concentration of intracellular hydrogen. (PMID:16230521)
• adenosine/uridine (AU)-rich element-binding proteins TIA-1 (T-cell intracellular antigen-1), TIAR (TIA-1-related protein), and HuR (Hu antigen R) interact with the beta-F1-ATPase mRNA through an AU-rich sequence located to the 3’-UTR. (PMID:16890199)
• This short review summarizes demonstrations of ATP5B (complex 5 of oxidative phosphorylation) subunit that show its movement under stereochemical alterations known to be induced during the binding of ADP and synthesis of ATP. (PMID:16927672)
• cholesterol exposure increased the level of ATPS-beta, along with Cav-1 and cholesterol in caveolae. the ectopic localization of ATPS-beta may participate in the energy balance of cells in response to the change in intracellular cholesterol levels. (PMID:16996794)
• conclude that ATP synthase beta-subunit may have an important role in the glucolipotoxicity of islet cells (PMID:18284036)
• Low levels of beta-F1-ATPase are sensitive to combined platinum and 2-deoxy-D-glucose treatment in ovarian carcinoma. (PMID:19567816)
• ATP synthase beta is phosphorylated at multiple sites and shows abnormal phosphorylation at specific sites in insulin-resistant muscle (PMID:20012595)
• Findings of the present study support the hypothesis that down-regulation of the bioenergetic activity of mitochondria in human tumours is exerted by translation silencing of beta-F1-ATPase mRNA. (PMID:20028336)
• Co-immunoprecipitation experiments in the presence of alpha-methyl mannose verified the binding of Escherichia coli FimH to ATP synthase beta-subunit of human brain microvascular endothelial cells. (PMID:20067530)
• Molecular and functional studies indicate that the interaction of G3BP1 with beta-F1 mRNA inhibits its translation at the initiation level, supporting a role for G3BP1 in the glycolytic switch that occurs in cancer. (PMID:20663914)
• Results suggested that the ectopic expression of ATP synthase is a consequence of translocation from the mitochondria. (PMID:20705594)
• Disturbed flow and hypercholesterolemia synergistically promote gamma/delta T-lymphocyte activation by the membrane translocation of ATPSbeta in endothelial cells. (PMID:21193741)
• Data suggest that F1-ATPase catalytic site show the correlation between the phosphate binding and the tightening of the alphabeta-interface. (PMID:21481781)
• Immunohistochemical analysis on a malignant mesothelioma tissue microarray showed cytoplasmic staining in 28 of 33 samples for vimentin and strong cytoplasmic staining in14 and weak in 16 samples for ss-F1-ATPase. (PMID:22022619)
• miR-127-5p targets the 3’UTR of beta-F1-ATPase mRNA (beta-mRNA) significantly reducing its translational efficiency. (PMID:22433606)
• Ectopic ATP synthase could be an accessible molecular target for inhibiting HIV-1 proliferation in vivo. (PMID:22753871)
• 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)
• Identification of ATP synthase as a lipid peroxide protein adduct in pancreatic islets from humans with and without type 2 diabetes mellitus. (PMID:23463654)
• H2O2 may induce melanogenesis via the upregulation of PAH and activation of cAMP/p-CREB/MITF signaling by increasing intracellular cAMP levels through the induction of ATP5B. (PMID:23523934)
• Mitochondrial ATPsyn-beta expression and ATP synthase activity in relapsed/refractory acute myeloid leukemia patients were downregulated. This downregulated expression exhibited a positive correlation with the response to adriamycin of primary cells. (PMID:24391795)
• ATP5B gene expressions were detected significantly higher in colorectal cancer samples. (PMID:24583174)
• No significant relationship was detected in the level of expression of the ATP2B4 and ATP5B genes in cancerous and healthy tissues of colorectal cancer patients. (PMID:24583174)
• Our study suggested that positive beta2M expression or loss of ATP5B expression in tumor tissues is closely related to the metastasis, invasion, and poor-prognosis of gallbladder cancer. (PMID:25311765)
• PKA phosphorylates the ATPase inhibitory factor 1 and inactivates its capacity to bind and inhibit the mitochondrial H(+)-ATP synthase. (PMID:26387949)
• High mRNA levels of ATP5B are associated with glioblastoma. (PMID:26526033)
• Hemoglobin - a novel ligand of hepatocyte ectopic F1-ATPase (PMID:26769832)
• Hypermethylation of ATPsyn-beta gene promoter is associated with a down-regulated mRNA expression and chemoresistance in AML patients. (PMID:26835708)
• experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired beta-F1-ATPase translation as an important consequence of obesity (PMID:27532680)
• These results suggested that increasing levels of ATP5B and ETFB were associated with worsening renal injury. (PMID:27840937)
• The results revealed that ATP5B expression is associated with the process of keratinocyte differentiation which may be related to intracellular ATP synthesis. (PMID:28209970)
• ATP5B, as a binding partner of a metastasis-related short peptide (B04) on prostate cancer cells, is involved in promoting prostate cancer metastasis. (PMID:28259978)
• In this instance, the ATP5B/CALR/HSP90B1/HSPB1/HSPD1-signaling network was revealed as the predominant target which was associated with the majority of the observed protein-protein interactions. As a result, the identified targets may be useful in explaining the anticancer mechanisms of ursolic acid and as potential targets for colorectal cancer therapy. (PMID:28347227)
• Results show that the relationship between ATPsyn-beta and insulin secretion deficiency suggests that ATPsyn-beta potentially could serve as a marker for type 2 diabetes mellitus disease risk in women with polycystic ovary syndrome. (PMID:28397049)
• findings show the T163S mutation affects the catalytic activity with a decrease in Ca2+-dependent and an increase in Mg2+-dependent ATP hydrolysis and desensitizes the permeability transition pore to Ca2+, resulting in increased resistance to Ca2+-dependent mitochondrial depolarization and to cell death (PMID:28507163)
• ATP5B reduction would be at least in part due to neuronal loss. (PMID:30539418)
• results shed light on the role of host proteins in RV genome assembly and particle formation and identify ATP5B as a novel pro-RV RNA-binding protein, contributing to our understanding of how host ATP synthases may galvanize virus growth and pathogenesis. (PMID:30770472)
• Data show that ectopic plasma membrane ATP5B denotes a high metastasis-risk phenotype in breast and prostate cancer, and a vulnerability of cancer cells in vivo. Across multiple datasets, ATP5B expression was significantly increased in the tumors relative to normal tissue, and negatively correlated with metastasis-free and overall survival. (PMID:31006104)
• 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)
• Identification and validation of suitable reference genes for quantitative real-time PCR gene expression analysis in pregnant human myometrium. (PMID:33386589)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp5f1b	ENSDARG00000070083
mus_musculus	Atp5f1b	ENSMUSG00000025393
rattus_norvegicus	Atp5f1b	ENSRNOG00000002840
drosophila_melanogaster	ATPsynbeta	FBGN0010217
caenorhabditis_elegans		WBGENE00000229

Paralogs (4): ATP6V1A (ENSG00000114573), ATP6V1B1 (ENSG00000116039), ATP6V1B2 (ENSG00000147416), ATP5F1A (ENSG00000152234)

Protein

Protein identifiers

ATP synthase F(1) complex subunit beta, mitochondrial — P06576 (reviewed: P06576)

Alternative names: ATP synthase F1 subunit beta

All UniProt accessions (6): P06576, F8W079, F8W0P7, H0YH81, H0YI37, V9HW31

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit beta, 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 subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain.

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 PPIF. 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 MTLN. Interacts with TTC5/STRAP; the interaction results in decreased mitochondrial ATP production.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2 (HUMOP2) [MIM:620085] A disorder apparent in infancy and characterized by euthyroid hypermetabolism, failure to thrive despite excessive caloric intake, intermittent hyperthermia, and developmental delay. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_001677* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000194	ATPase_F1/V1/A1_a/bsu_nucl-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR004100	ATPase_F1/V1/A1_a/bsu_N	Domain
IPR005722	ATP_synth_F1_bsu	Family
IPR020003	ATPase_a/bsu_AS	Active_site
IPR024034	ATPase_F1/V1_b/a_C	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036121	ATPase_F1/V1/A1_a/bsu_N_sf	Homologous_superfamily
IPR050053	ATPase_alpha/beta_chains	Family
IPR055190	ATP-synt_VA_C	Domain

Pfam: PF00006, PF02874, PF22919

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O + 4 H(+)(in) = ADP + phosphate + 5 H(+)(out) (RHEA:57720)

UniProt features (89 total): modified residue 20, binding site 19, strand 18, helix 18, sequence conflict 6, sequence variant 3, turn 2, transit peptide 1, chain 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-P06576-F1	85.72	0.67

Functional residue map

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

Ligand- & substrate-binding residues (19): 212; 212; 212; 213; 213; 213; 213; 214; 214; 238; 209; 239 …

Post-translational modifications (20): 124, 124, 133, 133, 161, 161, 198, 259, 259, 264, 264, 312, 415, 426, 433, 480, 485, 522, 522, 529

Glycosylation sites (1): 106

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-163210	Formation of ATP by chemiosmotic coupling
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
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: 325 (showing top): MYOGENIN_Q6, GOBP_RESPONSE_TO_PEPTIDE, MODULE_151, GCANCTGNY_MYOD_Q6, GCM_NPM1, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, REACTOME_FORMATION_OF_ATP_BY_CHEMIOSMOTIC_COUPLING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (14): angiogenesis (GO:0001525), osteoblast differentiation (GO:0001649), generation of precursor metabolites and energy (GO:0006091), lipid metabolic process (GO:0006629), ATP biosynthetic process (GO:0006754), negative regulation of cell adhesion involved in substrate-bound cell migration (GO:0006933), 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), regulation of intracellular pH (GO:0051453), cellular response to interleukin-7 (GO:0098761), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811), ATP metabolic process (GO:0046034)

GO Molecular Function (9): ATP binding (GO:0005524), MHC class I protein binding (GO:0042288), angiostatin binding (GO:0043532), metal ion binding (GO:0046872), proton-transporting ATP synthase activity, rotational mechanism (GO:0046933), proton-transporting ATPase activity, rotational mechanism (GO:0046961), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (14): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), mitochondrial membrane (GO:0031966), mitochondrial nucleoid (GO:0042645), proton-transporting ATP synthase complex (GO:0045259), extracellular exosome (GO:0070062), 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
Mitochondrial biogenesis	2
Protein localization	1
Aerobic respiration and respiratory electron transport	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
mitochondrion	4
cellular anatomical structure	3
proton motive force-driven ATP synthesis	2
intracellular membrane-bounded organelle	2
membrane protein complex	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
ossification	1
cell differentiation	1
metabolic process	1
primary metabolic process	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
substrate-dependent cell migration	1
negative regulation of cell adhesion	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
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
cellular response to cytokine stimulus	1
response to interleukin-7	1
monoatomic cation transmembrane transport	1
transport	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
MHC protein binding	1
protein binding	1
cation binding	1
proton channel activity	1
ligase activity	1
proton transmembrane transporter activity	1
ATPase-coupled monoatomic cation transmembrane transporter activity	1
ATPase activity, coupled to transmembrane movement of ions, rotational mechanism	1

Protein interactions and networks

STRING

5022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5F1B	ATP5F1C	P36542	998
ATP5F1B	ATPAF1	Q5TC12	969
ATP5F1B	ATP5F1D	P30049	965
ATP5F1B	ATP5F1E	P56381	956
ATP5F1B	ATPAF2	Q8N5M1	947
ATP5F1B	ATP5F1A	P25705	931
ATP5F1B	ATP5PO	P48047	845
ATP5F1B	SDHA	P31040	842
ATP5F1B	ATP5PD	O75947	838
ATP5F1B	ATP5PB	P24539	813
ATP5F1B	TMEM126B	Q8IUX1	794
ATP5F1B	ATP5PF	P18859	793
ATP5F1B	COX5A	P20674	776
ATP5F1B	TMEM126A	Q9H061	771
ATP5F1B	ACER3	Q9NUN7	769

IntAct

422 interactions, top by confidence:

A	B	Type	Score
ATPAF2	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.850
ATP5F1B	ATPAF2	psi-mi:“MI:0915”(physical association)	0.850
ATP5F1B	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.800
ATPAF1	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.740
ATP5IF1	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.740
ATP6V0C	ATP6AP2	psi-mi:“MI:0914”(association)	0.730
SLC19A2	ATP5F1B	psi-mi:“MI:0914”(association)	0.730
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
PRELID3B	TRIAP1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SLC35F1	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.690
ATP5F1B	ATP5PD	psi-mi:“MI:0915”(physical association)	0.670
ATP5PB	SLC19A2	psi-mi:“MI:0914”(association)	0.640
ACKR3	ATP5F1B	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
HTR1E	ATP5F1B	psi-mi:“MI:0914”(association)	0.560
ATP5F1B	BYSL	psi-mi:“MI:0915”(physical association)	0.560
LNX2	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.550
ATP5F1B	LNX2	psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530

BioGRID (860): ATP5B (Two-hybrid), ATP5B (Two-hybrid), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Co-fractionation), ATP5B (Two-hybrid), ATPAF2 (Two-hybrid), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5B (Affinity Capture-MS)

ESM2 similar proteins: A2C6Z4, A4YKE0, A5E950, A5GNB1, A7IH31, B5ZSN7, B6JD09, C0HK52, P00829, P00830, P05038, P06576, P10719, P17614, P19023, P22068, P23704, P29685, P37399, P38482, P42469, P46561, P49376, P56480, P83483, P83484, P99504, Q01859, Q05825, Q07UZ5, Q0C9L8, Q11DD5, Q13DP2, Q1MAZ2, Q1QQS8, Q25117, Q2J3I4, Q2RV18, Q3AZK5, Q3SVJ1

Diamond homologs: A0LDA0, A1B8P0, A1UR49, A3PIB9, A4WUM7, A4YKE0, A5E950, A5FZ54, A5V3X5, A5VSE1, A6UDM1, A6WXX1, A7HT52, A7IH31, A8F004, A8F2U0, A8GPZ4, A8GTS6, A8GY40, A8LJR4, A8MJV9, A9H9A8, A9IYW6, A9M837, A9WWS2, B0BVB6, B0T335, B3PQ68, B5ZSN7, B6JD09, B9LZ84, C0HK52, C3M9S1, C3PLT1, C4K227, O50290, P00829, P00830, P05038, P05440

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5F1B	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 204 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	30.3×	1e-06
Cristae formation	7	18.4×	1e-05
Mitochondrial biogenesis	10	12.7×	1e-06
Mitochondrial protein import	8	10.2×	9e-05
Mitochondrial protein degradation	10	8.7×	2e-05
Aerobic respiration and respiratory electron transport	12	8.1×	6e-06
Organelle biogenesis and maintenance	11	5.5×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	7	31.7×	1e-06
ubiquinone biosynthetic process	5	26.4×	3e-04
proton motive force-driven mitochondrial ATP synthesis	9	13.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1699953	NM_001686.4(ATP5F1B):c.1004T>C (p.Leu335Pro)	Pathogenic

SpliceAI

972 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56638419:TTCAC:T	acceptor_gain	1.0000
12:56638420:TCAC:T	acceptor_gain	1.0000
12:56638421:CAC:C	acceptor_gain	1.0000
12:56638421:CACC:C	acceptor_gain	1.0000
12:56638422:AC:A	acceptor_gain	1.0000
12:56638423:CC:C	acceptor_gain	1.0000
12:56638424:C:CC	acceptor_gain	1.0000
12:56638425:T:C	acceptor_loss	1.0000
12:56638428:A:C	acceptor_gain	1.0000
12:56638431:A:AC	acceptor_gain	1.0000
12:56638431:A:C	acceptor_gain	1.0000
12:56639100:TCTCA:T	donor_loss	1.0000
12:56639101:CTCAC:C	donor_loss	1.0000
12:56639102:TCA:T	donor_loss	1.0000
12:56639103:CA:C	donor_loss	1.0000
12:56639104:A:AC	donor_gain	1.0000
12:56639105:C:CC	donor_gain	1.0000
12:56639105:C:CT	donor_loss	1.0000
12:56639105:CCTG:C	donor_gain	1.0000
12:56639303:TAGTC:T	acceptor_gain	1.0000
12:56639304:AGTC:A	acceptor_gain	1.0000
12:56639305:GTC:G	acceptor_gain	1.0000
12:56639306:TC:T	acceptor_gain	1.0000
12:56639307:CC:C	acceptor_gain	1.0000
12:56639308:C:CA	acceptor_loss	1.0000
12:56639308:C:CC	acceptor_gain	1.0000
12:56639308:C:T	acceptor_gain	1.0000
12:56639310:A:AC	acceptor_gain	1.0000
12:56639310:A:C	acceptor_gain	1.0000
12:56639978:A:AC	donor_gain	1.0000

AlphaMissense

3408 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56639173:G:C	F474L	1.000
12:56639173:G:T	F474L	1.000
12:56639174:A:C	F474C	1.000
12:56639174:A:G	F474S	1.000
12:56639175:A:G	F474L	1.000
12:56639183:G:T	A471D	1.000
12:56639222:C:G	R458P	1.000
12:56639234:A:T	V454E	1.000
12:56639258:A:G	L446P	1.000
12:56639258:A:T	L446H	1.000
12:56639270:C:A	G442V	1.000
12:56639270:C:T	G442D	1.000
12:56639271:C:A	G442C	1.000
12:56639271:C:G	G442R	1.000
12:56639273:A:G	L441P	1.000
12:56639273:A:T	L441Q	1.000
12:56639276:A:C	I440S	1.000
12:56639276:A:G	I440T	1.000
12:56639276:A:T	I440N	1.000
12:56639279:G:T	A439D	1.000
12:56639280:C:G	A439P	1.000
12:56639282:A:C	I438S	1.000
12:56639282:A:T	I438N	1.000
12:56639294:A:G	L434P	1.000
12:56639984:A:G	L428P	1.000
12:56640059:G:A	S403F	1.000
12:56640077:G:T	A397D	1.000
12:56640080:G:C	P396R	1.000
12:56640080:G:T	P396Q	1.000
12:56640081:G:A	P396S	1.000

dbSNP variants (sampled 300 via entrez): RS1000934141 (12:56647665 C>T), RS1000965276 (12:56647492 A>C,G), RS1001121129 (12:56642141 G>A,C,T), RS1001423573 (12:56647201 G>T), RS1002123788 (12:56647014 C>G,T), RS1002196834 (12:56638502 C>T), RS1002863394 (12:56644127 C>T), RS1003662316 (12:56647303 C>A), RS1003771760 (12:56646011 G>A,C,T), RS1004442379 (12:56643115 C>A,T), RS1004940379 (12:56641519 A>C), RS1005397457 (12:56644413 C>T), RS1005477882 (12:56639272 C>A,T), RS1005607855 (12:56637998 T>A), RS1005741224 (12:56645723 C>T)

Disease associations

OMIM: gene MIM:102910 | disease phenotypes: MIM:620085, MIM:621502

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited dystonia	Moderate	Autosomal dominant
mitochondrial proton-transporting ATP synthase complex deficiency	Limited	Autosomal dominant
hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2	Limited	Autosomal dominant

Mondo (4): hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2 (MONDO:0859302), dystonia 38, susceptibility to (MONDO:0980989), mitochondrial proton-transporting ATP synthase complex deficiency (MONDO:0014471), inherited dystonia (MONDO:0044807)

Orphanet (0):

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001508	Failure to thrive
HP:0001954	Recurrent fever
HP:0001987	Hyperammonemia
HP:0002591	Polyphagia
HP:0002789	Tachypnea
HP:0003138	Increased blood urea nitrogen
HP:0003593	Infantile onset
HP:0004325	Decreased body weight
HP:0010910	Hypervalinemia
HP:0010911	Hyperleucinemia
HP:0010913	Hyperisoleucinemia
HP:0011342	Mild global developmental delay

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004611_187	High light scatter reticulocyte count	7.000000e-09
GCST004616_95	Platelet distribution width	1.000000e-67
GCST90002386_324	High light scatter reticulocyte percentage of red cells	2.000000e-14
GCST90002401_244	Platelet distribution width	9.000000e-10
GCST90002406_338	Reticulocyte fraction of red cells	6.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2062350 (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
6.05	Kd	882.4	nM	CHEMBL3752910
6.05	ED50	882.4	nM	CHEMBL3752910
5.64	Kd	2306	nM	CHEMBL5653589
5.64	ED50	2306	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	2147912: Binding affinity to human ATP5B incubated for 45 mins by Kinobead based pull down assay	kd	0.8824	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147912: Binding affinity to human ATP5B incubated for 45 mins by Kinobead based pull down assay	kd	2.3063	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Acetaminophen	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Rotenone	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
trichostatin A	affects expression, affects cotreatment, increases expression	1
sulforaphane	affects binding	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	increases expression	1
butylidenephthalide	decreases expression	1
brequinar	decreases expression	1
phenethyl isothiocyanate	affects binding	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
tanespimycin	decreases expression	1
K 7174	decreases expression	1
fenpyroximate	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
pyrachlostrobin	decreases expression	1
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide	decreases expression	1
STA 9090	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2065198	Binding	Binding affinity to ATP5B 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 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8ZR	Ubigene HEK293 ATP5F1B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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